血管紧张素Ⅱ及其受体拮抗剂对肝星状细胞收缩的影响

Effects of angiotensin II and its receptor antagonist on contraction of hepatic stellate cells

目的观察血管紧张素Ⅱ及其受体拮抗剂对体外培养的肝星状细胞收缩的影响。方法采用HSC-T6肝星状细胞系作为活化的肝星状细胞的研究模型。将培养的肝星状细胞随机分为对照组、血管紧张素Ⅱ(1×10-9～1×10-5)mol／L组、受体拮抗剂组和血管紧张素Ⅱ+受体拮抗剂组,继续培养48 h后,比较胶原晶格收缩面积的变化,并绘制收缩的量效关系曲线和时效关系曲线。结果血管紧张素Ⅱ各浓度组,胶原晶格的收缩面积比较对照组均明显增加(P<0．05)。随着血管紧张素Ⅱ浓度的升高,胶原晶格的收缩面积逐渐增大,量效曲线呈近似直线的正相关关系;而且随着血管紧张素Ⅱ作用时间的延长,胶原晶格的收缩面积逐渐增大,在48 h之内呈时间依赖性。血管紧张素Ⅱ作用48 h后,胶原晶格面积为(379．337±37．755)mm2,同时加入受体拮抗剂,面积为(540．803±70．018)mm2,胶原晶格的收缩程度比较血管紧张素Ⅱ组明显减轻(P<0．05)。结论血管紧张素Ⅱ能够剂量依赖性和时间依赖性地促进肝星状细胞的收缩,而血管紧张素Ⅱ1型受体拮抗剂能够抑制血管紧张素Ⅱ引起的肝星状细胞的收缩。

Objective To investigate the effects of angiotensin Ⅱ （Ang Ⅱ ） and angiotensin Ⅱ type Ⅰ receptor antagonist （AT1RA） on contraction of in vitro cultured hepatic stellate cells （HSCs）. Methods HSC-T6 hepatic stellate cell line was chosen as the study model of the activated hepatic stellate cells. Cultured HSCs were randomized into the control group, Ang Ⅱ（1 ×10^-9 -1 × 10^-5 ）mol/ L groups, AT1RA group and Ang Ⅱ ＋ AT1RA group. The effects of Ang Ⅱ and AT1RA on the hepatic stellate cell contraction were studied by the contraction area of collagen lattice after 48 h. Meanwhile, the dose-effect and time-effect curves were established. Results As compared with the control group, Ang Ⅱ significantly elicited collagen lattice contraction （P〈0. 05）. The contractive area of collagen lattice increased along with the concentration of Ang Ⅱ and the dose-effect curve had a positive correlation like a straight line. The contractive area of collagen lattice increased along with the prolongation of Ang Ⅱ action time and the time-effect curve showed the time-dependent manner in 48 h. The levels of the collagen lattice area after 48 h in Ang Ⅱ group and Ang Ⅱ ＋AT1RA group were 379.337＋37.755 mm^2 and 540.803＋70.018 mm^2, respectively. ATIRA markedly decreased the contraction of collagen lattice induced by Ang Ⅱ （P〈0. 05）. Conclusions Ang Ⅱ can increase the contraction of hepatic stellate cells in a dose- and time-dependent manner while AT1RA inhibits the contraction of hepatic stellate cells induced by Ang Ⅱ.