摘要
目的探讨福辛普利对高脂饮食诱导的非酒精性脂肪性肝炎大鼠肝纤维化的作用,以及对瘦素和脂联素血清水平和在白色脂肪组织中基因表达水平的影响。方法将40只健康雄性Sprague Dawley(SD)大鼠适应性饲养1周后,随机分为正常对照组(NC组,普通饮食+生理盐水灌胃)、模型组(HC组,高脂饮食+生理盐水灌胃)、药物对照组[NF组,普通饮食+福辛普利3.6 mg/(kg.d)灌胃]和药物干预组[HF组,高脂饮食+福辛普利3.6 mg/(kg.d)灌胃],每组10只。喂养24周后处死,检测各组大鼠谷丙转氨酶(ALT)、谷草转氨酶(AST)、甘油三酯(triglycerides,TG)、低密度脂蛋白(low-density lipoprotein,LDL)、转化生长因子-β(transforming growth factor-β,TGF-β)、透明质酸(hyaluronic acid,HA)、瘦素和脂联素的血清水平,比较各组大鼠脂肪组织瘦素和脂联素mRNA水平以及肝组织的胶原蛋白(collagen)Ⅰ蛋白表达和病理改变。结果与HC组(ALT:91.30±30.71;TG:2.25±0.31;LDL:1.53±0.31;TGF-β:125.95±8.23;HA:165.72±29.13;瘦素:130.61±35.56;脂联素:5.97±2.19)相比,HF组血清ALT(50.20±12.13,P<0.05)、TG(1.09±0.34,P<0.01)、LDL(1.16±0.13,P<0.05)、TGF-β(72.55±23.2,P<0.01)、HA(90.13±27.42,P<0.01)和瘦素(31.74±36.35,P<0.05)水平显著降低,脂联素(21.60±8.43,P<0.01)水平显著升高;脂肪组织的脂酸素mRNA水平显著升高,而瘦素的mRNA水平变化无显著意义(P>0.05);肝组织collagenⅠ蛋白表达显著降低(P<0.05);福辛普利能减轻肝细胞脂肪变性、炎症浸润和纤维化程度。结论福辛普利可能通过下调血清瘦素水平,上调脂联素的血清水平和其在脂肪组织的基因表达,对非酒精性脂肪性肝炎大鼠具有保肝和抗肝纤维化作用。
Objective To investigate the effects of fosinopril on hepatic fibrosis, plasma levels of leptin and adiponectin and their mRNA expression in white adipose tissues in rats with nonalcoholic steatohepatitis induced by high-fat diet （HFD）. Methods A total of 40 health male Sprague Dawley （SD） rats were fed with normal feed for 1 week to adapt to vivarium conditions, and then were randomized into four experimental groups （n =10） ： a NC group （normal feed and normal saline by gavage）, a HC group （HFD and normal saline by gavage） , a NF group （normal feed and fosinopril 3.6 mg/kg body weight/day by garage ） and a HF group （HFD and fosinopril 3.6 mg/kg body weight/day by gavage）. All the rats were sacrificed after fed for 24 weeks. The serum levels of alanine aminotransferase （ ALT）, aspartate aminotransferase （ AST）, triglyeerides （TG）, low-density lipoprotein （LDL）, transforming growth factor-β （TGF-β）, hyaluronie acid （HA）, leptin and adiponectin were determined. The mRNA expression of leptin and adiponectin in white adipose tissues, collagen Ⅰ expression in hepatic tissues and histological changes were measured and compared among the four groups. Results As compared with the HC group （ALT： 91.30±30.71; TG： 2.25 ±0.31; LDL： 1.53± 0.31; TGF-β：125.95±8.23; HA： 165.72±29. 13; leptin： 130.61±35.56 and adiponectin 5.97±2. 19）, the serum levels of ALT （50.20±12.13, P 〈0. 05）, TG （ 1.09±0.34, P 〈0.01 ）, LDL （ 1.16 ±0.13, P 〈0. 05）, TGF-β （72.55±23.2, P 〈0.01）, HA （90.13±27.42, P 〈0.01） and leptin （31.74± 36.35, P 〈 0.05 ） and hepatic collagenⅠ expression （P 〈 0.05 ） in the HF group were significantly reduced by fosinopril, but the serum level of adiponectin was elevated （21.60±8.43, P 〈 0. 01 ）. The adiponeetin mRNA expression in white adipose tissues was significantly higher in the HF group than in the HC group （P 〈 0. 001 ） , whereas the leptin mRNA expression was not affected （P 〉 0. 05 ）. The liver lobular inflammation score and hepatic fibrosis stage were lessened in the HF group as compared with the HC group. Conclusion Fosinopril may prevent hepatic fibrosis in rats with nonalcoholic steatohepatitis by reducing the serum level of leptin and elevating the serum level of adiponectin and its mRNA expression in white adipose tissues.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2012年第16期1646-1650,共5页
Journal of Third Military Medical University
