Captopril exerts myocardial protective effect in coronary microembolization rats by inhibiting oxidative stress injury and alleviating inflammatory response

AIM: To investigate the effects of captopril (CAP) on oxidative stress injury and inflammatory response induced by coronary microembolization (CME) and its related molecular mechanisms. METHODS: The rat model of CME was established by clamping the rat artery and injecting blood microemboli. The rats were divided into control group, CME group and CME+CAP group, with 6 rats in each group. The myocardial tissues of each group were collected. The changes of myocardial structure and the degree of inflammatory response were analyzed by HE staining. Cardiomyocyte apoptosis was detected by TUNEL staining. The fluorescence intensity of cleaved caspase-3 was detected by immunofluorescence obervation. The protein levels of cleaved caspase-3 and Bax were determined by Western blot. The activity of superoxide dismutase (SOD) and catalase was measured by ELISA. The production of reactive oxygen species (ROS) was detected by DHE fluorescence staining. RESULTS: CAP significantly reduced the myocardial structural changes (P<0.05), inflammatory cell infiltration (P<0.01), number of apoptotic cardiomyocytes (P<0.01), the protein levels of cleaved caspase-3 and Bax (P<0.01), and ROS production levels (P<0.01), but promoted the activity of antioxidant markers SOD and catalase (P<0.01) in the CME rats.CONCLUSION: CAP attenuates CME-induced myocardial injury by resisting oxidative stress and alleviating inflammatory response.     

Liraglutide attenuates hyperhomocysteinemia-induced oxidative stress and inflammatory response in rat hippocampus via p38 MAPK signaling pathway

AIM: To investigate the protective effect of liraglutide (Lir), an analog of glucgon-like peptide-1 (GLP-1), on hyperhomocysteinemia (Hhcy)-induced hippocampal pathological injury and the underlying molecular mechanisms in rats. METHODS: Sprague-Dawley rats (n=40) were randomly divided into 5 groups:control (Ctrl) group, model (Hhcy) group, low-dose Lir treatment (Lir-L) group, medium-dose Lir treatment (Lir-M) group and high-dose Lir treatment (Lir-H) group. The protein levels of p-p38, p-ERK1/2, p-JNK, immunoglobulin heavy chain binding protein (BIP) and C/EBP homology protein (CHOP) were determined by Western blot and immunohistochemical staining. The activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH), and the content of malondialdehyde (MDA) were measured. The expression levels of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) were examined by ELISA. RESULTS: Hhcy increased the levels of p-p38, BIP, CHOP, MDA, IL-1β, IL-6 and TNF-α,and reduced the activity of SOD and GSH, while simultaneous administration of Lir dose-dependently attenuated the Hhcy-induced oxidative stress and inflammatory responses, accompanied with the inhibition of p38 MAPK signaling pathway. CONCLUSION: Lir ameliorates Hhcy-induced oxidative stress and inflammatory injury in rat hippocampi with the mechanisms involving suppression of p38 MAPK pathway.     

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.     

Effects of Chinese herbal compound Huannaoyicongfang on inflammatory cytokines and oxidative stress in brain of APP transgenic mice

AIM: To study the effects of Chinese herbal compound Huannaoyicongfang (HNYCF) on inflammatory reaction and oxidative stress in the brain of Alzheimers disease (AD) animal model, and to explore its role in treating AD. METHODS: APP695V717I transgenic mice (3 months old),as an AD model in this study, were randomly divided into model group, donepezil group, HNYCF high-dose group and HNYCF low-dose group. C57BL/6J mice, which were of the same age and genetic background as the transgenic mice, were used as controls. The animals were administered intragastrically with the drug or water from 3 months old to 9 months old. Morris water maze test was performed to measure the spatial learning and memory ability. Step-down test was performed to observe the learning and memory ability of single passive avoidance response. The expression of nuclear factor kappa B (NF-κB) and peroxisome proliferator-activated receptor γ (PPARγ) in hippocampus CA1 region was detected by immunohistochemistry with image analysis. The levels of interleukin-6 (IL-6) and high sensitivity C-reactive protein (hs-CRP) in the brain cortex and hippocampus homogenate were measured by radioimmunoassay. The activity of superoxide dismutase (SOD) in serum was detected by colorimetry. The content of malondialdehyde (MDA) in serum was detected by thibabituric acid method. RESULTS: Morris water maze test showed that the times of crossing platform, and the swimming time and distance in the fourth quadrant in HNYCF groups were much more than those in model group. The step-down test manifested that the escape latency in HNYCF high-dose group was significantly longer than that in model group. Compared with model group, the expression of NF-κB obviously decreased, the expression of PPARγ significantly increased and the content of IL-6 was lower in HNYCF groups. The activity of serum SOD in HNYCF groups was significantly higher than that in model group. CONCLUSION: HNYCF evidently ameliorates the learning and memory ability in APP transgenic mice, which may be related to the anti-inflammatory and anti-oxidation effects of HNYCF.     

Dependence of adrenoceptor regulation on oxidative stress in cardiac injury induced by high sympathetic activity in rats

AIM：To investigate the dependence of the adrenoceptor regulation on oxidative stress in the rats with cardiac injury induced by high sympathetic activity. METHODS：Healthy SD rats were randomly divided into 7 groups: control, model, propranolol (Pro), prazosin (Praz), Pro+Praz, vitamin E (VE) and Pro+Praz+VE. The rats were intraperitoneally injected with norepinephrine (NE) for continuous 16 d to reproduce cardiac injury, and treated with the respective drugs. During the experimental process, the body weight was recorded. At the end of the experiments, the following parameters were measured: the ventricular remodeling indexes (cardiac index and hydroxyproline of the left ventricle), histopathologic examination, oxidative/antioxidative indexes ［MDA, SOD, catalase (CAT), GSH-Px and total antioxidant capacity (T-AOC)］, and energy metabolism (Na+-K+ ATPase and Ca2+-Mg2+ATPase). RESULTS：The increase of body weight in model group was significantly slower than that in control group after 9 d of treatment (P<0.05). The cardiac index and left ventricular hypertrophy were significantly increased. Oxidation/antioxidation and energy metabolism were disturbed. In Pro, Praz, Pro+Praz and VE groups, the body weight, cardiac index, left ventricular fibrosis and oxidative/antioxidative dysfunction were ameliorated. Pro, Praz and Pro+Praz increased the activity of Na+-K+ ATPase and Ca2+-Mg2+ATPase. Treatment with Pro+Praz showed the best result in all of the indexes (P<0.05). CONCLUSION：The dependence of adrenoceptor regulation plays an important role in the formation of oxidative stress in the process of rat cardiac injury induced by high sympathetic activity.     

An oxidative injury model of human kidney epithelial cells

AIM: To establish an injured cell model using human kidney proximal tubule epithelial cell line (HKC) to mimic the oxidative injury by hydrogen peroxide (H₂O₂). METHODS: The cell viability, the content of malondialdehyde (MDA) in the culture supernatant and the activity of intracellular superoxide dismutase (SOD) were detected to investigate the degree of cell injury. Osteopontin (OPN) expressed on the cell membrane surface were observed by laser confocal microscopy before and after cell injury. The changes of cellular morphology and the ultrastructure of membrane surface were observed under scanning electronic microscope. RESULTS: After HKC cells were treated with H₂O₂ at the concentration of 1 mmol/L for different time, the cell viability and the activity of SOD decreased and the content of MDA increased. The expression level of OPN significantly increased and reached to maximae at 1 h. The injured cells appeared shriveled and rough surface, and the shedding of most flagellae was also observed. CONCLUSION: H₂O₂ induces severer injury in HKC cells, including not only the cell viability and membrane surface ultrastructure, but also the OPN expression on the membrane, which could bind calcium oxalate crystal. Therefore, treatment with H₂O₂ at the concentration of 1 mmol/L for 1 h can be used to establish an oxidative injury model in HKC cells.     

Effects of astragaloside on the levels of sex hormone and oxidative stress injury in rats with polycystic ovary syndrome

AIM To investigate the effects of astragaloside on the levels of sex hormone and oxidative stress in rats with polycystic ovary syndrome （PCOS）. METHODS Female SD rats （n=60） were randomly divided into normal control group, model group, Diane-35 （0.339 2 mg/kg） group, low dose astragaloside （12.5 mg/kg） group and high dose astragaloside （50 mg/kg） group, with 12 rats in each group. The PCOS model was induced by letrozole （1 mg/kg）, which was administered by gavage once a day for 3 weeks. After administration, the estrus cycle of the rats was observed by vaginal smear, and the ovarian index was calculated. HE staining was used to observe the histopathological changes of the ovaries. Serum levels of the sex hormones testosterone （T）, estradiol （E₂）, luteinizing hormone （LH） and follicle-stimulating hormone （FSH） were measured by ELISA. The levels of superoxide dismutase （SOD）, malondialdehyde （MDA） and glutathione peroxidase （GSH-Px） in serum and ovarian tissue were detected by colorimetry, and the protein levels of steroidogenetic acute regulatory protein （StAR） and apoptosis-related proteins cleaved caspase-3, Bax and Bcl-2 in ovarian tissue were detected by Western blot. RESULT Compared with control group, the oestrous cycle of the rats in model group was disorder, and the ovarian index was increased, ovary was polycystic. The serum levels of T, LH and MDAwere significantly increased （P<0.05）, while the contents of E2, FSH and the activities of GSH-Px and SOD were significantly decreased （P<0.05）. The levels of MDA, StAR, cleaved caspase-3 and Bax proteins in ovarian tissue were significantly up-regulated （P<0.05）. GSH-Px and SOD activities and Bcl-2 protein levels were significantly down-regulated （P<0.05）. CONCLUSION Astragalosideeffectively balances the levels of sex hormone in PCOS rats and relieves the oxidative stress injury, the mechanism may be related to the inhibition of StAR expression.     

Protective effect of senegenin on retinal ganglion cells in oxidative stress induced injury

AIM: To evaluate the effect of senegenin (Sen) on H₂O₂-treated retinal ganglion cells (RGCs) and to explore its underlying mechanisms. METHODS: RGCs were retrograde labeled by injection of fluorogold into the superior colliculi of SD rats on the postnatal day 3. On the postnatal days 6 to 8, the retinas were dissociated with papain and cultured. Primary RGCs cultured in vitro were treated with H₂O₂ and/or various doses of Sen. The viability of RGCs was evaluated by counting the fluorescence-labeled neurons under microscope. The morphological changes of the nuclei in the retinal neurons were observed by Hoechst 33258 staining. Western blotting was applied to determine the expression of cleaved caspase-3, cytochrome C and Bcl-2 in cultured retinal neurons. RESULTS: Compared with the control cells, Sen at doses of 10, 20 or 40 μmol/L had no toxicity to RGCs (P>0.05). However, Sen at doses of 80 and 160 μmol/L had significant toxicity to RGCs (P<0.01). Compared with H₂O₂-injured group, Sen at doses of 10, 20 and 40 μmol/L effectively protected against H₂O₂-induced injury in RGCs (P<0.05) with the best efficiency at 40 μmol/L. Hoechst 33258 staining showed that the neuronal apoptosis caused by H₂O₂ was reduced by Sen. The results of Western blotting showed an up-regulation of Bcl-2, and decreased cytochrome C and cleaved caspase-3 levels by Sen in H₂O₂-treated retinal neurons. CONCLUSION: Sen is able to protect RGCs from H₂O₂-induced injury by enhancing Bcl-2 expression and inhibiting cell apoptosis.     

Clonidine inhibits inflammatory response in lung injury mice through cholinergic anti-inflammatory pathway

AIM:To explore the influence of clonidine on inflammatory response in lung injury mice and its possible mechanism.METHODS:Clonidine solution was intravenously injected into the mice with lung injury induced by LPS.The left upper lobe of the lung was collected to detect lung wet/dry weight ratio (W/D) and total lung water content (TLW).The concentrations of IL-6,IL-1β and TNF-α were measured by ELISA.The expression of α7 nicotinic acetylcholine receptor (α7nAChR) and high-mobility group box protein 1(HMGB1) at mRNA and protein levels was determined by RT-PCR and Western blot.After importing α7nAChR siRNA lentiviral vector or injecting exogenous HMGB1 protein,the inflammatory cytokines were detected.RESULTS:Clonidine attenuated lung injury and inhibited inflammatory reaction.Clonidine promoted the activation of cholinergic anti-inflammatory pathway by promoting α7nAChR expression.Clonidine inhibited HMGB1 expression,which promoted the secretion of IL-6,IL-1β and TNF-α.HMGB1 was negatively regulated by α7nAChR.CONCLUSION:Clonidine functions as an anti-inflammatory reagent to the lung injury mice.The mechanism may be related to activating the cholinergic anti-inflammatory pathway and inhibiting the expression of HMGB1.     

Effects of glutamine pretreatment on intestinal ischemia-reperfusion injury in rats

AIM：To determine the effects of glutamine (Gln) pretreatment on intestinal ischemia-reperfusion (I/R) injury in the rats. METHODS：Thirty male Wistar rats were randomly divided into 3 groups (n=10): sham group, I/R group and Gln pretreatment group. The rats in Gln pretreatment group were pretreated with 1 g·kg-1·d-1 Gln by orogastric route for 7 d, the rats in the other 2 groups were pretreated with normal saline. Intestinal I/R was induced by 30-min occlusion of the superior mesenteric artery followed by 24 h of reperfusion. After the operation, the plasma endotoxin, serum D-lactic acid, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured. The intestinal mucosal injury was observed with HE staining and evaluated using Chius scoring. RESULTS：Serum D-lactic acid, endotoxin level, MDA level and Chiu's score in I/R group were significantly higher than those in sham group and Gln group (all P<0.05). Serum SOD activity was significantly lower than that in sham group and Gln group (P<0.05). CONCLUSION：Glutamine has a protective effect on the intestines during ischemia-reperfusion injury. The mechanism may be related to oxidative stress response.     

Suramin alleviates hypertrophic scar in mice by inhibiting fibroplasia and inflammatory response

AIM: To investigate the therapeutical effect of suramin on hypertrophic scar (HPS) and its mechanism. METHODS: After the mouse model of HPS was established by mechanical stretching, the suramin solution at low dose (5 mg/kg) and high dose (10 mg/kg) was applied onto the scar site caused by mechanical load in mice by transdermal administration once a day for 10 d. The degree of scar hyperplasia was observed by macroscopy. The scar cross-sectional area and scar elevation index in the HPS tissues were evaluated by hematoxylin-eosin (HE) staining. The expression levels of transforming growth factor-β1 (TGF-β1) and interleukin-6 (IL-6) in HPS tissues were detected by immumohistochemical staining. The expression level of α-smooth muscle actin (α-SMA) in HPS tissues was detected by immunofluorescence staining, RT-qPCR and Western blot. The levels of tumor necrosis factor-α (TNF-α), IL-6, IL-10 and TGF-β1 in the HPS tissues were measured by ELISA. RESULTS: Macroscopic observation showed that the surface areas of scar in the HPS mice after treatment with suramin at low and high doses were significantly reduced (P<0.01). HE staining results showed that the scar cross-sectional area and the scar elevation index of HPS mice after treatment with suramin at low and high doses were significantly reduced (P<0.05 or P<0.01). The results of immunofluorescence staining, RT-qPCR and Western blot showed that the number of α-SMA positive cells and the mRNA and protein expression of α-SMA in scar tissues of HPS mice after treatment with suramin at low and high doses were significantly decreased (P<0.05 or P<0.01). The results of immunohistochemical staining showed that the expression levels of TGF-β1 and IL-6 in scar tissues of HPS mice after treatment with suramin at low and high doses were significantly reduced (P<0.01). The results of ELISA showed that the levels of TNF-α, IL-6, IL-10 and TGF-β1 in the scar tissues of HPS mice after treatment with suramin at low and high doses were significantly reduced (P<0.01). CONCLUSION: Suramin inhibits the formation of HPS, which may be related to the inhibition of fibroplasia and reduction of local inflammatory response.     

Effects of imidapril on blood gas,oxidative stress and inflammatory factors in rats with acute lung injury induced by ammonium chloride

AIM: In this study, the rat lung injury model was induced by ammonium chloride for studying the effect of imidapril on blood gas, serum TNF-α, IL-6 and MDA concentrations, and AngⅡ and CD54 protein expression in rat lung tissue. METHODS: Male rats were randomly divided into 3 groups: control group, lung injury model group and drug group. The rats in control group were given saline (2 mL/kg), while the rats in lung injury model group were given 6% ammonium chloride (2 mL/kg). In drug group, imidapril (3 mg·kg^-1·d^-1) was given to the rats once daily for 1 week by intragastric gavage after given 6% ammonium chloride. On the 7th day, the rats were anesthetized with 2% so-dium pentobarbital. Abdominal aorta blood, venous blood and lung tissue were collected. The blood gas indexes and serum TNF-α, IL-6 and MDA concentrations were determined. The lung tissues were fixed and sliced, and the expression of AngⅡ and CD54 proteins was detected by immunohistochemistry. RESULTS: The PaCO₂ increased in lung injury model group compared with control group and drug group (P < 0.05).The expression of AngⅡ and CD54, and the concentrations of TNF-α, IL-6 and MDA also increased significantly (P < 0.01) in model group. Pulmonary edema, inflammation, alveolus congestion, hemorrhage and hyperplasia in model group were obvious compared with control group and drug group. CONCLUSION: Imidapril improves blood gas indexes, and reduces lipid peroxidation and inflammatory responses in the rats with lung injury induced by ammonium chloride.     

Progress in mitochondrial fusion,fission and inflammatory response

The dynamism and health of the mitochondrial network are regulated by fission and fusion proteins, which help to maintain organelle vitality and the physiological state of the cell. Recently, accumulated evidence has demonstrated that the changes of mitochondrial dynamics have a great effect on inflammation in a variety of diseases. To the contrary, inflammatory mediators regulate mitochondrial dynamics at the same time. The aim of this reviews is to summarize the relationship between them and to provide new clinical reference for preventing and curing diseases.     

Effects of Shengmai San on oxidative damage in mentally stressed mice

AIM: To investigate the preventive effects of Shengmai San (SMS) on oxidative damage in mentally stressed mice.METHODS: An oxidative stress mouse model was established by moustache-removed. Protein carbonyl and thiobarbituric acid reactive substance (TBARS) formation were determined as the oxidative stress markers.RESULTS: (1)Moustache-cut was founded to significantly enhance the behavioral movements of mice, especially large movements (movement 2 and rearing). SMS pre-administration inhibited the accelerated movements. (2) Protein carbonyl was increased in brain, heart, liver and kidney. TBARS in liver and heart increased in the moustache-cut mice, but SMS pretreatment inhibited the increased protein carbonyl and TBARS.CONCLUSION: SMS has the preventive effects on oxidative damage induced by emotional stress.     

Effects of FGF-21 and Nrf2 on BLM-induced pulmonary fibrosis in mice

AIM:To investigate the effect of fibroblast growth factor-21 (FGF-21) on bleomycin (BLM)-induced inflammatory response and oxidative stress in the lung, and to further explore the molecular mechanism of FGF-21 against pulmonary fibrosis. METHODS:The lung fibrosis model was induced by BLM intratracheal instillation. A total of 40 mice were randomly divided into control group, BLM group, FGF-21 (1, 2 and 5 mg/kg)+BLM groups. Western blot was used to detected the protein expression of collagen I, fibronectin and nuclear factor E2-related factor 2 (Nrf2). The reactive oxygen species (ROS) production was measured by DCFH-DA staining. The levels of inflammatory cytokines were measured by ELISA. The content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and the content of hydroxyproline (HYP) were detected by commercially available assay kits. RESULTS:Treatment with FGF-21 notably attenuated BLM-induced the expression levels of inflammatory mediators tumor necrosis factor-α, interleukin-1β and interleukin-6 in the lung tissue. In addition, FGF-21 treatment remarkably reduced the generation of ROS and the content of MDA trigged by BLM, accompanied with the enhanced activity of anti-oxidative enzymes SOD and GPx (P<0.05). Furthermore, treatment with FGF-21 obviously reduced the extracellular matrix (ECM) accumulation by suppressing the expression of collagen I and fibronectin induced by BLM, accompanied with the decreases in the levels of TGF-β1 and HYP. Silencing of Nrf2 expression abolished the protective effect of FGF-21. CONCLUSION:FGF-21 relieves BLM-induced pulmonary fibrosis by reducing the inflammatory response, mitigating oxidative damage and decreasing the ECM deposition via Nrf2 activation, thus providing the basis for the therapeutic effect of FGF-21 on the lung fibrosis.     

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.     

Sevoflurane preconditioning inhibits brain injury in hypoxic mice

AIM: To observe the effects of sevoflurane preconditioning on brain injury in hypoxic mice and its possible mechanism. METHODS: Male C57BL/6J mice were randomly divided into control (C) group, hypoxia (H) group, 2% sevoflurane preconditioning for 30 min + hypoxia (S1+H) group, 2% sevoflurane preconditioning for 60 min+hypoxia (S2+H) group and 4% sevoflurane preconditioning for 30 min + hypoxia (S3+H) group. The hypoxia model was established by continuous inhalation of (6.5±0.1)% O₂ for 24 h. The sevoflurane preconditioning treatments, S1, S2 and S3, were conducted by inhalation of 2% sevoflurane for 30 min, 2% sevoflurane for 60 min and 4% sevoflurane for 30 min, respectively, with the carrier of (21.0±0.5)% O₂, followed by washout for 15 min and then hypoxia treatment. The histological changes of the hippocampal CA1 area were observed under light microscope and transmission electron microscope (TEM), and serum lactate dehydrogenase (LDH) activity was measured by colorimetric method. Furthermore, the protein levels of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in brain tissue homogenate were examined by ELISA, and the content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured by microplate reader. RESULTS: After hypoxia for 24 h, cell edema or pyknosis in the hippocampal CA1 area was observed in H group. Sevoflurane preconditioning reduced hypoxic injury, and the cell ultrastructure under TEM was significantly improved in S2+H group. Compared with C group, the serum LDH activity and the levels of EPO, VEGF and MDA in brain tissues were significantly increased in H group, while the activity of SOD and GPx decreased. After sevoflurane pretreatment, the serum LDH activity and the levels of EPO and VEGF in brain tissues were lower than those in H group, and the most significant difference was observed in S2+H group. Moreover, the MDA content and SOD activity decreased, and the GPx activity increased in the sevoflurane preconditioning groups. CONCLUSION: Sevoflurane preconditioning attenuates brain injury in hypoxic mice by regulating antihypoxic protein synthesis and reducing oxidative stress.     

Effects of N-acetylcysteine combined with azithromycin on oxidative stress in rats with chronic obstructive pulmonary disease

AIM: To investigate the effects of N-acetylcysteine (NAC) combined with azithromycin (AZI) on oxidative stress in the rats with chronic obstructive pulmonary disease (COPD). METHODS: Male Wistar rats (n=60) were randomly divided into control group, model group, AZI intervention group,NAC intervention group and AZI+NAC group. The COPD model was established by passive smoking and intratracheal instillation of lipopolysaccharide. Each day 30 min prior to smoking, intragastric administration with AZI, NAC or combination of the 2 drugs was given for AZI, NAC, and AZI+NAC groups, respectively. On the 31st day, all rats were killed following lung function test. Cell counts of bronchoalveolar lavage fluid (BALF) were performed, and the contents of interleukin-8 (IL-8), interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-α) in BALF were measured by ELISA. The histopathology of the lung tissues was observed under light microscope, and the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in the lung homogenate were measured. RESULTS: Compared with control group, the other 4 groups showed decreased pulmonary function, and inflammatory cell infiltration and alveolar destruction in histopathology. Compared with control group, the other groups showed higher white blood cells, monocyte-macrophages, neutrophils and lymphocytes in the BALF (P<0.05). Compared with model group, AZI group and NAC group, lower white blood cells, neutrophils and lymphocytes in the BALF were observed in AZI+NAC group (P<0.05). Compared with model group, IL-8, IL-17, TNF-α and MDA in AZI group, NAC group and AZI+NAC group significantly decreased (P<0.05), while SOD and GSH-Px significantly increased (P<0.05). Compared with AZI or NAC group, IL-8, IL-17, TNF-α and MDA in AZI+NAC group significantly decreased (P<0.05), while SOD and GSH-Px increased significantly (P<0.05). CONCLUSION: Both NAC and AZI attenuate the lung inflammation and oxidative damage in COPD model rats. Combined medication exerts preferable anti-oxidation effects, which might be more suitable for the treatment of COPD.     

Effects of cyclosporin on oxidative stress and mitochondrial energy metabolism in rat hippocampus after status epilepticus

AIM：To investigate the effects of cyclosporin on oxidative stress and mitochondrial energy metabolism in the rat hippocampus after status epilepticus. METHODS：Status epilepticus was induced by pilocarpine. The changes of malondialdehyde and superoxide dismutase in the rat hippocampus with or without cyclosporin injection were evaluated. Additionally, the mitochondrial permeability transition, the activity of mitochondrial respiratory chain complex I/III and ATP content in the rat hippocampus were detected. RESULTS：Cyclosporin significantly inhibited mitochondrial permeability transition in the rat hippocampus after status epilepticus. Decreased malondialdehyde and increased superoxide dismutase levels were detected in cyclosporin treatment group compared with status epilepticus group (P<0.05). More-over, the activity of mitochondria respiratory chain complex I, not III, in the mitochondrial fraction increased after cyclo-sporin treatment (P<0.05). In addition, cyclosporin significantly prevented the decrease of ATP content in rat hippocampus after status epilepticus (P<0.05). CONCLUSION：Cyclosporin suppresses oxidative stress in the rat hippocampus after status epilepticus. Cyclosporin alleviates the impairment of mitochondrial energy metabolism in rat hippocampus after status epilepticus.