肝灵对胆汁淤积性肝硬化大鼠肝组织MMP-13、TIMP-1和NF-κBp65表达的影响  

Effect of Ganling on MMP-13,TIMP-1 and NF-κBp65 expression in hepatic cirrhosis of cholestasis

作　　者：朱虹[1] 吴樱樱[1] 徐明[1] 胡秀萍[1] 吴强[2] 杨雁[1] 陈敏珠[1] 

机构地区：[1]安徽医科大学药理教研室,合肥230032 [2]安徽医科大学病理学教研室,合肥230032

出　　处：《安徽医科大学学报》2005年第6期515-518,共4页Acta Universitatis Medicinalis Anhui

摘　　要：目的探讨肝灵抗大鼠胆汁淤积性肝硬化的作用机制。方法利用胆总管结扎术(BDL)制备大鼠肝脏胆汁淤积性肝硬化模型,于造模第4周起ig给予肝灵8g/(kg·d),连续2周,第5周末股动脉放血处死大鼠,取左叶肝组织石蜡包埋,制作组织芯片。免疫组化SP法检测肝组织中MMP13、TIMP1和NFκBp65蛋白的表达,并用显微图像分析系统对免疫组化结果进行定量分析。结果与假手术对照组相比,胆汁淤积性肝硬化模型组的大鼠肝组织MMP13、TIMP1和NFκBp65蛋白的表达均明显增强(P<0.01),肝灵可使BDL诱导的胆汁淤积性肝硬化大鼠升高的肝组织TIMP1、NFκBp65蛋白表达明显降低(P<0.01);同时促进升高的肝组织MMP13表达增强(P<0.01),上调其低下的MMP13/TIMP1的比值。结论肝灵通过调节BDL诱导的肝硬化大鼠肝组织MMP13和TIMP1的异常表达而提高MMP13/TIMP1的比值,加速ECM分解,发挥抗肝纤维化和使肝纤维化逆转的作用;肝灵还可通过抑制肝硬化组织NFκBp65蛋白的表达发挥其抗肝纤维化作用。Objective To explore the mechanisms of Ganling in hepatic cirrhosis of cholestasis. Methods Rat model of hepatic cirrhosis of cholestasis was induced through bile duct ligation. Ganling [8 g/（kg · d）] was intragastricaly administrated in the 4th week. The rats were killed at the end of the 5th week, and then the left liver tissues were used to make tissue microarrays （TMA）. Immunohistochemical S-P method was used to detect the protein expression of MMP-13,TIMP-1 and NF-κBp65 protein. The expression of MMP-13,TIMP-1 and NF-κBp65 protein was quantified using Image-Pro Plus 5.0. 1 analysis system. Results The expression of MMP-13,TIMP-1 and NF-κBp65 protein in cirrhosis model liver tissue was stronger than that in sham（P 〈 0. 01 ）. Ganling markedly reduced TIMP-1 and NF-κBp65 expression in hepatic cirrhosis of cholestasis（P 〈0.01 ）, and enhanced MMP-13 expression（P 〈 0. 01 ）. Conclusion Through elevating MMP-13 expression and reducing TIMP-1 expression in hepatic cirrhosis of cholestasis,Ganling increase MMP-13/TIMP-1 ratio, and accelerates degradation of extracellular matrix. Furthermore, Ganling can reduce NF-κBp65 protein expression. All of those may be related to its anti-fibrosis mechanisms.

关 键 词：肝硬化 胆汁性 药物疗法 肝硬化 实验性 

分 类 号：R977.1[医药卫生—药品] R575.2[医药卫生—药学]