摘要
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 : The aim of this study was to investigate the effects of Gexia Zhuyutang on oxidative stress and glutathione (GSH) antioxidant system in liver tissues of rats with hepatic fibrosis. Method: A total of 60 rats were randomly divided into blank group, normal group, model group, and Gexia Zhuyutang group. The hepatic fibrosis model of rats was established by intraperitoneal injection of porcine serum twice weekly (0.5 mL/rat) , and Gexia Zhuyutang (crude drug 7.37 g·kg^-1·d^-1) or normal saline was simultaneously administered daily by gavage for 12 weeks. Malondiadehyde (MDA) and glutathione (GSH) levels in liver tissues were determined by colorimetric method. Real-time PCR was used to analyze glutamate-cysteine ligase catalytic subunit (GCLc) mRNA expression, and Western blot was used to analyze the glycogen synthasc kinase-3β (GSK-3β) phosphorylation and GCLc protein expression in the liver. Result: As compared with the model group, Gexia Zhuyutang significantly inhibited MDA content and increased GSH content in fibrotic liver tissues, up-regulated GCLc expression, nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression, and increased GSK-3β) phosphorylation level. Conclusion: Gexia Zhuyutang exhibited remarkable antioxidant activities in livers tissue of the porcine serum rat model, which may be correlated with the enhancement of the glutathione antioxidant system via activating Nrf2 signaling pathway.
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2017年第17期121-126,共6页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金青年基金项目(81603418)
黑龙江省自然科学基金项目(H2016062
D200820)
黑龙江省普通本科高等学校青年创新人才培养计划项目(UNPYSCT-2016075)