[1]刘波,吴小翎,张霞,等.福辛普利对非酒精性脂肪性肝炎大鼠肝纤维化的作用[J].第三军医大学学报,2012,34(16):1646-1650.
 Liu Bo,Wu Xiaoling,Zhang Xia,et al.Effects and mechanism of fosinopril on hepatic fibrosis in rats with nonalcoholic steatohepatitis[J].J Third Mil Med Univ,2012,34(16):1646-1650.
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福辛普利对非酒精性脂肪性肝炎大鼠肝纤维化的作用(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
34卷
期数:
2012年第16期
页码:
1646-1650
栏目:
论著
出版日期:
2012-08-30

文章信息/Info

Title:
Effects and mechanism of fosinopril on hepatic fibrosis in rats with nonalcoholic steatohepatitis
作者:
刘波吴小翎张霞张伟吴蓉肖晓秋张凤周华梅王璐璐
重庆医科大学附属第二医院消化内科;重庆医科大学生命科学研究院
Author(s):
Liu Bo Wu Xiaoling Zhang Xia Zhang Wei Wu Rong Xiao Xiaoqiu Zhang Feng Zhou Huamei Wang Lulu
Department of Gastroenterology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010; College of Life Sciences, Chongqing Medical University, Chongqing, 400016, China
关键词:
福辛普利非酒精性脂肪性肝炎肝纤维化瘦素脂联素
Keywords:
fosinopril nonalcoholic steatohepatitis hepatic fibrosis leptin adiponectin
分类号:
R575.1;R969;R975.5
文献标志码:
A
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。
Abstract:
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 gavage) 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), triglycerides (TG), low-density lipoprotein (LDL), transforming growth factor-β (TGF-β), hyaluronic 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 collagen I 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 adiponectin 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.

参考文献/References:

刘波, 吴小翎, 张霞, 等. 福辛普利对非酒精性脂肪性肝炎大鼠肝纤维化的作用[J].第三军医大学学报,2012,34(16):1646-1650.

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更新日期/Last Update: 2012-07-29