Effect of bone marrow-derived mesenchymal stem cells combined with vitamin E on inflammatory reaction in acute kidney injury

AIM:To explore the effect of bone marrow-derived mesenchymal stem cells (BMSCs) combined with vitamin E on the inflammatory reaction in acute kidney injury (AKI) rats. METHODS:Gentamicin was used to induce AKI and the rats were treated with BMSCs combined with vitamin E. After treatment, the rat plasma and kidney tissues were collected, and the expression of inflammatory factors at mRNA and protein levels was detected by real-time quantitative PCR and ELISA. RESULTS:After the treatment with BMSCs combined with vitamin E, the inflammatory proteins were down-regulated in the plasma and the renal tissues. Compared with single treatment group, the decreases in the inflammatory proteins were more obvious in combined treatment group. CONCLUSION: The method of BMSCs combined with vitamin E takes the anti-inflammatory effect on AKI, indicating a new and potential mode in clinical application for AKI therapy.     

Expression of NGAL in serum and renal tissues of patients with primary nephrotic syndrome and acute kidney injury

AIM: To observe the changes of neutrophil gelatinase-associated lipocalin (NGAL) level in serum and renal tissues of the patients with primary nephrotic syndrome (PNS) and acute kidney injury (AKI). METHODS: Seventy-two PNS patients were selected in the study and divided into 2 groups according to the pathological results of renal biopsy.The patients in PNS+AKI group included 15 cases of PNS with acute tubular necrosis (ATN), in which there were 10 cases of minimal change disease (MCD) with ATN and 5 cases of mesangial proliferative glomerulonephritis (MsPGN) with ATN. The patients in PNS alone group included 57 cases of PNS without ATN. According to the pathological types, they were divided into MCD group (24 cases), membranous nephropathy (MN) group (23 cases) and MsPGN group (10 cases). Serum samples from 15 healthy persons and 5 cases of normal renal tissues were used as controls. The serum levels of NGAL were detected by ELISA. The distribution and expression of NGAL in the renal tissues were observed by immunohistochemical method. RESULTS: (1) The serum level of NGAL in PNS alone group (including MCD group, MN group and MsPGN group) was significantly higher than that in normal control group. Compared with MCD group and MsPGN group, the serum level of NGAL in MN group increased significantly. The renal tissue positive expression index of NGAL in MCD group, MN group and MsPGN group was significantly higher than that in normal control group. (2) The serum level of NGAL and the renal tissue positive expression index of NGAL in MCD+ATN group and MsPGN+ATN group were significantly increased compared with PNS alone group. (3) The serum level of NGAL was positively correlated with 24 h urine protein, blood urea nitrogen and serum creatinine. No relation with serum albumin and β2 microglobulin was observed. The serum level of NGAL was positively correlated with the NGAL level in the renal tissue. CONCLUSION: The serum level of NGAL can be used as one of the sensitive indexes for early and non-invasive detection of PNS with AKI.     

Progress in genetic polymorphism and acute kidney injury

Acute kidney injury (AKI) is a frequent syndrome in hospitalized patients. Recently, a number of studies have been reported that the close relationship exists between genetic polymorphism and AKI. The current research on genetic polymorphism related with AKI is reviewed in this article.     

Relationship between apoptosis and change of P53 expression in mouse renal tissues after acute kidney injury

AIM: To investigate the relationship between renal cell apoptosis induced by ischemia/reperfusion injury and the activation of P53. METHODS: Eighteen mice were randomly divided into 3 groups: sham operation group, acute kidney injury (AKI) group and pifithrin-alpha(PFT-α) treatment group. The AKI model was established by clamping bilateral renal arteries for 45 min and then performing reperfusion. The mice in PFT-α group were intraperitoneally injected with PFT-α at dose of 2.2 mg/kg 5 min before AKI model was established. The changes of serum creatinine and urea nitrogen were determined and renal pathological changes were observed 48 h after AKI. The P53 expression in the kidney was evaluated by Western blotting and immunofluorescence methods. Apoptosis of the renal cells was observed by TUNEL assay. The protein expression of tumor necrosis factor receptor (TNFR), caspase-3 and Bcl-2 was detected by immunohistochemical method. RESULTS: The levels of serum creatinine and urea nitrogen in AKI group and PFT-α group were higher than those in sham operation group. Compared with AKI group, the levels of serum creatinine and urea nitrogen were significantlydecreased in PFT-α group. No pathological change of the kidney was observed in sham operation group. In AKI group, the pathological changes such as shedding of brush border, vacuolus and dropwise degeneration in the renal tissues were observed. These pathological changes were attenuated in PFT-α group as compared with AKI group. The protein was expression level of P53 and the apoptotic cells were much higher in AKI group than those in sham operation group, and P53 protein was mainly expressed in the renal cortex, while those were significantly decreased in PFT-α group as compared with AKI group. Compared with sham operation group, the expression levels of TNFR and caspase-3 were increased and the Bcl-2 levels was decreased. Compared with AKI group, the expression level of TNFR and caspase-3 decreased and Bcl-2 expression was increased. CONCLUSION: P53 protein is mainly expressed in the renal cortex and induces apoptosis by increasing the expression of caspase-3 and regulating the expression of TNFR and Bcl-2 in the kidney following ischemia/reperfusion injury.     

Effects of pulse high-volume hemofiltration on serum concentration of moxifloxacin in patients with continuous renal replacement therapy

AIM: To study the changes of the serum moxifloxacin concentration in the patients with continuous renal replacement therapy when applied for pulse high-volume hemofiltration (PHVHF). METHODS: The patients applied for PHVHF were intravenously given moxifloxacin at the dose of 400 mg in 60 min. Blood samples were collected from the arterial (input) and venous (output) lines of the extracorporeal circuit immediately at different time points after the beginning of infusion, and replacement fluid was taken at the corresponding time points. The serum concentration of moxifloxacin was measured by high-performance liquid chromatography (HPLC). The pharmacokinetics parameters were determined using DAS 2.1.1 software.RESULTS: Two-compartment model was used to achieve the best concentration-time relation of moxifloxacin. The levels of blood urea nitrogen (BUN), serum creatinine (SCr) and serum K⁺ were obviously decreased after application of PHVHF (P<0.05). The peak serum concentration (C_max) of moxifloxacin was (4.843±1.854) mg/L. The half-life (T_1/2) was (4.822±2.126) h and the peak time (T_max) was (1.31±0.59) h. The total volume of distribution (V_d) was (82.63±24.69) L. The total clearance (CL_tot) was (14.36±8.43) L/h. All the ratios of area under the concentration-time curve (AUC) to 90% minimal inhibitory concentration (MIC₉₀) were more than 100 when the values of MIC₉₀ were 0.25 mg/L, 0.12 mg/L and 0.03 mg/L. All the values of C_max/MIC₉₀ were more than 10 when the values of MIC₉₀ were 0.25 mg/L, 0.12 mg/L and 0.03 mg/L.CONCLUSION: Application of PHVHF obviously improves the renal functions and eliminates a part of moxifloxacin in the serum. However, the serum concentration of moxifloxacin remains at the effective level for controlling the pathogenic bacteria.     

Apoptosis of hepatocytes induced by acute kidney injury in rats

AIM: To observe the cytological changes of hepatocytes undergoing apoptosis induced by acute kidney injury (AKI) in rats. METHODS: The rat models of AKI, including ischemic and non-ischemic AKI, were established. Western blotting, immunohistochemical staining, light and electron microscopy were used in this study. RESULTS: Cellular necrosis in renal tubules, as the basic morphological changes of ischemic AKI, and renal tubular cells undergoing apoptosis were evident in ischemic AKI. Meanwhile, tumor necrosis facotor receptor α (TNFRα) and caspase-3 was strongly expressed in the livers from AKI rats. Caspase-3-positive cells were evident in the livers from AKI rats. Microscopic examinations revealed that hepatocytes undergoing apoptosis and para-apoptosis were observed in damaged livers of both ischemic and non-ischemic AKI animals. No significant difference of hepatic apoptosis between ischemic and non-ischemic AKI animals was observed. CONCLUSION: Either apoptosis, caspase-dependent cell death or para-apoptosis are involved in hepatic injury induced by AKI. TNFRα initiation and cleaved caspase family are the pathways of hepatocytes undergoing apoptosis induced by AKI.     

Liquid resuscitation combined with hydrogen inhalation reduce acute kidney injury during septic shock in rats

AIM: To investigate the therapeutic effects of a novel fluid resuscitation protocol (early fluid resuscitation plus 2% hydrogen inhalation) on acute kidney injury during septic shock induced by lipopolysaccharide (LPS) in rats.METHODS: Male Wistar rats were randomly divided into 4 groups (15 rats per group):control group, septic shock group, septic shock with early fluid resuscitation group (fluid group) and septic shock with early fluid resuscitation plus 2% hydrogen inhalation group (fluid+H₂ group). The rats were ventilated, and a 2% hydrogen mixture was used in fluid+H₂ group. LPS (10 mg/kg) was administered to establish the septic shock model in rats and fluid resuscitation was performed in fluid group and fluid+H₂ group.RESULTS: Fluid resuscitation with 2% hydrogen inhalation decreased the le-vels of serum creatinine, blood urea nitrogen and neutrophil gelatinase-associated lipocalin. It also reduced oxidative stress injury and decreased renal tumor necrosis factor-α and interleukin-6 levels compared with fluid resuscitation alone.CONCLUSION: Early fluid resuscitation plus 2% hydrogen inhalation provided more protection against acute kidney injury du-ring septic shock.     

Effect of inhaled nitric oxide on aquaporin expression in newborn rat lung in acute hyperoxic lung injury

AIM:To investigate the effect of inhaled nitric oxide on aquaporin expression and alveolar epithelial fluid transport in newborn rats with acute hyperoxic lung injury. METHODS:32 newborn SD rats were randomized to breathe for 48 h room air (C), >95%O₂ (O), >95%O₂+10^-5 NO (NO only in the first 24 h, ONO), room air + NO (CN). Then, the rats were killed, the lung wet-to-dry weight ratio (Q_W/Q_D), the histology, and AQP1, AQP5, α₁-NKA, α-ENaC mRNA expressions in the lungs were measured. RESULTS:Compared with C group, the Q_W/Q_D in O group significantly increased (P<0.01), and AQP1 mRNA expression decreased significantly (P<0.01). Compared with O group, ONO group had a lower level of Q_W/Q_D (P<0.05), and AQP1 mRNA expression increased (P<0.05). AQP5 mRNA expression in all groups remained unchanged. CONCLUSION:In newborn rats with acute hyperoxic lung injury, inhaled 10-5 nitric oxide for 24 h may attenuate lung edema and increase AQP1 mRNA expression, suggesting that inhaled 10^-5 nitric oxide for 24 h may promote the AQP1 expression in lung in this model of acute lung injury.     

Effect of taurine on kidney injury induced by paraquat poisoning in rats

AIM:To study the effects of taurine at different doses on renal oxidative stress and inflammation induced by paraquat in rats.METHODS:Male SD rats (n=48) were randomly divided into 4 groups:negative control group,paraquat group,paraquat+low-dose taurine group,and paraquat+high-dose taurine group.The serum levels of creatinine and urea nitrogen were detected by a biochemical analyzer.The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured by colorimetry.The plasma concentrations of IL-6 and intercellular adhesion molecule (ICAM)-1 were detected by ELISA.Renal reactive oxygen species (ROS) was checked by fluorescence probe dihydroethidium (DHE).The protein levels of renal p-P38 MAPK,p-ERK1/2 and p-JNK were determined by Western blot.The mRNA expression of TNF-α,IL-6 and TGF-β1 was detected by real-time PCR.RESULTS:Serum creatinine and urea nitrogen increased after paraquat poisoning,and decreased after feeding with taurine in poisoned rats,with better result in high-dose taurine group.Taurine reduced the oxidative stress and inflammation in the renal tissue,and also reduced the protein levels of p-JNK,p-ERK1/2 and p-P38 in the kidney of paraquat-poisoned rats.CONCLUSION:Taurine attenuates renal injury induced by paraquat poisoning in rats.The mechanism may be related to reducing renal MAPK activity,oxidative stress and inflammatory response.     

Role of PI3K/Nrf2 signaling pathway in endotoxin-induced acute kidney injury in rabbits

AIM: To evaluate the role of phosphatidylinositol 3-kinase/nuclear factor E2-related factor 2 (PI3K/Nrf2) signaling pathway in endotoxin-induced acute kidney injury in rabbits. METHODS: Healthy male New Zealand white rabbits were randomly divided into 5 groups: control group (group C), LPS group (group L), wortmannin+LPS group (group WL), wortmannin group (group W) and dimthyl sulfoxide (DMSO) group (group D). Wortmannin at dose of 0.6 mg/kg was injected via the auricular vein in groups W and WL, DMSO at concentration of 0.08 mL/kg was injected in group D, while normal saline (0.08 mL/kg) was injected in groups C and L. LPS at dose of 5 mg/kg was injected via the auricular vein in groups L and WL 30 min later, and equal volume of normal saline was injected in group C, D and W for control. The rabbits were sacrificed 6 h after LPS or normal saline administration. The kidneys were removed for microscopic examination and the determination of histological scores of kidney (HSK). The concentrations of blood urea nitrogen (BUN) and creatinine (Cr), urinary α1-microglobulin (α1-MG), MDA content, SOD activity, the mRNA expression of Nrf2 and HO-1, and the protein levels of total Akt, p-Akt, total Nrf2, p-Nrf2, nuclear Nrf2 and HO-1 in the renal tissues were also detected. RESULTS: Compared with groups C, D and W, the concentrations of BUN and Cr, urinary α1-MG concentration, MDA content and HSK were significantly increased, while SOD activity was significantly decreased (P<0.05). The mRNA expression of Nrf2 and HO-1, and the protein levels of p-Akt, total Nrf2, p-Nrf2, nuclear Nrf2 and HO-1 in the renal tissues were significantly increased in groups L and WL. No significant change among groups C, D and W was observed. Compared with group L, the concentrations of BUN and Cr, urinary α1-MG concentration, MDA content and HSK were significantly increased, while SOD activity, the mRNA expression of Nrf2 and HO-1, and the protein levels of p-Akt, total Nrf2, p-Nrf2, nuclear Nrf2 and HO-1 in the renal tissues were significantly decreased in group WL. CONCLUSION: Activation of PI3K/Nrf2 signaling pathway may be one of the regulatory mechanisms of the body adapting to the endotoxin-induced acute kidney injury in rabbits.     

Changes of pulmonary apoptosis and NOS mRNA in the lipopolysaccharide-induced acute lung injury

AIM: To observe the chronological changes of pulmonary apoptosis and the expression of iNOS mRNA,nNOS mRNA and eNOS mRNA in lipopolysaccharide (LPS)-induced acute lung injury (ALI) and to investigate the mechanisms of ALI.METHODS: Rats were randomly divided into 2 groups: control group and LPS treated group.The rats were injected with either saline or LPS and killed at 1,3,6,9 and 12 h after LPS injection.The expressions of iNOS mRNA,nNOS mRNA and eNOS mRNA in the lung tissue were respectively measured with RT-PCR methods.Apoptosis and expressions of Bcl-2 and Bax were respectively determined by flow cytometry (FCM) and immunohistochemistry (IHC).The pathological changes of lung tissue were observed under light and electron microscope.RESULTS: Compared with that in control group,the expression of iNOS mRNA was significantly increased at 3,6,9 and 12 h after administration of LPS (P<0.05).The eNOS mRNA was significantly decreased at 3,6,9 and 12 h after administration of LPS (P<0.05).The nNOS mRNA had no significant change during the 12 h in LPS group.Degree of ALI was gradually worsened after administration of LPS.Apoptosis of pulmonary cells was significantly increased,and reached the top level at 9 h after administration of LPS (P<0.01).The expression of Bcl-2 was markedly decreased and the expression of Bax was significantly enhanced in alveolar and airway epithelial cells in LPS treated group.CONCLUSION: The expressions of iNOS mRNA,eNOS mRNA and nNOS mRNA are not identical in LPS-induced acute lung injury.NOS regulates the apoptosis of pulmonary cells through affecting the balance of Bcl-2 and Bax.     

Effects of oxidative stress and inflammatory response on kidney injury in mice with hyperthyroidism

AIM To explore the effects of oxidative stress and inflammatory response on kidney injury induced by hyperthyroidism in mice. METHODS Forty male Kunming mice were randomly divided into control group （n=20） and L-thyroxine （T4） group （n=20）. The mice in T4 group were intraperitoneally injected with T4 diluent at a dose of 1 mg/kg to induce hyperthyroidism, and those in control group were injected with normal saline of the same volume. After 7 weeks, the mice were weighed and dissected, the kidneys were removed and weighed, and the length of tibia was also measured. The activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） in the kidney tissues were detected. The pathological changes of the kidney tissues were observed by HE staining. The levels of 4-hydroxynonenal （4-HNE）-modified proteins, interleukin-1 receptor-associated kinase 1 （IRAK1） and tumor necrosis factor receptor-related factor 6 （TRAF6） were determined by Western blot and immunohistochemistry. RESULTS Compared with control group, the body weight of the mice was decreased, while the kidney size and weight were increased significantly in T4 group. In addition, the ratios of kidney weight/body weight and kidney weight/tibia length were also increased （P<0.05）. In T4 group, the renal tubules were enlarged, and the epithelial cells of renal tubules were swollen and exfoliated, with vacuolar degeneration. Furthermore, reduced SOD activity, and increased MDA content and 4-HNE-modified proteins were found in T4 group, all of which were related to oxidative stress （P<0.05）. The levels of inflammation-related proteins IRAK1 and TRAF6 were significantly increased in T4 group （P<0.05）. CONCLUSION Excessive T4 may lead to kidney hypertrophy and injury in mice, and the mechanism may be related to oxidative stress and inflammatory response.     

Effect of black fungus extract on acute renal failure in rats

AIM：To investigate the effect of the extract of black fungus on acute renal failure (ARF) induced by injection of cisplatin in rats. METHODS：Thirty-two healthy male Wistar rats were randomly divided into 4 groups (n=8)：control group, model group, black fungus group and niaoduqing group. The mRNA expression of endothelin-1 (ET-1) was detected by RT-PCR. Blood urea nitrogen (BUN) and creatinine (Cr) in serum were measured. The blood gas was also analyzed. RESULTS：Compared with model group and niaoduqing group, the mRNA expression of ET-1, BUN and serum Cr in control group and black fungus group increased obviously (P<0.05). No significant difference between control group and black fungus group was observed (P>0.05). The results of blood gas analysis indicated that there were compensatory disorders of acid-base balance in black fungus group. CONCLUSION：The extract of black fungus may improve the renal function by influencing the production and release of vasoactive substance, and the extract also regulates the balance of electrolyte and acid-base balance.     

Protective effect of recombinant human serum albumin-thioredoxin fusion protein on mice with acute lung injury induced by influenza virus

AIM To investigate the protective effect of recombinant human serum albumin (HSA)-thioredox?in (Trx) fusion protein (HSA-Trx) on mice with acute lung injury (ALI) induced by influenza virus infection. METH?ODS: The recombinant HAS-Trx fusion protein was generated by Pichia pastoris expression system. ICR mice were used to establish the animal model of ALI induced by PR8 (H1N1) influenza virus, and the experimental mice were divided into healthy control group, ALI group, ALI+Trx group and ALI+HSA-Trx group, with 10 mice in each group. The bronchoalveolar lavage fluid (BALF) in each group was collected, the total number of cells and the number of alveolar neutrophils were determined, the protein concentration was measured by Coomassie brilliant blue solution method, and the interferon-γ (IFN-γ) content in BALF was detected by ELISA. The lung tissues were collected for hematoxylin and eosin staining. The inducible nitric oxide synthase (iNOS), 8-hydroxydeoxyguanosine (8-OHdG) and 3-nitrotyrosine (NO₂-Tyr) in lung tissues were detected by immunofluorescence method. Peroxide concentration in plasma was evaluated using a CR2000RC analyzer. RESULTS HSA-Trx treatment significantly reduced the total number of cells, neutrophils and total protein in BALF of ALI mice (P<0.05), and decreased the levels of 8-OHdG, NO₂-Tyr in lung tissue and peroxide in plasma (P<0.05). However, it has no significant inhibitory effect on iNOS and IFN-γ expression (P>0.05). CONCLUSION HSA-Trx inhibits inflammatory response and excessive production of nitric oxide in the lung, thus protecting influ?enza virus-induced ALI mice.     

Effect of microRNA-7 knockdown on ConA-induced acute liver injury in mice

AIM: To study the effect of microRNA-7 (miR-7) knockdown (KD) on concanavalin A (ConA)-induced acute liver injury (ALI) in mice.METHODS: Wild type (WT) mice and miR-7KD mice were received ConA (30 mg/kg) to induced acute liver injury model by intraperitoneal injection, and the morphological changes, liver weight and weight index were measured 48 h later. The pathological changes of the liver tissues were observed by HE staining. The levels of serum alanine aminotransferase (ALT), IL-4 and IFN-γ were detected by ELISA. The proportional changes of CD4⁺ T cells and the relative levels of IL-4 and IFN-γ were analyzed by flow cytometry.RESULTS: The color of the liver tissue became lighter, and the weight and weight index were changed significantly in miR-7KD mice compared with control group (P<0.05). HE staining showed that the inflammatory cell infiltration was increased in the liver of miR-7KD mice. Moreover, the level of serum ALT was significantly increased (P<0.05). The serum level of IFN-γ elevated significantly (P<0.01), while the IL-4 levels decreased significantly (P<0.01) in the serum of miR-7KD mice. Furthermore, the proportion of CD4⁺ T cells and relative IFN-γ cells increased obviously (P<0.01).CONCLUSION: miR-7 knockdown promotes the pathogenesis of the ConA-induced acute liver injury in mice.     

Expression of urotensin II and its receptor in nephridial tissues of rats with acute renal damage

AIM: To observe the mRNA expression of urotensin II (UII) and its receptor (G protein-coupled receptor 14,GPR14) in nephridial tissues of rats with acute renal damage. METHODS: Male Wistar rats were divided into 2 groups: the rats in control group (n=10) were administered with normal saline by gavage; the rats in model group (n=30) were administered with Caulis Aristolochiae manshuriensis (CAM) by gavage for 25 d to induce acute renal damage. Every 5 rats in model group were sacrificed on the 3rd, 7th, 15th and 25th days during CAM treatment and all rats in the 2 groups were killed 10 d after withdraw of CAM. The kidneys were collected for pathological observation and the UII and GPR14 mRNA examination.RESULTS: The degeneration, necrosis and disintegration in tubules were observed as major pathological changes in the rat kidneys after 3 d of CAM administration. The pathological changes were aggravated following the duration of in CAM administration, and were remained and even worsen when CAM was withdrawn for 10 d. Compared with control group, the mRNA expression of UII was significantly elevated (P<0.05) at the time point of CAM administration for 15 d,even obviously increased (P<0.01) at the time point of CAM administration for 25 d, and remained at the highest levels to the end of the observation. The mRNA expression of GPR14 was significantly increased (P<0.05) at the time point of CAM administration for 7 d, became higher (P<0.01) on the 15th day, and gradually increased as the experimental time went on. CONCLUSION: The mRNA levels of UII and its receptor are significantly elevated in CAM-induced renal lesion in rats, suggesting that UII plays a pathological role in the development of acute renal damage.     

Effects of different ventilation strategies on gas exchange and extravascular lung water during early stage of acute lung injury in a canine model

AIM: To evaluate the effects of different ventilation strategies on gas exchange and extravascular lung water during early stage of acute lung injury (ALI). METHODS: Upon the establishment of oleic acid-induced ALI (diagnostic standard: PaO₂/FiO₂ ≤ 300 mmHg), 24 adult mongrel dogs were randomly divided into 3 groups (n=8 each) according to different ventilation strategies: controlling high-concentration oxygen therapy (O₂) group, continuous positive airway pressure (CPAP) group and bi-level positive airway pressure (BiPAP) group. The parameters of gas exchange and hemodynamics including the values of normal baseline, at ALI early stage (positive control) and from 1 to 4 h after treatment were recorded continuously. RESULTS: Compared with the value at the beginning of ALI, after 4 h of artificial ventilation, the improvement in oxygenation index (PaO₂/FiO₂) in BiPAP group (375.83±81.55, P<0.01) and CPAP group (327.17±78.82, P<0.01) were better than that in O₂ group (255.00±49.85, P>0.05). The ratio of alveolar dead space to tidal volume [V_D(alv)/V_T]in O₂ group further increased (P<0.01), while it obviously declined in CPAP group and BiPAP group (P<0.01). Oxygen delivery (DO₂) in BiPAP group (P<0.01) was much higher than that in CPAP group and O₂ group, while oxygen consumption (VO₂) and oxygen extraction rate (O₂ER) in O₂ group were evidently higher than those in CPAP group and BiPAP group (P<0.05, P<0.01). After treatment, the alveolar-arterial oxygen differences [P_(A-a)O₂] of the 3 ventilation groups were significantly higher than the normal baseline values and the values at early ALI stage (P<0.01). BiPAP and CPAP greatly reduced the ratio of shunted blood to total perfusion (Qs/Qt) as compared with O₂ group (P<0.01). Some parameters including pulmonary arterial wedge pressure (PAWP) and index of cardiac output (CI) kept stable, while mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) further increased in CPAP group and BiPAP group (P<0.05,P<0.01). Three ventilation strategies did not effectively control the increase in extravascular lung water index (ELWI). CONCLUSION: During early stage of ALI, BiPAP and CPAP make active effects on improving gas exchange and tissue oxygenation. BiPAP displays more significant therapeutic effect than CPAP and oxygen therapy. The 3 ventilation strategies have no obvious effects on reducing extravascular lung water.     

Effect of IL-13 on expression of IL-1β in acute renal ischemia/ reperfusion injury in rats

AIM:To investigate the effects of IL-13 on expression of IL-1β in acute renal ischemia/reperfusion injury.METHODS:Fifty-seven male Wistar rats were randomly divided into 8 group: normal group, sham operation group, ischemia group, ischemia/reperfusion injury group(I/R), normal saline(NS)-treated group 1(C-1), NS-treated group 2(C-2), IL-13-treated group1(T-1)and IL-13-treated group 2(T-2).Rats were subjected to 45 min bilateral renal ischemia followed by reperfusion. rmIL-13 (1.5 μg/50 g body weight )was injected into the renal arteries through the abdominal aorta before ischemia(T-1) or immediately afterischemia(T-2).The serum level of IL-1β and the renal expression of IL-1β were determined in each group at 24 h post-ischemia. In addition, BUN, Cr and renal histology were also measured.RESULTS:(1)The serum level of IL-1β, gene expression and protein production of IL-1β in kidney decreased markedly in IL-13-treated groups.(2)Renal function and histology were significantly improved in IL-13-treated groups, renal injury scores decreased significantly.(3)A positive correlation were found between the serum level of IL-1β and BUN, SCr(r=0.708, P＜0.01;r=0.770, P＜0.01).CONCLUSION:These data suggest that IL-13 inhibit the expression of IL-1βand improve func-tion and histology of kidney in acute renal ischemia/reperfusion injury.     

Effect of resveratrol on autophagy and renal interstitial fibrosis in kidney of diabetic mice

AIMTo observe the effect of resveratrol (Res) on renal autophagy level and renal interstitial fibrosis in the mice with diabetes mellitus (DM), and to discuss the possible mechanism. METHODSThe wild-type C57BL/6 mice were randomly divided into 3 groups, including normal control (NC) group, DM group and Res group (8 in each group). The diabetic mouse model was established by injection of streptozotocin. After 8 weeks of successful replication of the diabetic model, Res was given to the mice in Res group by continuous gavage for 12 weeks, and then the mice in each group were sacrificed to detect the relevant biochemical parameters. The pathological changes of the kidney tissues were observed by HE staining and Masson staining. The levels of the proteins related to autophagy, epithelial-mesenchymal transition (EMT) and fibrosis were determined by Western blot. The mRNA expression of collagen type IV (Col IV), α-smooth muscle actin (α-SMA) and E-cadherin were detected by real-time PCR. RESULTSCompared with NC group, fasting blood glucose (FBG), kidney index (KI), serum creatinine, 24-hour urinary albumin excretion rate and 24-hour urine total protein were remarkably increased in DM group (P<0.05). The results of HE and Masson staining indicated that renal tissue presented fibrosis in DM group. The protein levels of E-cadherin, beclin-1, microtubule-associated protein 1 light chain 3-II (LC3-II) were reduced in DM group, while the levels of α-SMA, Col IV and Snail1 were increased (P<0.05). After intervention with Res for 12 weeks, all the relevant biochemical parameters and KI were reduced (P<0.05) except FBG (P>0.05), and renal fibrosis lesions were obviously alleviated. Compared with DM group, the protein levels of E-cadherin, beclin-1 and LC3-II were increased in Res group, but the protein expression levels of α-SMA, Col IV, Snail1 were reduced (P<0.05). Compared with DM group, the mRNA level of E-cadherin was increased in Res group , but the mRNA levels of Col IV and α-SMA were reduced (P<0.05). CONCLUSION Resveratrol significantly inhibits EMT and reduces renal interstitial fibrosis in diabetic mice, and its mechanism may be related to the promotion of renal autophagy.