辛伐他汀和非诺贝特对非酒精性脂肪肝大鼠血清ATGL酶活性和TNF-α水平的影响  

Effect of simvastatin and fenofibrate on serum adipose triglyceride lipase and TNF-α levels in rats with non-alcoholic fatty acid liver disease

作　　者：何微[1] 喻陆[2] 高德禄[2] 张世俊[2] 

机构地区：[1]南方医科大学研究生学院,广州510515 [2]解放军第305医院,北京100017

出　　处：《解放军医学院学报》2013年第3期279-282,共4页Academic Journal of Chinese PLA Medical School

基　　金：解放军第305医院青年面上课题(10YD1)

摘　　要：目的观察辛伐他汀和非诺贝特在治疗大鼠非酒精性脂肪肝病(nonalcoholic fatty liver disease,NAFLD)过程中,大鼠血清脂肪甘油三酯脂酶(adipose triglyceride lipase,ATGL)活性和TNF-α水平的变化以及两者间的关系。方法 78只雄性SD大鼠随机分为正常对照组(15只)和NAFLD模型组(63只)。高脂饲料建立NAFLD大鼠模型,于12周末检测血脂,病理学证实造模成功后,将模型组随机分为4组:NAFLD对照组,辛伐他汀组,非诺贝特组和饮食组。16周末,处死所有动物,检测血清TG、TC、FBG、ALT、AST、BUN、Scr及ATGL和TNF-α水平,计算肝指数及观察肝脏病理变化。结果两药物组血清TNF-α水平分别为290±78,332±89,ATGL酶浓度分别为0.69±0.21,0.63±0.20,而NAFLD模型组TNF-α水平为485±115,ATGL酶浓度为0.43±0.22,两药物组血清TNF-α水平较模型组明显下降(P<0.05),而ATGL酶活性显著升高(P<0.01),且肝组织病理明显改善;饮食组血清TNF-α水平及ATGL酶浓度分别为432±102,0.52±0.19,两药物组血清ATGL和TNF-α水平较饮食组恢复显著(均P<0.05);NAFLD大鼠血清TNF-α与ATGL呈高度负相关(r=0.948,P<0.01)。结论 NAFLD大鼠血清ATGL酶活性与TNF-α高度相关;辛伐他汀和非诺贝特可通过降低TNF-α水平而增强ATGL酶活性有效治疗大鼠NAFLD。Objective To observe the effect of simvastatine and fenofibrate on adipose serum triglyceride lipase （ATGL） and TNF- a levels in rats with non-alcoholic fatty acid liver disease （NAFLD）. Methods Seventy-eight male SD rats were randomly divided into normal group（n=15） and NAFLD model group（n=63）. Rats in normal control group were fed with normal diet and those in NAFLD model group were fed with high-fat diet. Their serum TG and TC levels were measured at the end of 12 weeks. After a rat NAFLD model was established, the rats in NAFLD model group were randomly divided into NAFLD control group, simvastatine treatment group, fenofibrate treatment group, and diet group. The animals were killed and their serum TG, TC, ALT, AST, BUN, Scr, fasting blood glucose （FBG）, TNF- ct and ATGL levels were measured at the end 16 weeks, their liver index was counted, and their liver pathologic changes were observed. Results The serum TNF-a and ATGL levels were 290±78 and 332±89, 0.69±0.21 and 0.63 ± 0.20,485 ± 115 and 0.43± 0.22, respectively, in simvastatine treatment group, fenofibrate treatment group and NAFLD model group （P 〈 0.05, P 〈 0.01）. The liver pathological lesions were significantly improved in simvastatine treatment group and fenofibrate treatment group. The serum ATGL and TNF- a levels were significantly higher in diet group than in NAFLD control group（0.52 ± 0.19 vs 0.43±022,P 〈 0.05）. The serum TNF-a level was negatively related with the serum ATGL level（t=0.948, P 〈 0.01）. Conclusion Serum ATGL activity is closely correlated with serum TNF- a level in rats with NAFLD. Simvastatine and fenofibrate can increase the ATGL activity by decreasing the serum TNF- a level, thus effectively alleviating NAFLD.

关 键 词：非酒精性脂肪肝 脂肪甘油三酯脂酶 肿瘤坏死因子 辛伐他汀 非诺贝特 

分 类 号：R575.5[医药卫生—消化系统]