Objective: To investigate the effects of angiotensin II type 1 receptor antagonist valsartan on leptin, leptin receptor and collagen in rats with hepatic fibrosis. Methods: Thirty-six male wistar rats were randomly divided into control group, model group and drug-treated group, with 12 rats in each group. Liver fibrosis models were made by subcutaneous injection of carbon tetrachloride on the dorsal of the rats, simultaneously gastric gavage with Valsartan and were killed at the end of 8th week. The degree of liver fibrosis was observed by HE and Masson staining. The serum leptin (LP) and TGFβ1 were determined by ELISA. Liver LP mRNA and leptin receptor mRNA (OB-R mRNA) were detected by RT-PCR. Liver LP, OB-R and collagen I were detected by Western blot. The data of multiple groups were analyzed by one-way analysis variance (ANOVA), and linear correlation was performed between serum LP and TGF β1. Results: After the intervention of valsartan, HE and Masson staining showed that the degree of liver fibrosis was significantly reduced. The levels of serum LP and TGFβ1 in the control group were (18.92 ± 7.10) ng/ml and (9.13 ± 1.58) pg/ml respectively, which were significantly lower than those in the model group (46.92 ± 28.54) ng/ml and (16.39 ± 3.56) pg/ml, And (29.27 ± 7.27) ng/ml and (12.24 ± 2.94) pg/ml in the drug-treated group, respectively. The F values were 7.864 and 20.057 respectively. The P values were < 0.05. The differences were statistically significant. The relative expression levels of LP and OB-R mRNA in the control group were 0.35 ± 0.18 and 0.62 ± 0.18, respectively, which were significantly lower than those in the model group (1.79 ± 1.79 and 1.52 ± 1.44, and drug-treated group 0.48 ± 0.34 and 0.75 ± 0.26, respectively), F values = 6.914,3.894, P values were < 0.05, the differences were statistically significant. The relative expression levels of LP, OB-R and collaten I in liver were 0.71 ± 0.13, 0.81 ± 0.11 and 0.76 ± 0.13 in the model group, 0.97 ± 0.06, 1.04 ± 0.06, and 1.05 ± 0.04 respectively in the drug-treated group and 0.74 ± 0.05, 0.93 ± 0.05 and 0.91 ± 0.05. The F values were 15.425, 13.757 and 19.130 respectively in three groups (P < 0.001), the difference was statistically significant. Conclusion: Valsartan, an angiotensin II type 1 receptor antagonist, can reduce the expression of leptin and leptin receptor, reduce the production of TGFβ1 and collaten I, and play an anti-hepatic fibrosis effect.
目的： 探讨血管紧张素Ⅱ1型受体拮抗剂缬沙坦对肝纤维化大鼠瘦素、瘦素受体及胶原表达的影响。 方法： 36只Wistar雄性大鼠随机分为对照组、模型组、药物组，每组12只，四氯化碳背部皮下注射法造肝纤维化模型，药物组于造模开始缬沙坦灌胃，8周末处死。肝组织HE和Masson染色观察肝纤维化程度。酶联免疫吸附法测定血清瘦素（LP）、转化生长因子β1（TGFβ1）浓度，逆转录PCR检测肝组织LP mRNA、瘦素受体（OB-R）mRNA水平，Western blot检测肝脏LP、OB-R、Ⅰ型胶原（collagenⅠ）蛋白表达。多组间数据采用单因素方差分析，血清LP与TGFβ1行线性相关分析。 结果： 缬沙坦干预后肝组织HE和Masson染色显示纤维化程度明显减轻。对照组大鼠血清LP、TGFβ1水平分别为（18.92±7.10）ng/ml、（9.13±1.58）pg/ml，与模型组的（46.92±28.54）ng/ml、（16.39±3.56）pg/ml，及药物组的（29.27±7.27）ng/ml、（12.24±2.94）pg/ml比较，F值分别为7.864和20.057，P值均< 0.05，差异均有统计学意义。对照组肝脏LP、OB-R mRNA相对表达量分别为0.35±0.18、0.62±0.18，与模型组的1.79±1.79、1.52±1.44，及药物组的0.48±0.34、0.75±0.26比较，F值分别为6.914、3.894，P值均< 0.05，差异均有统计学意义。肝脏LP、OB-R、collagenⅠ蛋白相对表达量：对照组分别为0.71±0.13、0.81±0.11、0.76±0.13，模型组分别为0.97±0.06、1.04±0.06、1.05±0.04，药物组分别为0.74±0.05、0.93±0.05、0.91±0.05，三组比较，F值分别为15.425、13.757、19.130，P值均< 0.001，差异均有统计学意义。 结论： 血管紧张素Ⅱ1型受体拮抗剂缬沙坦可降低肝纤维化大鼠瘦素、瘦素受体的表达，减少TGFβ1、collagenⅠ的产生，发挥抗肝纤维化的作用。.
Keywords: Angiotensin II; Leptin; Liver cirrhosis; Obgene receptor; Valsartan.