本文選題：替米沙坦 + 肝纖維化�。� 參考：《延邊大學》2014年碩士論文

【摘要】：目的：探討替米沙坦(telmisartan, Tel)對大鼠非酒精性脂肪性肝纖維化(non-alcoholic fatty liver fibrosis, NAFLF)的抑制作用。 方法：將同系60只Wistar大鼠隨機分為6個組,每組10只。其中兩組(共20只)用含膽堿的氨基酸(choline-supplemented L-amino acid-defined, CSAA)飼料喂養(yǎng),CSAA組只喂養(yǎng)CSAA飼料,CSAA治療組飼料中添加2.5mg/kg體重/天的替米沙坦。剩余4組(共40只)用膽堿缺乏的氨基酸(choline-deficient L-amino acid-defined, CDAA)飼料喂養(yǎng),添加不同濃度的替米沙坦,使大鼠進食替米沙坦量分別為0(CDAA組)、0.5(低濃度組)、1.0(中濃度組)和2.5mg/kg體重/天(高濃度組),共喂養(yǎng)10周。用常規(guī)方法檢測血清生化指標。用偶氮卡紅(Azan)染色證明肝臟纖維化形成,用免疫組化法觀察肝組織α-平滑肌激動蛋白(α-smooth muscle actin, α-SMA)和轉化生長因子-β1(transforming growth factor-α1, TGF-β1)的表達;實時定量PCR法測定Ⅰ型前膠原(type Ⅰ procollagen)、金屬基質蛋白酶(matrix metalloproteinases, MMPs)及其抑制物(tissue inhibitor of metalloproteinases, TIMPs)的表達。 結果：CDAA組血漿中的總膽汁酸,透明質酸,堿性磷酸酶,γ-谷氨酰轉肽酶及總膽紅素均高于CDAA添加替米沙坦組(P0.05或P0.01)；Azan染色表明,CDAA組大鼠肝組織有較明顯的肝纖維化形成；肝組織α-SMA陽性細胞面積定量分析表明,低劑量組、中劑量組和高劑量組分別為7.65±1.12%,7.04±0.98%和4.76±0.52%,而CDAA組為10.38±2.17%,與CDAA組比較,均P0.01；TGFβ1宀量的圖像分析表明在添加了替米沙坦的大鼠肝臟表達TGFβ1的量呈劑量依賴性的減少。CDAA組的type I前膠原表達明顯高于替米沙坦添加組,且隨著替米沙坦劑量的增加,其表達逐漸減少；同時MMP-13表達上升,而MMP-2,9和TIMP-1,2的表達下降；替米沙坦還表現(xiàn)為控制CDAA喂養(yǎng)大鼠的體重增加。 結論：替米沙坦能控制體重,減輕肝臟脂肪變性�？梢酝ㄟ^抑制肝星狀細胞的活化來阻止非酒精性脂肪肝纖維化的形成,有望成為控制非酒精性脂肪性肝病發(fā)展的很有前景的藥物。
[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 偽 -smooth muscle activin (偽 -SMA) and transforming growth factor- 尾 1 (transforming growth factor- 偽 1 (TGF- 尾 1) in liver tissue was observed by immunohistochemical method. The expression of 偽 -smooth muscle activin (偽 -SMA) and transforming growth factor 尾 1 (transforming growth factor- 偽 1 (TGF- 尾 1) were detected by (Azan) staining. The expression of type 鈪，

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