摘要
目的观察厄贝沙坦对高脂饲养脂肪肝大鼠肝脏过氧化脂质体增殖激活受体γ(PPARγ)表达和胰岛素抵抗(IR)的影响,探讨其防治非酒精性脂肪性肝病(NAFLD)的可能机制。方法 45只雄性SD大鼠随机均分为空白对照组(普通饲料)、模型组(高脂饲料)和厄贝沙坦组[高脂饲料+50 mg/(kg·d)厄贝沙坦灌胃]。干预8周后观察各组大鼠肝指数、肝功能、血脂、稳态模型评价胰岛素抵抗指数(HOMA-IR)以及肝组织病理学变化,分别采用RT-PCR法和Western blot法检测各组大鼠肝组织PPARγmRNA和蛋白含量。结果饲养8周后模型组和厄贝沙坦组肝指数均较空白对照组显著增加(P<0.05),厄贝沙坦组体肝指数较模型组显著下降(P<0.05)。饲养4、6、8周后,模型组大鼠HOMA-IR(lg)逐渐增高(P<0.05)。饲养8周后,空白对照组、模型组和厄贝沙坦组肝脏炎症活动度计分比较差异均有统计学意义(P<0.05)。饲养8周后空白对照组、模型组和厄贝沙坦组大鼠肝组织PPARγmRNA和蛋白含量比较差异均有统计学意义(P<0.05)。模型组大鼠肝组织PPARγmRNA含量(r s=-0.823)及蛋白含量(r s=-0.608)与HOMAIR呈显著负相关(P<0.05)。结论厄贝沙坦可在一定程度上改善高脂饲养大鼠的脂肪肝和IR,可能与激活PPARγ有关。
Objective To investigate the effects of irbesartan on expression of peroxisome proliferator-activated receptor gamma （PPARγ） and insulin resistance （IR） in liver steatosis of rats on high-fat diet. Methods Forty-five SD rats were randomly divided into control group （normal diet and intragastric distilled water） , model group （highz fat diet and intragastrie distilled water） and irbesartan group [ high-fat diet and intragastrie irbesartan, 50 mg/（ kg · d） ]. The levels of alanine transaminase, aspartate transaminase, triglyceride, total cholesterol, homeostasis model assessment-insulin resistance （HOMA-IR） , liver index and liver histological characteristics were examined. The RT-PCR and Western blot were used to detect the expression of PPARγmRNA and protein, respectively in hepatic tissues of rats. Results At the end of the 8th week, liver index of rats in model group and irbesartan group increased significantly than that in control group, while that of irbesartan group decreased significantly than model group （ P 〈 0. 05 ）. The HOMA-IR in model group gradually increased during the 8 weeks of high-fat diet. At the end of the 8th week, the rats in both model group and irbesartan group developed fatty liver, nevertheless the degrees of fatty liver and hepatic inflammatory activity in irbesartan group were less than those in model group. The levels of PPAR＇y mRNA and protein in hepatic tissues of control group, model group, and irbesartan group were 1.59±0. 13 and 0.33 ±0.07, 0.53 ±0. 12 and 0. 12 ±0.03, 0.77 ±0. 14 and 0.23 ±0.08, respectively. In model group, HOMA-IR was negatively correlated with the levels of PPARγ mRNA and protein in hepatic tissues （rs = - 0. 823, P 〈 0. 05 ; rs = - 0. 608, P 〈 0.05, respectively）. Conclusion Irbesartan may improve fatty liver and IR of NAFLD rats with a mechanism of up-regulating PPARγ.
出处
《安徽医科大学学报》
CAS
北大核心
2013年第12期1429-1433,共5页
Acta Universitatis Medicinalis Anhui
基金
福建省卫生厅青年科研基金(编号:20090219)
福建省自然基金(编号:2009D062)
作者简介
作者简介：陈靖，男，副主任医师；
朱月永，男，副教授，主任医师，硕±生导师，责任作者，E-mail：ezhu066@sina．com
