抑毒调肝合剂抗大鼠肝纤维化的作用及机制研究
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篇名: 抑毒调肝合剂抗大鼠肝纤维化的作用及机制研究
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摘要: 目的:研究抑毒调肝合剂抗大鼠肝纤维化的作用及机制。方法:将60只SD大鼠随机分为正常组、模型组、秋水仙碱组(阳性对照,0.2 mg/kg)和抑毒调肝合剂低、中、高剂量组(2.7、5.4、10.8 mL/kg)。除正常组外,其余各组大鼠均复制肝纤维化模型,并于造模同时ig相应药物,每天1次,连续8周。检测大鼠血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(CⅣ)、基质金属蛋白酶组织抑制因子1(TIMP-1)、基质金属蛋白酶1(MMP-1)、MMP-2、MMP-13、转化生长因子β1(TGF-β1)、肿瘤坏死因子α(TNF-α)水平和肝组织中羟脯氨酸(Hyp)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)、丙二醛(MDA)、TGF-β1、TNF-α水平。结果:与正常组比较,模型组大鼠血清中ALT、AST、HA、PCⅢ、CⅣ、TIMP-1、MMP-2、TGF-β1、TNF-α水平显著升高,MMP-1、MMP-13水平显著降低(P<0.05); 肝组织中Hyp、TGF-β1、TNF-α、MDA水平显著升高,SOD、GSH-Px、CAT水平显著降低(P<0.05)。与模型组比较,抑毒调肝合剂中、高剂量组和秋水仙碱组大鼠血清中ALT、AST、HA、PCⅢ、CⅣ、TIMP-1、TNF-α水平以及肝组织中Hyp、TGF-β1、TNF-α、MDA水平均显著降低(P<0.05);抑毒调肝合剂高剂量组和秋水仙碱组大鼠血清中MMP-1、MMP-13水平以及肝组织中CAT水平均显著升高(P<0.05),且血清中MMP-2、TGF-β1水平显著降低(P<0.05);抑毒调肝合剂低剂量组大鼠上述指标差异均无统计学意义(P>0.05)。结论:抑毒调肝合剂抗大鼠肝纤维化的作用机制可能与调节TIMP/MMP平衡、抗氧化应激、降低TGF-β1水平和减少细胞外基质沉积有关。
ABSTRACT: OBJECTIVE: To study the anti-hepatic fibrosis effects of Yidu tiaogan mixture on rats and its mechanism. METHODS: 60 SD rats were randomly divided into normal group, model group, colchicine group (positive control, 0.2 mg/kg) and Yidu tiaogan mixture low-dose, medium-dose and high-dose groups (2.7, 5.4, 10.8 mL/kg). Except for normal group, liver fibrosis model was induced in other groups, and they were given relevant medicine intragastrically during modeling, once a day, for 8 weeks. Serum levels of ALT, AST, HA, PCⅢ, CⅣ, TIMP-1, MMP-1, MMP-2, MMP-13, TGF-β1 and TNF-α and the levels of Hyp, SOD, GSH-Px, CAT, MDA, TGF-β1 and TNF-α in liver tissue were detected in rats. RESULTS: Compared with normal group, the serum levels of ALT, AST, HA, PCⅢ, CⅣ, TIMP-1, MMP-2, TGF-β1 and TNF-α were increased significantly in model group, while the serum levels of MMP-1 and MMP-13 were decreased significantly (P<0.05); the levels of Hyp, TGF-β1, TNF-α and MDA in liver tissue were increased significantly, while the levels of SOD, GSH-Px and CAT were decreased significantly (P<0.05). Compared with model group, the serum levels of ALT, AST, HA, PCⅢ, CⅣ, TIMP-1 and TNF-α as well as the levels of Hyp, TGF-β1, TNF-α and MDA in liver tissue were all decreased significantly of rats in Yidu tiaogan mixture medium-dose,high-dose and colchicine groups (P<0.05); the serum levels of MMP-1 and MMP-13 as well as the level of CAT in liver tissue were increased significantly in Yidu tiaogan mixture high-dose group and colchicine group (P<0.05), while the serum levels of MMP-2 and TGF-β1 were decreased significantly (P<0.05). There was no statistical significance in above indexes in Yidu tiaogan mixture low-dose group (P>0.05). CONCLUSIONS: Yidu tiaogan mixture exerts protective effects on liver fibrosis of rat through regulating TIMP/MMP balance, suppressing oxidative stress, decreasing the level of TGF-β1 and reducing deposition of extracellular matrix in liver.
期刊: 2017年第28卷第4期
作者: 罗宏丽,肖顺林,余欣
AUTHORS: LUO Hongli,XIAO Shunlin,YU Xin
关键字: 抑毒调肝合剂;肝纤维化;大鼠
KEYWORDS: Yidu tiaogan mixture; Liver fibrosis; Rat
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