Inhibitory Effect Of Telmisartan On Non-Alcoholic Fatty Liver Fibrosis In Rats

AIM:To study the inhibitory effect of telmisartan (Tel) on non-alcoholic fatty liver fibrosis in rats.METHODS:Sixty Wistar rats were randomly and equally divided into6groups. 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 of2.5mg/kg body weight per day. The residual four groups fed with choline-deficient L-amino acid-defined (CDAA) diet and supplemented with Tel of0(CDAA),0.5(Tel-Low),1.0(Tel-Med) and2.5(TeI-High) mg/kg body weight per day. The total experimental period was10weeks. Serum biological parameters were determined routinely. Using Azan stain to check the extracellular matrix deposition. Expression of a-smooth muscle actin (a-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 level of total bile acid, hyaluronic acid, alkaline phosphatase, y-gluamyl transpeptidase and total bilirubin in serum of CDAA group were all higher than that of CDAA diet supplemented with Tel groups(P<0.05or P<0.01). The quantitative analysis of a-SMA positive cellular area showed as7.65±1.12%(Tel-Low),7.04±0.98%(Tel-Med),4.76±0.52%(Tel-High) vs10.38±2.17%(CDAA), all P<0.01; the quantity of TGF-β1decreased in a dose-dependent manner as supplemented Tel into CDAA diets compared with CDAA diet rats. The mRNA of type1procollagen was higher than that of the Tel treated rats, and that decreasing as the dose of Tel increasing; on the same time, the expression of MMP13increased, while the expression of MMP2,9and TIMP1,2decreased. Tel also controlled the CDAA diet rats body weight gain.CONCLUSIONS:Tel can attenuate weight gain, alleviating steatosis and Inflammation. Tel suppressed non-alcoholic fatty liver fibrosis in rats through inhibited HSCs activation, it may become a promising medicine to control non-alcoholic fatty liver disease.