关键词: 关键词 替米沙坦, 肝纤维化, 肝星状细胞, 非酒精性脂肪肝病

Abstract: Objective To study the inhibited effect of telmisartan (Tel) on non-alcoholic fatty liver fibrosis (NLFLF) in rats. Methods Sixty Wistar rats were randomly and equally divided into 6 groups. Two groups of them supplied with choline-supplemented L-amino acid-defined diet(CSAA) : CSAA group fed with CSAA diet only, CSAA treatment group fed with CSAA diet and supplemented with Tel of 2.5 mg/(kg BW?d)(CSAA+Tel-high). The residual four groups fed with choline-deficient L-amino acid-defined (CDAA) diet and supplemented with Tel of 0(CDAA), 0.5 (CDAA+Tel-low), 1.0(CDAA+Tel-med) and 2.5(CDAA+Tel-high) mg/(kg BW?d). The total experimental period was 10 weeks. Serum biological parameters were determined routinely. Expression of α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) in liver tissue were determined by immunohistochemistry, and pathological changes in liver tissues were detected by Azan staining. The messenger RNA (mRNA) expressions of type I procollagen, matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMPs) were evaluated using real-time quantitative PCR. Results The levels of hyaluronic acid, alkaline phosphatase, γ-gluamyl transpeptidase and total bilirubin in serum of CDAA group were all higher than those of CDAA diet supplemented with Tel (P <0.05 or P<0.01). The quantity of α-SMA and TGF-β1 was higher in CDAA rats compared with Tel treated rats(P<0.01). The mRNA of type I procollagen was higher than that of the Tel treated rats(P<0.01), and that decreasing as the dose of Tel increasing; on the same time, the expression of MMP13 increased, while the expression of MMP2,9 and TIMP1,2 decreased. Tel also controlled the CDAA diet rats body weight gain. Conclusions Tel suppressed NLFLF in rats through inhibited HSCs activation, it may become a promising medicine to control non-alcoholic fatty liver disease.

Key words: 关键词 telmisartan, liver fibrosis, hepatic stellate cell, non-alcoholic fatty liver disease