Effects Of Captlpril On Proliferation, Type Ⅰ Collage And TIMP-1 In Rat Hepatic Stellate Cells

Backgroud/PurposeLiver fibrosis is a common pathological change appearing in the occurrence and development of various kinds of chronic liver diseases, and its research is increasingly paid more attention to by people. It has been known that rennin angiotensin aldosterone system (RAAS) plays a key role in the fibrogenesis of local tissue. Angiotensin II (Ang II) ,the principal effector molecules of the RAAS, exert local effects on cell growth and fibrogenesis. In recent years, much attention has been focused on the novel relationship between activation of RAAS and fibrosis of liver. Ang II can stimulate hepatic stellate cell (HSC) and increase the production of extracelluar matrix (ECM) .Hepatic fibrosis can be relieved by use of angiotensin-converting enzyme inhibitor(ACEI)and Angiotensin II type-l receptor (AT-1 receptor). However, the mechanisms underlying effects of Ang II on hepatic fibrogenesis remain fully be elucidated. There are a few reports about the investigation of this field can be found so far.This study aim to investigate the effects and mechanisms of captlpril on rat hepatic stellate cells by detect the expression of Col-Ⅰand TIMP-1 mRNA with molecular biology and cell proliferation.MethodsHSC-T6 rat hepatic stellate cell line was chosen as the study model of the activated HSC.Hepatic stellate cells were cultured in medium containing different concentrations of AngII and AngII +captlpril(1×10-5,1×10-7,1×10-9 respctively),cells were collected at 24 h.The cell growth and proliferation were assessed via MTT assay at different concentration.Total RNA of HSC were extracted and Col-I,TIMP-1 gene expressions levels was detected by reverse transcription polymerase chain reaction(RT-PCR). GAPDH was selected as internal standard control and the ration of two area light degree was used as the relative expression of mRNA.Date were presented as X±s ,comparisons among three or more groups were made by one way ANOVA followed by Dunnott's t test P<0.05 was considered statistically significant.ResultAngiotensinⅡ(1×10-9 to 1×10-5mmol/L)stimulated HSC proliferation as demonstrated by MTT assay. Captlpril had significant inhibitory effect on HSC growth at the concentration of 1×10-9 to 1×10-5mmol/L. The collagen-ⅠmRNA expression level of AngⅡgroup(0.850±0.107)was higher than that of control group(0.538±0.061), AngⅡ+captlpril (0.650±0.087)was lower than that of AngⅡgroup(0.850±0.107). The TIMP-1mRNA expression level of AngⅡgroup (1.145±0.219) was higher than that of control group(0.523±0.056), AngⅡ+captlpril (0.740±0.089) was lower than that of AngⅡgroup(1.145±0.219).ConclusionRapid proliferation of hepatic stellate cells occurs in response to AngiotensinⅡtreatment,but is inhibited after with the Captlpril.AngⅡcan increase the Col-I,TIMP-1 mRNA expression of HSC,but these effects may be inhibited by Captlpril.Therefore,It is thought that the Angiotensin may play an important role in the activation, transformation of HSC. Angiotensin-converting enzyme inhibitor(ACEI) may provide a new ways for the prevention and treatment of liver fibrosis.