胆宁片对高脂模型大鼠脂肪肝及PPARα、CYP7A1表达的影响

目的:研究中成药胆宁片对实验性高脂饮食大鼠脂肪肝的治疗作用及其对过氧化物酶体增殖物激活受体α(PPARα)、胆固醇7α单加氧酶(CYPTA1)表达的影响。方法:采用高脂饲料9 wk建立大鼠脂肪肝模型,给予模型大鼠胆宁片0.317 g·kg~(-1)·d~(-1)灌服5 wk,检测肝脏三酰甘油(TG)、总胆固醇(TC)、游离脂肪酸(FFA)、过氧化氢酶(CAT),血清丙氨酸转氨酶(ALT)、TG、TC、FFA、CAT、总胆汁酸(TBA)含量,肝脂变面积,检测肝脏PPARα、PPARαmRNA和CYP7A1 mRNA的表达。结果:高脂饮食可引起大鼠肝脏明显脂肪性变,肝脏TG、TC、FFA及血清ALT、TG、TC、FFA含量升高,肝脏及血清CAT活性降低,肝脏PPARα及PPARαmRNA和CYP7A1 mRNA的表达减少。与模型组比较,胆宁片能明显降低肝脏TG、TC、FFA,血清ALT、TG、TC、FFA含量(P<0.01),提高肝脏及血清CAT活性,提高肝细胞PPARα及PPARαmRNA和CYP7A1及CYP7A1 mRNA的表达(P<0.01),且优于阳性对照组熊去氧胆酸。结论:胆宁片对实验性高脂饮食性脂肪肝大鼠具有一定的治疗作用,其作用机制可能与其诱导PPARα及CYP7A1表达,促进肝脏摄取、氧化脂肪酸与胆固醇有关。

Effects of Danning tablets on expression of PPARα and CYP7A1 in rats with nonalcoholic fatty liver disease

AIM:To study the therapeutic effects of Danning tablets on the expression of peroxisome proliferator activated receptorα(PPARα)and cholesterol 7 alpha-hydroxylase(CYP7A1)in rats with nonalcoholic fatty liver disease.METHODS:Male SD rats were fed with a high-lipid diet for 9 wk to induce nonalcoholic fatty liver model.After 9 wk,the therapeutic group was administrated with Danning tablets(0.317 g·kg~(-1)·d~(-1), ig)for 5 wk,the positive control group was administrated with ursodeoxycholic acid(UDCA,35 mg·kg~(-1)·d~(-1), ig)for 5 wk.The hepatic fatty degeneration degree was determined by the contents of lipids in the rat liver with pathology methods.The free fatty acid(FFA),triglyceride(TG),total cholesterol(TC),catalase(CAT)of liver andTG,CAT,TC,FFA,alanine aminotransferase(ALT),total bile acid(TBA)of blood,the expression of PPARαand CYP7A1 were measured by real-time fluorescent PCR and immunohistochemistry methods. RESULTS:High-lipid diet increased the contents of TG,TC,FFA in liver and ALT,TG,TC,FFA in serum and decreased the expression of the PPARαmRNA and CP7A1 mRNA significantly.Compared with the model group and the positive control group,Danning tablets decreased the contents of FFA,TG,TC in liver and TG,TC,ALT,FFA,TBA in serum and increased the PPARαmRNA and CYP7A1 mRNA expression remarkably(P<0.01).CONCLUTION:Danning tablets is effective in treating rat nonalcoholic fatty liver by inducing PPARαmRNA and CYP7A1 mRNA expression and promoting liver intake and oxidation of fatty acid.