替米沙坦对大鼠非酒精性脂肪肝纤维化的抑制作用

发布时间：2018-07-12 13:26

  本文选题：替米沙坦 + 肝纤维化　； 参考：《延边大学》2014年硕士论文

【摘要】：目的：探讨替米沙坦(telmisartan, Tel)对大鼠非酒精性脂肪性肝纤维化(non-alcoholic fatty liver fibrosis, NAFLF)的抑制作用。 方法：将同系60只Wistar大鼠随机分为6个组,每组10只。其中两组(共20只)用含胆碱的氨基酸(choline-supplemented L-amino acid-defined, CSAA)饲料喂养,CSAA组只喂养CSAA饲料,CSAA治疗组饲料中添加2.5mg/kg体重/天的替米沙坦。剩余4组(共40只)用胆碱缺乏的氨基酸(choline-deficient L-amino acid-defined, CDAA)饲料喂养,添加不同浓度的替米沙坦,使大鼠进食替米沙坦量分别为0(CDAA组)、0.5(低浓度组)、1.0(中浓度组)和2.5mg/kg体重/天(高浓度组),共喂养10周。用常规方法检测血清生化指标。用偶氮卡红(Azan)染色证明肝脏纤维化形成,用免疫组化法观察肝组织α-平滑肌激动蛋白(α-smooth muscle actin, α-SMA)和转化生长因子-β1(transforming growth factor-α1, TGF-β1)的表达;实时定量PCR法测定Ⅰ型前胶原(type Ⅰ procollagen)、金属基质蛋白酶(matrix metalloproteinases, MMPs)及其抑制物(tissue inhibitor of metalloproteinases, TIMPs)的表达。 结果：CDAA组血浆中的总胆汁酸,透明质酸,碱性磷酸酶,γ-谷氨酰转肽酶及总胆红素均高于CDAA添加替米沙坦组(P0.05或P0.01)；Azan染色表明,CDAA组大鼠肝组织有较明显的肝纤维化形成；肝组织α-SMA阳性细胞面积定量分析表明,低剂量组、中剂量组和高剂量组分别为7.65±1.12%,7.04±0.98%和4.76±0.52%,而CDAA组为10.38±2.17%,与CDAA组比较,均P0.01；TGFβ1宀量的图像分析表明在添加了替米沙坦的大鼠肝脏表达TGFβ1的量呈剂量依赖性的减少。CDAA组的type I前胶原表达明显高于替米沙坦添加组,且随着替米沙坦剂量的增加,其表达逐渐减少；同时MMP-13表达上升,而MMP-2,9和TIMP-1,2的表达下降；替米沙坦还表现为控制CDAA喂养大鼠的体重增加。 结论：替米沙坦能控制体重,减轻肝脏脂肪变性。可以通过抑制肝星状细胞的活化来阻止非酒精性脂肪肝纤维化的形成,有望成为控制非酒精性脂肪性肝病发展的很有前景的药物。
[Abstract]:Aim: to investigate the inhibitory effect of telmisartan (Tel) on non alcoholic fatty liver fibrosis (non-alcoholic fatty liver fibrosis, NAF LF) in rats. Methods: sixty Wistar rats of the same lineage were randomly divided into 6 groups with 10 rats in each group. Two groups (20 rats) were fed with choline-supplemented L-amino acid defined (CSAA) diet. The CSAA group was fed only 2.5mg/kg body weight / day telmisartan. The remaining 4 groups (40 rats) were fed with choline-deficient L-amino acid defined (CDAA) diet and were fed with different concentrations of telmisartan. The amount of telmisartan was 0 (CDAA group) 0.5 (low concentration group) and 1.0 (medium concentration group) and 2.5mg/kg body weight / day (high concentration group) were fed for 10 weeks. Serum biochemical indexes were detected by routine method. The expression of 伪 -smooth muscle activin (伪 -SMA) and transforming growth factor- 尾 1 (transforming growth factor- 伪 1 (TGF- 尾 1) in liver tissue was observed by immunohistochemical method. The expression of 伪 -smooth muscle activin (伪 -SMA) and transforming growth factor 尾 1 (transforming growth factor- 伪 1 (TGF- 尾 1) were detected by (Azan) staining. The expression of type 鈪，

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