Objective To investigate the effects of glutathione (GSH) on survival of the random skin flap in rats and the probable mechanism that contribute to this effect. Methods Twenty SD rats with 200-250 g in weight, were randomly divided into the experimental group and control group(n=10). Random flap of 8 cm×2 cm in size was made on the back of each rat with the pedicel on the angular of the scapular. GSH(250 mg/kg) and NS of the same dose were injected into the abdominal cavity of rats in the experimental groupand the control group immediately after the operative, 1st and 2nd days respectively. The rats were killed on the 7th day after the operation. The tissue pathology, the survival rate of the flap, the superoxide dismutase(SOD) activity and malonyldialdehyde (MDA) level were compared between two groups. Results The mean survival rate of the flap on the 7th day in the experimental group（56.77%±10.67%） was higher than that in the control group(40.16%±7.12%)(Plt;0.05).SOD activity in experimental group （306.06±84.87 U/mgprot）was higher than that in the control group （224.79±27.12 U/mgprot）, while MDA level （3.835±0.457 nmol/mgprot）was lower than that in the control group (6.127±0.837 nmol/mgprot)(Plt;0.05). Histological observation showed that the neutrophil infiltration was less in experimental group than that in the control group; that the experimental group was surperior to the control group in angiogenesis, fibroblasts, fair cells and cuaneous gland. Conclusion The intraperitoneal use of GSH may promote the survival rate of the random flaps and the possible mechanism for improvement may lies in that the GSH can reduce the level of oxygen free radical and lipidperoxidation,and lessen neutrophil infiltration.
Objective To investigate the protective effect of the antioxidant glutathione (GSH) on the steroid-induced imbalance between osteogenesis and adipogenesis in human bone marrow mesenchymal stem cells (BMSCs). Methods The BMSCs were isolated from the proximal femur bone marrow from 3 patients of femoral neck fracture and were separated, cultured, and purificated by density gradient centrifugation and adherent wall methodin vitro. The third generation BMSCs were divided into 5 groups: group A, BMSCs (1×105 cells/mL); group B, BMSCs (1×105 cells/mL)+10 μmol/L dexamethasone; group C, BMSCs (1×105 cells/mL)+10 μmol/L dexamethasone+5 μmol/L GSH; group D, BMSCs (1×105 cells/mL)+10 μmol/L dexamethasone+10 μmol/L GSH; group E, BMSCs (1×105 cells/mL)+10 μmol/L dexamethasone+50 μmol/L GSH. After cultured for 7 days, the reactive oxygen species expression was detected by flow cytometry; the superoxide dismutase (SOD) and Catalase mRNA expressions were determined by RT-PCR; the peroxisome proliferator-activated receptors γ (PPAR-γ), CCAAT/enhancer-binding family of proteins (C/EBP), Runx2, and alkaline phosphatase (ALP) mRNA expressions were evaluated by real-time fluorescence quantitative PCR. After cultured for 21 days, Oil red O staining was used to observe the adipogenesis differentiation of cells, and the expressions of related proteins were detected by Western blot. Results The reactive oxygen species expression in group B was obviously higher than in the other groups, in group C than in groups A, D, and E, and in groups D, E than in group A, all showing significant differences between groups (P<0.05); but there was no significant difference between groups D and E (P>0.05). The oil red O staining positive cells in group B were obviously more than the other groups, and groups C, D, E, and A decreased sequentially, the absorbance (A) values had significant differences between groups (P<0.05). RT-PCR detection showed that the relative expressions of SOD and Catalase mRNA in group B were significantly lower than those in the other groups, while in group C than in groups A, D, and E (P<0.05), but there was no significant difference among groups A, D, and E (P>0.05). Real-time fluorescence quantitative PCR detection showed that the relative expressions of PPAR-γ and C/EBP mRNA in group B were significantly higher than those in the other groups, while in group C than in groups A, D, and E, and in groups D, E than in group A (P<0.05); but there was no significant difference between groups D and E (P>0.05). The relative expressions of Runx2 and ALP mRNA in group B were significantly lower than those in the other groups, while in group C than in groups A, D, and E, and in groups D, E than in group A (P<0.05); but there was no significant difference between groups D and E (P>0.05). Western blot detection showed that the relative expression of PPAR-γ and C/EBP protein in group B was significantly higher than those in the other groups, and groups C, D, E, and A decreased sequentially, all showing significant differences between groups (P<0.05). The relative expression of Runx2 and ALP protein in group B was significantly lower than those in the other groups, and groups C, D, E, and A increased sequentially, all showing significant differences between groups (P<0.05). Conclusions GSH can inhibit the adipogenesis differentiation and enhance the osteogenic differentiation of human BMSCs by reducing the intracellular reactive oxygen species level; and in a certain range, the higher the concentration of GSH, the more obvious the effect is.
ObjectiveTo explore the antioxidant effects of reduced glutathione on rat pulmonary fibrosis compared with traditional corticosteroid. MethodsOne-hundred and eight healthy SD rats were randomly divided into 6 groups,ie. a control group,a model group,a dexamethasone group,a low-dose glutathione group,a middle-dose glutathione group,and a high-dose glutathione group,with 18 rats in each group. The pulmonary fibrosis model was established by intratrachially instillation of bleomycin in all rats except the control group. The severity of lung fibrosis was evaluated by HE staining and Masson staining of collagen,and measurement of glutathione,hydroxyproline,superoxide dismutase (SOD),glutathion peroxidase (GSH-Px)in lung tissue homogenate by photocolorimetric method. ResultsOn 7th day and 14th day after bleomycin instillation, the severity of alveolitis in the model group,the dexamethasone group,and three glutathione intervention groups was significantly reduced compared with the control group (P<0.05). On 28 day, the severity of lung fibrosis was significantly reduced in the dexamethasone group and three glutathione intervention groups compared with the model group (P<0.05). On 7th day,lung glutathione content was significantly lower in the model group compared with the control group (P<0.05), significantly higher in the dexamethasone group and three glutathione intervention groups compared with the model group (P<0.05), significantly lower in the dexamethasone group and the low-dose glutathione group compared with the control group (P<0.05), and significantly higher in the high-dose glutathione group compared with the dexamethasone group (P<0.05). On 7th,14th,and 28th day,the hydroxyproline content in the dexamethasone group and three glutathione intervention groups decreased significantly compared with the model group (P<0.05). On 14th day,the hydroxyproline content in the middle-dose and high-dose glutathione groups was significantly lower than that in the dexamethasone group (P<0.05). SOD and GSH-Px were significantly reduced in the model group compared with the control group on all time points (P<0.05),but significantly increased after intervention by different doses of glutathione (P<0.05). ConclusionReduced glutathione can significantly reduce the degree of pulmonary fibrosis in rats,but has no obvious advantage over dexamethasone.
ObjectiveTo systematically review the association between glutathione S-transferase pi (GSTP1) Ile105Val (A/G) and the risk of cutaneous melanoma. MethodWe searched PubMed, EMbase, CNKI and WanFang Data to identify case-control studies which investigated the association between GSPT1 Ile105Val (A/G) polymorphism and the risk of cutaneous melanoma from their inception to June 31th 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed by using RevMan 5.3 software. ResultsA total of 4 case-control studies involving 978 cutaneous melanoma cases and 796 controls were included. The results showed that: the GSPT1 Ile105Val (A/G) polymorphism was significantly associated with the risk of cutaneous melanoma in the dominant model (GG+GA vs. AA: OR=1.22, 95%CI 1.01 to 1.48, P=0.04), but no significant association was found in the recessive model, heterozygote model, and homozygote model (GG vs. CA+AA: OR=1.18, 95%CI 0.86 to 1.60, P=0.30; GA vs. AA: OR=1.20, 95%CI 0.98 to 1.47, P=0.08; GG vs. AA: OR=1.28, 95%CI 0.92 to 1.77, P=0.14). ConclusionCurrent evidence shows, The GSTP1 Ile105Val (A/G) polymorphism is associated with the risk of cutaneous melanoma. Due to limited quantity and quality of the included studies, more high-quality large-scale studies are needed to verify the above conclusion.
ObjectiveTo establish a cell inflammation model induced by tumor necrosis factor-α (TNF-α) in human bronchus epithelial cells, and investigate the effects of glutathione S-transferase mu 5 (GSTM5) on the inflammation and oxidative stress. Methods16HBE cells were treated with TNF-α (10 ng/mL, 24 h) in the absence or presence of the constructed GSTM5 eukaryotic expression vector (1 μg/mL). The concentration of malondialdehyde (MDA) and total antioxidation capacity (T-AOC) were detected by colorimetric method. The survival rate of cells was assessed by the methyl thiazolyl tetrazolium (MTT) assay. The transcription level of NADPH oxidase-1 (NOX1), NOX2, NOX3, NOX4, NOX5, dual oxidase-1 (DUOX1) and DUOX2 were evaluated by RT-PCR. Western blot was performed to investigate the protein levels of NOX1 and NOX2. ResultsTNF-α simulation significantly increased the level of MDA in cells, and decreased the level of T-AOC and survival rate of 16HBE. When transfected with the GSTM5 eukaryotic expression vector, the concentration of MDA significantly decreased (P < 0.05), and the activation of T-AOC increased dramatically (P < 0.05). Consequently, the survival rate of 16HBE in the GSTM5 group improved (P < 0.05). The 16HBE cells transfected with the constructed GSTM5 eukaryotic expression vector had a lower transcription and protein levels of NOX1 and NOX2 (all P < 0.01). There were no significant changes in the mRNA expressions of NOX3, NOX4, NOX5, DUOX1 or DUOX2. ConclusionGSTM5 may down-regulate the transcription level of NOX1 and NOX2 to reduce the inflammation and oxidative stress induced by TNF-α.
目的:研究大豆异黄酮对D半乳糖致衰老大鼠抗氧化能力的影响。方法:用D半乳糖注射Wistar雄性大鼠5个月,建立衰老模型。对致衰老模型组、大豆异黄酮组肝脏、心脏和前列腺丙二醛(MDA)含量、超氧化物歧化酶(SOD)、谷胱甘肽过氧化酶(GSHPx)活性进行测定及比较。结果:低、中、高不同剂量大豆异黄酮灌喂组与模型组大鼠相比,各脏器MDA含量(μmol/L)(心脏:695±093,562±112,435±112比802±111;肝脏:815±085,647±120,515±112比935±135;前列腺:715±092,558±115,423±125比833±124)均有降低,差异有统计学意义(Plt;005),而SOD酶活性(nmol/L)(心脏:4732±308,5518±428,6120±368比3225±370;肝脏:18121±506,19015±706,19720±570比17213±512;前列腺:4156±301,4607±421,5015±335比3374±305)和GSHPx酶活性(nmol/L)(心脏:905±096,1111±245,1313±146比713±151;肝脏:902±105,1150±223,1362±192比698±160;前列腺:435±085,613±102,747±155比312±106)有升高,差异同样具有统计学意义(Plt;005);大豆异黄酮摄入量越高,MDA含量越低,而SOD、GSHPx酶活性越高。结论:摄入适量大豆异黄酮可有效增强大鼠机体抗氧化能力,从而延缓D半乳糖诱发的大鼠衰老。
Objective To study the protective effect of glutamine on the intestinal mucosal antioxidation in endotoxemic rats. Methods Twenty-eight male Wistar rats were randomly divided into three groups, group A:parenteral nutrition supplemented with glutamine, group B:TPN without glutamine,and group C:normal control. Endotoxemia was induced by continous intravenous infusion of lipopolysaccharide(LPS) at a dose of 2 mg/kg per day throughout the 5-day study period. The mucosal protein、DNA、ATP、SOD、MDA、GSH、sIgA were determined. Results The mucosal protein、DNA、ATP、SOD、GSH and sIgA content in endotoxic rats were markedly decreased, MDA was increased as compared with normal control(P＜0.05). The former indices in group A were improved and MDA content was decreased as compared with group B(P＜0.05). Conclusion Glutamine can improve gut energy metabolism, decrease the extent of mucosal injury of free radicals, and give an protective effect on the mucosal probably by increasing GSH.
目的 探讨异氟醚通过抑制细胞间黏附分子（ICAM-1）表达参与减轻肝脏缺血-再灌注（IR）损伤的可能调节机制。 方法 32只雌性SD大鼠分为4组。A组大鼠行腹腔注射1%戊巴比妥钠40 mg/kg麻醉，进行手术但不阻断入肝血流；B组1%戊巴比妥钠麻醉后行部分肝脏IR；C组大鼠仅接受1.0 MAC异氟醚吸入麻醉，不阻断血流；D组采用1.0 MAC异氟醚麻醉，建立肝脏IR模型。肝脏缺血60 min，再灌注3 h后取肝组织和血液标本，检测血清丙氨酸转氨酶（ALT）和天冬门氨酸转氨酶（AST）、肝组织ICAM-1和肝组织还原型谷胱甘肽（GSH）、脂质过氧化物丙二醛（MDA）和超氧化物歧化酶（SOD）含量。 结果 与戊巴比妥钠麻醉比较，采用异氟醚处理后明显降低血清ALT和AST的水平，再灌注肝组织内GSH、SOD含量明显高于而MDA含量降低，同时抑制肝组织ICAM-1的表达。 结论 异氟醚麻醉能够有效减轻肝脏IR损伤，抑制氧自由基的生成和释放，具体机制可能与抑制ICAM-1表达致使细胞内GSH含量增加密切相关。
Objective To investigate the expression of presenilin-2(PS2) and glutathione S transferase π(GSTπ) and their role in the prognosis and therapy of infiltrating ductal breast carcinoma. Methods The expression of PS2 and GSTπ in tumor tissues from 210 patients with infiltrating ductal breast carcinoma confirmed by pathologic examination and treated with modified radical mastectomy was examined by using LSAB immunohistochemical method. Results The expression rate of PS2 was 49.5%(104/210) and the expression rate of GSTπ was 48.1%(101/210). The grade of the postoperative 5-year survival rate and 10-year survival rate in four groups of 210 patients, from high to low, was the group 1 (PS2 positive expression/GSTπ negative expression), the group 2 (PS2 positive expression/GSTπ positive expression), the group 3 (PS2 negative expression/GSTπ negative expression) and the group 4 (PS2 negative expression/GSTπ positive expression). Conclusion The prognosis of the group 1 is the best, the group 2 better, the group 3 good and the group 4 the worst. The results suggest that reasonable use of endocrinotherapy and chemotherapy in infiltrating ductal breast carcinoma is necessary.
Objective To investigate the relationship between the expressions of P-gp, GST-π and C-erbB-2 and clinicopathologic characteristics as well as prognosis in breast cancer. Methods The expressions of P-gp， GST-π and C-erbB-2 were detected by immunohistochemistry in 48 cases of breast cancer, and histopathologic characteristics as well as 5-year survival rate of these cases were analyzed. Results There was no significant difference in the expressions of P-gp and GST-π with age, histologic grade, number of lymph node metastasis and TNM stage of breast cancer ( P ＞ 0.05). There was significant difference in expression of C-erbB-2 with histologic grade, number of lymph node metastasis and TNM stage of breast cancer （ P ＜ 0.05）. Positive rate of P-gp expression in breast cancer with positive C-erbB-2 expression was remarkably higher than that in breast cancer with negative C-erbB-2 expression ( P ＜ 0.05) . Positive rate of GST-π and C-erbB-2 expression in survivals within 5 years was remarkably lower than that in deaths within 5 years ( P ＜ 0.01). Conclusion P-gp participates primary drug-resistance mechanism of breast cancer. The possibility of primary drug-resistance is higher in breast cancer with positive C-erbB-2 expression. The expression of C-erbB-2 helps to evaluate prognosis and the result of treatment in breast cancer.