Effect of endotoxin on phospholipids of hepatic mitochondria membrane and cation A antagonism in rabbits

AIM: To investigate the effect of endotoxin on phospholipid of hepatic mitochondria membrane (MiM) and cation A (CA) antagonism in the model of endotoxemia in rabbits. METHODS: Forty-eight healthy Japanese big-ear rabbits were randomly divided into 3 groups: the normal control (groupⅠ), endotoxin treatment group (groupⅡ) and cation A and endotoxin treatment group (group Ⅲ). The contents of phosphatidylcholine (PC), phosphatidylethanolamin (PE), phosphatidylserine (PS) and phosphatidylinositol (PI) in MiM of three groups were measured at the 3rd or 7th hour after corresponding treatment. RESULTS: The contents of the four phospholipids in groupⅡ were lower than those in groupⅠ during the experiment (P<0.01). A significant increase in the contents of four phospholipids in group Ⅲ was observed as compared to group Ⅱ (P<0.05, P<0.01). CONCLUSION: Endotoxin decreases the major membrane phospholipids in MiM, whereas CA has a prominent protective effect on injuries by endotoxin in MiM and provides a valuable evidence for the use of some drugs of endotoxin antagonist.     

Expression of ROCK I and TGF-β1 in pulmonary arterioles of rat with chronic thromboembolism pulmonary hypertension

AIM:To investigate the dynamic expression of Rho kinase (ROCK I) and transforming growth factor β₁ (TGF-β₁) in pulmonary arterioles of rat with chronic thromboembolic pulmonary hypertension. METHODS: Sixty-four male Wister rats were randomly divided into eight groups: beginning control group, embolism for 3 d, 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks groups and end control group. The pulmonary thromboembolism (PTE) model was established by injecting thrombin into jugular vein two times in two weeks and each rat underwent peritoneal injection with tranexamic acid one time a day during experiment to prevent thrombolysis. The mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI), relative medial thickness of small pulmonary arteries (PAMT) and vessel wall area/total area (WA/TA) were measured. The levels of ROCK I mRNA and TGF-β₁ protein in rat pulmonary artery were determined by in situ hybridization, immunohistochemistry and image analysis, respectively. RESULTS: mPAP, PAMT and WA/TA were higher respectively in embolism from 4 weeks group to 12 weeks group than those in beginning control group (mPAP: all P<0.01, PAMT and WA/TA: 4 weeks group P<0.05, 8 weeks group and 12 weeks group P<0.01). RVHI was elevated in 8 weeks group P<0.05, in 12 weeks group P<0.01. ROCK I mRNA and TGF-β₁ protein in pulmonary arterioles got the enhanced positive signals of in situ hybridization or immunohistochemistry staining with prolonging the time of rats with pulmonary thromboembolism. ROCKⅠ mRNA: embolism from 3 d group to 2 weeks group P<0.05, 4 weeks group to 12 weeks group P<0.01, TGF-β₁ protein: 1 week group and 2 weeks group P<0.05, 4 weeks group to 12 weeks group P<0.01. Linear correlation analysis showed that ROCK I mRNA and TGF-β₁ protein were positively correlated with mPAP, RVHI and vessel remodeling index (all P<0.01), ROCK I mRNA were positively correlated with TGF-β₁ protein (P<0.01). CONCLUSION:ROCK I and TGF-β₁ play a role in the pathogenesis of chronic thromboembolic pulmonary hypertension and pulmonary vessel remodeling. TGF-β₁ produces biological effect by active ROCK signal pathway.     

Effects of angiotensionⅡon metalloproteinases and matrix in hypertrophied myocardium from infarcted rats

AIM: To investigate the roles of angiotensionⅡ (AngⅡ) receptors (AT₁, AT₂) antagonists on matrix metalloproteinases (MMPs) and extracellular matrix (ECM) system in septal myocardium from infarcted rats.METHODS: The model of rat myocardium infarction (MI) was established by permanent ligation of the left coronary artery. The treatments of the AT₁ receptor antagonist valsartan (10 mg·kg^-1·d^-1) or AT₂ receptor antagonist PD123319 (30 mg·kg^-1·d^-1) were started 7 days prior to surgery. On day 14 after MI, protein levels of MMP-2, 3, 9, fibronectin (FN), tenascin-C (TN-C) in interventricular septum (IS) were determined. The distributions of FN and TN-C were also determined by immunofluorescence.RESULTS: Pathological changes of IS on day 14 after MI showed typical myocardial hypertrophy. Protein expressions of MMP-2, 3, 9 and TN-C of IS in banding group were higher than those in sham-operation group (P<0.01). The expressions of TIMP-1 and FN were lower than those in sham-operation group (P<0.01). Protein expressions of MMP-2, 3, 9 and TN-C in valsartan group were obviously lower than those in banding and PD123319 groups (P<0.01). TIMP-1 and FN protein expressions in valsartan group were higher than those in banding and PD123319 groups (P<0.01). No difference between banding and PD123319 groups was observed (P>0.05).CONCLUSION: AngⅡis involved in myocardium remodeling in infarcted rats, which is mediated via AT₁ receptor to degrade matrix by MMPs. The heart protection of AT₁ receptor antagonists may relate to inhibition of MMPs.     

Change of mitochondria during apoptosis in Jurkat cells induced by arsenic trioxide

AIM: To study the changes of mitochondria during apoptosis in Jurkat cells induced by arsenic oxide (As₂O₃). METHODS: By treated with 4×10^-6 mol/L As₂O₃, apoptosis and necrosis of Jurkat cells were assessed by annexin V-FITC/PI double staining flowcytometry. Mitochondrial mass and its membrane potential (△ψm) was measured by NAO/PI and DiOC₆ (3)/PI staining, respectively. Free radical formation was detected by DCFDA staining. RESULTS: After 48 h of As₂O₃ treatment, the rates of early apoptotic Jurkat cells in As₂O₃ and control groups were (18.98±1.40)% and (5.17±0.80)%, respectively (P<0.01). The necrotic rate in As₂O₃ group was significantly higher than that in control group (P<0.01), they were (8.56±0.70)% and (1.53±0.55)%, respectively. △ψm decreased Jurkat cells in As₂O₃ groups and control groups were (23.07±3.62)% and (6.63±1.46)%. The percentages of low mitochondrial mass cells in As₂O₃ and control groups were (25.90±1.80)% and (6.37±1.04)% (P<0.01). Intracellular free radicals in As₂O₃ group was increased, compared with control group, their DCFDA-fluorescence mean intensities were (24.41±0.75) and (17.06±0.48) (P<0.01). CONCLUSION: During apoptotsis process in As₂O₃-induced Jurkat cells, mitochondrial membrane potential and mitochondrial mass loses significantly, with increase in free radicals.     

Effects of Tongxinluo on expression of apoptotic factors in cerebral tissues of hypoxic preconditioned mice

AIM: To observe the effects of Tongxinluo (TXL), a Chinese medicine, on hypoxic tolerance and expression of Bcl-associated X (Bax) and B-cell leukemia/lymphoma 2 (Bcl-2) in hypoxia-preconditioned mice. METHODS: The mice were randomly divided into groups of hypoxia preconditioning without (control group) or with TXL treatment (TXL group). The mice in TXL group were administered with TXL at dose of 1.52 g·kg^-1·d^-1 crude drug for 5 days. The mouse was exposed to normoxia (0 run, H₀) and acute repetitive hypoxia for 1-5 runs (H₁-H₅) by placing the animal in an air-sealed jar. The hypoxic environment was established in the jar through consumption of the oxygen by the respiration of the mouse. A gasp breath was regarded as the hypoxic tolerant limit of the mouse and the animal was then transferred to another new jar. The mouse was exposed to hypoxia in this way for 5 times. In each run of hypoxic exposure, the time of hypoxic tolerance was measured. Western blotting was used to measure the protein levels of hypoxia inducible factor-1α (HIF-1α), Bax and Bcl-2 in the cerebral cortex. RESULTS: The hypoxic tolerance time in control and TXL groups was gradually increased run by run (P<0.01 or P<0.05). The protein levels of HIF-1α and Bcl-2 in the two groups were gradually increased (P<0.01 or P<0.05). Bax in control and TXL groups was significantly increased in H₁. After H₁, Bax was decreased run by run (P<0.01 or P<0.05). Compared with control group, the tolerance time, the expression of HIF-1α and Bcl-2 in the cerebral cortex in TXL group were increased in H₁,H₃ and H₅. However, the expression of Bax was lower than that in control group in every run. CONCLUSION: Hypoxia preconditioning makes the organism produce a strong adaptive response. The increase in Bcl-2 and the decrease in Bax may be involved in the mechanism of adaptation. TXL obviously increases the adaptive ability of the mice to hypoxia.     

Effect of angelica on myocardial fibrosis post myocardial infarction in rats

AIM: To investigate 1) the role of transforming growth factor-β₁ (TGF-β₁) and macrophage infiltration during the development of myocardial fibrosis (MF) in rats after myocardial infarction (MI);and 2) mechanisms of MF post-MI and the inhibitory effect of angelica.METHODS: Sprague-Dawley (SD) rats were subjected to MI by ligating the left anterior descending coronary artery.The animals were randomly divided into three groups: sham, MI and MI+angelica.After 24 hours of ligation, rats received angelica (20 mL·kg^-1·d^-1, ip) or saline.Left ventricular hemodynamics were measured and rats were killed at week 1, week 2 and week 4, respectively.Collagen content, macrophage infiltration and TGF-β₁ expression were examined in the non-infarcted area.RESULTS: ① In MI group, the numbers of macrophage and TGF-β₁ expression were significantly upregulated compared to sham at week 1 post-MI and remained elevated at week 4 (P<0.01).Angelica significantly decreased macrophage infiltration and TGF-β₁ expression (P<0.01 vs MI).② Collagen content was increased significantly in MI group compared to sham at week 2 and week 4 (P<0.01), and decreased in MI+angelica group (P<0.05 vs MI).③ Cardiac function was markedly decreased post-MI in MI group (P<0.01), and improved at week 4 in MI+angelica group (P<0.05).CONCLUSION: In MF post-MI, angelica may have an antifibrotic effect by decreasing macrophage infiltration and TGF-β₁ expression, by which reactive myocardial fibrosis is reduced, and cardiac function is improved.     

Mechanisms of PGF2α on the glucose-induced insulin secretion in NIT-1β cells

AIM:To investigate the cellular mechanisms by which PGF₂α promotes glucose-stimulated insulin secretion in NIT-1 beta cells. METHODS:Using the radioimmunoassay (RIA), the amount of the PGF₂α augmentation of glucose stimulated insulin secession was determined in different conditions, and the confocal laser scanning methods by Fluo-3AM as a fluorescent probe were used to analyze the changes of intracellular calcium in NIT-1β cells. RESULTS:At the lower glucose (0, 5.5 mmol/L), PGF₂α (5 μmol/L) failed to potentiate insulin secretion (P>0.05). However, in the presence of 16.5 mmol/L glucose, PGF₂α increased significantly in insulin secretion (P<0.05). Neither the AC inhibitor ddA nor the GC inhibitor Ly-83583 altered PGF₂α-potentiated insulin secretion in the presence of 16.5 mmol/L (P<0.05 or P<0.01). Otherwise, the PLC inhibitor U-73122 and the PKC blocker calphostin C both counteracted the insulinotropic of PGF₂α (P<0.01 or P<0.05). Moreover, exposure of the NIT-1β cells to 5 μmol/L PGF₂α induced a rapid increase of intracellular calcium (P<0.01). The inhibitor, ddA or Ly-83583 had no impact on PGF₂α-induced elevation of the intracellular calcium (P<0.01). Pretreatment of the cells with U-73122 completely prevented the calcium response induced by PGF₂α (P<0.01). CONCLUSION:Efects of PGF₂α was independent of cAMP or cGMP, potentiated glucose (16.5 mmol/L)-induced insulin secretion in NIT-1β cells through stimulation of phospholipase C, which subsequently mediated the elevation of intracellular calcium and activation of protein kinase C.     

Preventive effects of anti-IGFBPrP1 antibody on hepatic fibrosis in mice

AIM: To investigate the preventive effect and mechanism of anti-insulin-like growth factor binding protein related protein 1(IGFBPrP1) antibody on hepatic fibrosis induced by thioacetamide (TAA) in mice.METHODS: Twenty-four male C57BL/6 wild-type mice were randomly divided into 3 groups (n= 8 in each group): normal control group, TAA group (4 weeks) and TAA+anti-IGFBPrP1 antibody group (4 weeks). The morphological changes of liver tissues were observed. The expression levels of α-smooth muscle actin (α-SMA), transforming growth factor beta 1 (TGF-β₁), Smad3, phosphorylated Smad2/3 (p-Smad2/3), fibronectin (FN), collagen I, collagen Ⅲ and IGFBPrP1 were detected by the methods of immunohistochemistry and Western blotting.RESULTS: In TAA group (4 weeks), obvious injury of liver was observed, and the expression levels of α-SMA, TGF-β₁, Smad3, p-Smad2/3, FN, collagen Ⅰ, collagen Ⅲ and IGFBPrP1 were significantly increased as compared with normal control group (P<0.01). Compared with TAA group (4 weeks), the injury of the liver was alleviated and the expression levels of the proteins above were decreased in TAA+anti-IGFBPrP1 antibody group (4 weeks, P<0.01). IGFBPrP1 was positively correlated with TGF-β₁, Smad3, p-Smad2/3, FN and collagen I (P<0.01). CONCLUSION: Anti-IGFBPrP1 antibody prevents TAA-induced hepatic fibrosis in mice by inhibiting the activation of hepatic stellate cells, reducing the expression of p-Smad2/3 and inhibiting the TGF-β₁/ Smad3 signal transduction, thereby depressing the deposition of extracellular matrix in liver tissues.     

Calreticulin is involved in the protection of hypoxic preconditioning against cardiomyoblast H9c2 cell oxidative injury

AIM: To investigate whether hypoxic preconditioning (HPC) protects cardiomyoblast H9c2 cells against oxidative injury, and to discuss whether calreticulin (CRT) contribute to this protection through p38 MAPK signaling pathway. METHODS: Cardiomyoblast H9c2 cells were randomly divided into eight groups as follows: hydrogen peroxide stress (H₂O₂); brief hypoxic exposure of 20 min to simulate hypoxic preconditioning (HPC); 20 min of hypoxic exposure followed by 24 h of normoxic reoxygenation before hydrogen peroxide stress (HPC+H₂O₂), SB203580 (the specific inhibitors of p38 MAPK)+HPC+H₂O₂, antisense oligonucleotides transfection of calreticulin (AS), AS+H₂O₂, AS+HPC+H₂O₂ and control. Morphological studies, estimation of lactate dehydrogenase (LDH) leakage and flow cytometry were employed to assess the cell apoptosis and necrosis. RT-PCR and Western blotting analysis was used to detect calreticulin expression and phosphorylation of p38 MAPK. RESULTS: The results obtained are as follows: (1) HPC relieved cell injury caused by H₂O₂. Compared with those in H₂O₂ group, apoptosis rate and LDH leakage in culture medium in HPC + H₂O₂ group decreased 13.4% and 44.0%, respectively (P<0.05), and cell survive rate increased 12.7% (P<0.05). SB203580, a selective p38 MAPK inhibitor presented before HPC, eliminated the cytoprotection of HPC. Compared with HPC+H₂O₂ group, apoptosis rate and LDH leakage increased 5.4% and 45.0%, respectively (P<0.05), and cell survive rate decreased 5.0%(P<0.05). (2) Brief hypoxia intimating HPC resulted in mild CRT up-regulation (1.4-fold increased vs control group, P<0.05), but this up-regulation was lower than that of 3.6-fold increase induced by oxidative stress. HPC relieved the over-expression of CRT induced by H₂O₂ (26% decreased vs H₂O₂ group, P<0.05). (3) Transfection of antisense oligonucleotides of CRT before HPC reduced cytoprotection against oxidative stress. Correlative analysis indicated that mild up-regulation of CRT induced by HPC was positively correlated with survive rate (r=0.8573, P<0.05). (4) SB203580 suppressed CRT up-regulation (the expression of CRT decreased 38% or 23%, vs HPC+H₂O₂ group or HPC group, respectively). CONCLUSION: These results suggest that hypoxic preconditioning up-regulates calreticulin expression through p38 MAPK signaling pathway and protects cardiomyoblast H9c2 cells against oxidative injury.     

Characteristics of ventricular electrophysiology in a right ventricular rapid pacing-induced canine heart failure model

AIM: To research the characteristics of ventricular electrophysiology in right ventricular rapid pacing-induced congestive heart failure (CHF) dogs.METHODS: Dogs (n=16) were randomly divided into 2 groups: the control (n=7) and the CHF group (n=9) induced by rapid right ventricular pacing at 240 pulse·min-1 for 4 to 5 weeks.The electrophysiologic parameters were evaluated by the technique of standard electric stimulation and monophasic action potential (MAP) recording.RESULTS: (1) Ventricular effective refractory period (VERP),ventricular MAP duration (MAPD90),ventricular late repolarization duration (VLRD) and intra-ventricular conduction time (IVCT) were prolonged by 26% (P<0.01),43% (P<0.01),318% (P<0.05),and 19% (P<0.01),respectively in CHF group.(2)The ratio of VERP to MAPD₉₀ (VERP/MAPD₉₀) was decreased by 13% (P<0.05) in CHF group.(3) The dispersion of ventricular recovery time (VRT-D) was increased by 185% (P<0.01) in CHF group.(4) The ventricular fibrillation threshold (VFT) was decreased by 48% (P<0.01) in CHF group.CONCLUSION: The abnormal electrophysiological changes in the CHF condition may be contributing factors of lethal ventricular arrhythmias and sudden cardiac deaths in CHF.     

The Effect and mechanism of gestational estrogen and progesterone level on H-Y mismatched skin graft survival in murine model

AIM: To investigate the effect of estrogen(E₂) and progesterone(P₄) alone or applied together to H-Y skin graft and the potential mechanism.METHODS: The female C57BL/6 mice were ovariectomized and divided into four groups(n=12 in each). The mice were treated consecutively for 14 d with subcutaneous injection of saline, E₂ and P₄ alone or in combination, respectively. Before and after H-Y skin grafting, half mice of each group were sacrificed, and the CD4⁺CD25⁺Foxp3⁺ regulatory T cells of peripheral blood and the serum cytokines were detected by flow cytometry and ELISA, respectively. The skin graft survivals of the other half were observed.RESULTS: E₂ alone could significantly augment the proportion of regulatory T cells. In the presence of H-Y antigen, this effect was further enhanced(P<0.05). By contrast, P₄ had no effect on the expression of Foxp3, regardless of the presence of H-Y antigen or not(P>0.05). The effect of E₂ in combination with P₄ was similar to that of E₂ alone(P>0.05). The administration of sex hormone regardless of E₂ and P₄ alone or in combination, significantly decreased production of pro-inflammatory cytokines, but increased production of anti-inflammatory cytokines(P<0.05). The skin graft survivals were significantly prolonged in the different experimental groups compared to vehicle control group. E₂ and P₄ had a synergistic effect to prolong the skin graft survivals(P<0.05). CONCLUSION: E₂ and P₄ suppress the inflammatory response and enhance the regulatory response to exogenous antigen, through influencing the levels of cytokines and/or the proportion of regulatory T cells, which may contribute to induce the transplant tolerance.     

Roles of dendritic cells treated with 17β-estradiol in immune tolerance induction in skin allograft

AIM: To study the roles of bone marrow-derived dendritic cells from donor mouse treated with 17β-estradiol (E₂) in immune tolerance induction in skin allograft. METHODS: Bone marrow-derived dendritic cells from C57 mouse as donor were cultured respectively treated with E₂ (E₂ group). BALB/c mouse as recipient received respectively one injection of dendritic cells of E₂ group, mature dendritic cell group and immature dendritic cell group intravenously. Skin transplantation was performed in the absence of immunosupression after 7 d. Mice that received PBS were served as control. The time of skin survival was observed after transplantation. Flow cytometry was used to analyze the percentage of CD4+CD25+ T cells in peripheral blood respectively before and after transplantation. RESULTS: Compared with immature dendritic cells and control group, the time of skin survival in E₂ group was significantly longer (P<0.01), especially, the time of skin survival still prolonged 10.6 d after skin rejection in immature dendritic group. The percentage of CD4+CD25+ regulatory T cells in E₂ group was significantly higher than that in immature dendritic cell group and control group (P<0.01). CONCLUSION: In skin allograft model, dendritic cells treated with E₂ prolong the allograft survival time.     

Expression of TGF-β1 and Smad2/3 in kidney of STZ-induced diabetic nephropathy rats

AIM: To study the role of TGF-β/Smad pathway in the development of renal fibrosis in diabetic nephropathy.METHODS: Rats were induced to diabetic nephropathy by using tail intravenous injection of STZ.The expression of TGF-β₁, Smad2/3 protein and mRNA in kidney were examined at 2, 4, 8 and 16 weeks after STZ induction.CTGF, collagen-Ⅲ, PAI-1 mRNA expression in kidney at 16 weeks of STZ-induced diabetic nephropathy and normal rats were studied by RT-PCR.RESULTS: Weak TGF-β₁, Smad2/3 protein were detected in normal renal tissues while strong TGF-β₁, Smad2/3 staining were observed in renal tissues of diabetic nephropathy (0.057±0.030/0.223±0.040;0.017±0.010/0.153±0.010, respectively, P<0.05).The TGF-β₁, Smad2/3 protein expression were constantly high with the development of diabetic nephropathy and fibrosis (0.153±0.010, 0.122±0.050, 0.141±0.070 and 0.216±0.030 for 2, 4, 8 and 16 weeks, respectively).The TGF-β₁, Smad2 mRNA expression also increased with the development of diabetic nephropathy (2.86, 3.25 fold compared to control, respectively).The expression of TGF-β₁, Smad2, CTGF, collagen-Ⅲ and PAI-1 mRNA were significantly higher in kidney of 16 week diabetic nephropathy rats than that in normal ones (3.92, 2.95, 1.57, 1.95 and 1.97 folds compare to control, respectively, P<0.05).CONCLUSION: The results indicate that TGF-β₁/ Smad2 pathway activity might play an important role in pathophysiological process of diabetic nephropathy.It may be involved in diabetic renal fibrosis through up-regulation of CTGF and PAI-1 to promote extracellular matrix deposition.     

Effect of atorvastatin on HMG-CoA reductase expression in spontaneously hypertensive rats

AIM: To evaluate the effect of atorvastatin on HMG-CoA reductase (HMGR) expression level in spontaneously hypertensive rats (SHR). METHODS: Twelve eight-week-old SHR was randomized into distilled water group (SHR_DW group, n=6) and atorvastatin-treated group (SHR_ATV group, n=6). The age-matched Wistar-Kyoto rats (WKY) were used as control (WKY group, n=6). RT-PCR and Western blotting were used to detect HMGR mRNA and protein expression levels, respectively. Meanwhile, systolic blood pressure (SBP) and serum lipid levels were examined. RESULTS: Ten weeks a treatment, SBP in SHR_ATV group was markedly decreased compared with before treatment and SHR_DW group (P<0.05). The levels of TC, TG, LDL-C and HDL-C in SHR_ATV group were also markedly lower than those in SHR_DW group and WKYgroup (P<0.05). 10 weeks later, HMGR mRNA levels decreased markedly in SHR_ATV group compared to WKY group and SHR_DW group (P<0.05). The similar results were found in HMGR protein expression levels. CONCLUSIONS: Atorvastatin downregulates mRNA and protein expression levels of HMGR in SHR, which not only decreases the serum lipids levels, but also impacts blood pressure to a certain extent.     

The role of TGF-β signal protein Smad2/3 in tubulointerstitial fibrosis associated with unilateral ureteral obstruction in rats

AIM:To investigate the functional role of TGF-β₁ signal protein Smad2/3 in tubulointerstitial fibrosis associated with unilateral ureteral obstruction in rats. METHODS:The unilateral ureteral obstruction (UUO) model was induced by the ligation of left ureter. Rats were sacrificed at 1, 3, 7, 14, 21, and 28 days after UUO was initiated. TGFβ₁ protein, phosphorylated Smad2/3 and interstitial α-smooth muscle actin (α-SMA) expression were assayed by immunohistochemical staining. TGF-β1 mRNA in the obstructed kidney was analyzed with in situ hybridration. HE and Masson staining were used for histological and morphometric studies of the pathological change in obstructed kidney. RESULTS:The results showed that upregulation of TGF-β₁ in tubulointerstitium of both cortex and medulla at day 3 (a 3.1 fold increase vs control, P<0.05) when interstitial volume started to increase significantly. The highest expression of TGF-β1 was detected at day 7 (6.2 folds vs control, P<0.01). Phosphorylated Smad2/3, mainly detected in the nucleus of tubular cells, were also markedly upregulated at day 3 (a 3.5 fold increase vs control, P<0.05), and this was steadily increased by day 7 (7.8 folds vs control, P<0.01). The expression of interstitial α-SMA in both cortex and medulla was evident at day 3 (a 3.8 fold increase vs control, P<0.05) and peaked by day 7 (9.2 folds vs control, P<0.01). The deposit of extracellular matrix (ECM) and interstitial volume in renal cortex and medulla continued to increase until day 28 in obstructed kidney. CONCLUSION:These findings suggest that TGF-β₁ signal protein Smad2/3 may play an important role in tubulointerstitial fibrosis associated with unilateral ureteral obstruction in rats.     

Complement activation in acute coronary syndromes

AIM: To evaluate complement activation in patients with all forms of acute coronary syndromes (ACS) and to examine the relationship between the degree of complement activation and myocardial injury.METHODS: The subjects were divided into 2 groups: 110 ACS patients (group ACS) and 18 healthy persons (group control).One hundred and ten patients with ACS were divided into 3 sub-group: 51 patients with ST-segment elevated myocardial infarction (STEMI),28 patients with non-ST-segment elevated myocardial infarction (NSTEMI) and 31 patients with unstable angina (UA).Complement 3 (C₃),complement 4 (C₄),troponin T (TnT) as well as creatine kinase MB (CK-MB) were evaluated.RESULTS: Plasma C₃ and C₄ peak levels were significantly higher in patients with STEMI ［(1 525±302)mg/L and (423±123) mg/L］ and NSTEMI ［(1 516±289)mg/L and (396±68) mg/L］ than those in patients with UA ［(1 275±172)mg/L and (356±91) mg/L］ and the control subjects ［(1 072±196)mg/L and (182±73) mg/L］ (P<0.01 for all).Also,C₃ and C₄ serum levels in patients with UA were significantly higher than those in control subjects (P<0.01 for all).At one-week follow-up,plasma levels of C₃ and C₄ were significantly different among various days in patients with ACS (P<0.01).Plasma C₃ and C₄ levels in ACS showed a relationship with peak creatine kinase MB (CK-MB) and troponin T (TnT) levels (P<0.01).CONCLUSION: Plasma C₃ and C₄ levels are elevated in ACS in present study.The relationship between C₃,C₄ levels and ACS suggests that the complement activation is related to necrosis within the myocardium.