【作者】 乔胃娟；

【导师】 杨宇；

【作者基本信息】 成都中医药大学 ， 中医临床基础， 2010， 博士

【摘要】 目的：观察加减三甲散及其拆方滋阴养血药物对实验性肝纤维化时肝组织TGF-β/Smads转导通路的影响,探讨其抗肝纤维化的作用机理。方法：通过四氯化碳诱导造成大鼠肝纤维化模型,应用TUNEL法、放射免疫法、免疫组化法以及原位杂交法探索加减三甲散及其拆方滋阴养血药物抗肝纤维化的作用机理。结果：1、加减三甲散组能显著改善大鼠的精神状态、饮食、皮毛色泽、体重以及病理切片等情况,降低大鼠血清PIIINP与HA的含量与肝组织凋亡细胞数(P<0.01),抑制肝纤维化大鼠TGF-β1以及Smad2/3的表达(P<0.01),能抑制PAI-1(P<0.05)以及a2(Ⅰ)前胶原mRNA的表达(P<0.01)。2、加减三甲散拆方滋阴组能改善大鼠的精神状态、饮食、皮毛色泽、体重以及病理切片等情况,能降低肝组织凋亡细胞数(P<0.01),抑制Smad2/3的表达(P<0.01),同时可以通过协同活血化瘀药物以及透邪外达药物一起降低PⅢNP及HA的含量,抑制TGF-β1、PAI-1以及a2(Ⅰ)前胶原mRNA的表达。结论：1、加减三甲散的治疗作用：加减三甲散可改善肝纤维化大鼠的一般情况,可显著改善肝纤维化大鼠肝组织肝纤维化程度及病理状态,对肝脏有一定的保护及治疗作用,其治疗效果优于拆方滋阴养血药物。2、加减三甲散抗肝纤维化的作用机理：加减三甲散主要是通过抑制肝细胞的凋亡,抑制肝纤维化大鼠肝组织TGF-β1、Smad2/3的表达,同时,通过抑制肝纤维化大鼠肝组织TGF-β1的表达,从而抑制PAI-1以及a2(Ⅰ)前胶原mRNA的表达等环节发挥作用。3、加减三甲散拆方滋阴养血药物的治疗作用：加减三甲散拆方滋阴养血药物可改善肝纤维化大鼠的一般情况,可轻微改善肝纤维化大鼠肝组织肝纤维化程度以及病理状态,对肝脏有一定的保护及治疗作用。4、加减三甲散拆方滋阴养血药物抗肝纤维化的作用机理：加减三甲散拆方滋阴养血药物主要是通过抑制肝细胞的凋亡以及抑制Smad2/3的表达从而发挥抗肝纤维化的作用；同时,可以通过协同活血化瘀药物以及透邪外达药物一起抑制肝纤维化大鼠TGF-β1、PAI-1以及a2(Ⅰ)前胶原mRNA表达,从而发挥抗肝纤维化的作用。更多还原

【Abstract】 Objective:To clarify the mechanism of Modified San Jia Powder and its Sub-Formulas(Yin-blood-enriching) on hepatic fibrosis by observing the Effects of them on TGF-β/Smads signaling pathway of rats with hepatic fibrosis.Methods:copying the hepatic fibrosis model in rats by CCl4, and using TUNEL、RIA、SP and in situ hybridization technique to inquire the mechanism of Modified San Jia Powder and Its Sub-Formulas on Hepatic Cell Apoptosis of Rats with Hepatic Fibrosis.Results:1. Modified San Jia Powder is helpful to improve the general health situation of rats in terms of activity, appetite, skin color, luster, weight and Pathomorphology. It can decrease the level of PⅢNP,HA and Apoptosis(P< 0.01), can inhibit the expression of TGF-β1 (P<0.01), Smad2/3 (P<0.01), PAI-1 (P< 0.05) and a2 (I) precollagen mRNA (P<0.01)。2. The group of Yin-blood-enriching is helpful to improve the general health situation of rats in terms of activity, appetite, skin color, luster, weight and Pathomorphology. It can decrease the level of Apoptosis(P<0.01), can inhibit the expression of Smad2/3 (P<0.01), and can decrease the level of PIIINP,HA, inhibit the expression of TGF-β1, PAI-1 and a2 (I) precollagen mRNA with herbs of activating blood and dissolving stasis and of expelling Evil.Conclusions:1. The effects of Modified San Jia Powder:Modified San Jia Powde can improve the rats`general health situation and reduce the fibrotic degree of rats hepatic tissue to protect and treat hepatic fibrosis. The result of Modified San Jia Powder is better than herbs of Yin-blood-enriching. 2. The mechanism of Modified San Jia Powder:Modified San Jia Powder can treat hepatic fibrosis by decreasing the level of PⅢNP,HA and Apoptosis, inhibiting the expression of TGF-β1, Smad2/3, PAI-1 and a2 (Ⅰ) precollagen mRNA.3. The effects of Yin-blood-enriching:The method of Yin-blood-enriching can slightly improve the rats’ general health situation and Pathomorphology to treat hepatic fibrosis.4. The mechanism of Yin-blood-enriching:The method of Yin-blood-enriching can treat hepatic fibrosis by decreasing the level of Apoptosis, inhibiting the expression of Smad2/3. It also can treat hepatic fibrosis by inhibiting the expression of TGF-β1, PAI-1 and a2 (Ⅰ) precollagen mRNA with herbs of activating blood and dissolving stasis and of expelling Evil.更多还原