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目的:观察膈下逐瘀汤对大鼠纤维化肝脏组织氧化应激及谷胱甘肽(glutathione,GSH)抗氧化系统的影响。方法:60只大鼠随机分为空白组、正常组、模型组,膈下逐瘀汤组。以猪血清腹腔注射(0.5 m L/只,2次/周)制备免疫性大鼠肝纤维化模型,同时各组大鼠分别给予生理盐水或膈下逐瘀汤(生药7.37 g·kg~(-1)·d~(-1))灌胃共12周。采用分光光度法检测肝组织丙二醛(MDA)和GSH含量,实时荧光定量聚合酶链式反应(Real-time PCR)检测谷氨酸-半胱氨酸连接酶催化亚基(glutamate-cysteine ligase catalytic subunit,GCLc)mRNA表达,蛋白免疫印迹法(Western blot)检测转录因子NF-E2相关因子2(nuclear factor erythroid 2-related factor 2,Nrf2),GCLc表达和糖原合酶激酶-3β(glycogen synthasc kinase-3β,GSK-3β)磷酸化。结果:与模型组比较,膈下逐瘀汤显著抑制了纤维化肝脏组织MDA含量(P<0.05),增加了GSH含量(P<0.05),上调了GCLc和Nrf2表达(P<0.05),提高了GSK-3β磷酸化水平(P<0.05)。结论:膈下逐瘀汤通过活化Nrf2信号通路增强机体肝脏GSH抗氧化系统进而缓解大鼠纤维化肝脏组织氧化应激。
Objective: To observe the effect of Gexia Zhuyu Decoction on the oxidative stress and the antioxidant system of glutathione (GSH) in hepatic fibrosis in rats. Methods: Sixty rats were randomly divided into blank group, normal group, model group and Gexia Zhuyu Decoction group. Rat model of hepatic fibrosis induced by intraperitoneal injection of porcine serum (0.5 m L / mouse, twice / week) was established. At the same time, rats in each group were given physiological saline or Gexiazhuyutang (crude drug 7.37 g · kg ~ (-1) -1) · d ~ (-1)) for 12 weeks. The contents of malondialdehyde (MDA) and GSH in liver tissues were detected by spectrophotometry, and the expression of glutamate-cysteine ligase was detected by Real-time PCR. The expression of GCLc, Nrf2, GCLc and glycogen synthase kinase-3β were detected by Western blot. synthasc kinase-3β, GSK-3β) phosphorylation. Results: Compared with the model group, Gexiazhuyutang significantly inhibited the MDA content (P <0.05), increased the content of GSH (P <0.05) and up-regulated the expression of GCLc and Nrf2 GSK-3β phosphorylation levels (P <0.05). Conclusion: Gexia Zhuyu Decoction can enhance the oxidative stress in hepatic fibrosis of rat by enhancing Nrf2 signaling pathway.