Urantide对动脉粥样硬化大鼠脂肪肝组织中STAT3磷酸化的影响

Effect of urantide on the phosphorylation of STAT3 in the fatty livers of atherosclerotic rats

目的:探讨尾加压素Ⅱ受体拮抗剂Urantide对动脉粥样硬化(atherosclerosis,AS)大鼠脂肪肝组织中信号转导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)表达的影响。方法:30只雄性Wistar大鼠随机分为正常组、AS组、Urantide组。AS组和Urantide组均给予腹腔注射维生素D3(vitamin D3,VD3)150μg/(kg·d)连续3 d,并饲喂高脂饲料诱导AS,Urantide组在造模成功后给予尾静脉注射Urantide 30μg/(kg·d)连续2周。测量各组大鼠体重及肝重,计算肝系数;HE染色观察大鼠胸主动脉、肝的形态学改变;生化检测大鼠血清中丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)的含量。RT-qPCR方法检测肝脏STAT3 mRNA表达水平;免疫印迹检测肝脏STAT3、p-STAT3蛋白水平;免疫荧光法检测肝细胞中p-STAT3水平。结果:与正常组相比,AS组大鼠胸主动脉出现典型的AS病理学改变,肝出现典型的脂肪变性,AS组大鼠肝系数、血清ALT、AST含量以及肝p-STAT3的蛋白水平显著升高。与AS组相比,Urantide组大鼠AS病变和肝脂肪变性明显减轻;大鼠肝系数、血清ALT、AST含量以及肝p-STAT3水平显著降低。各组大鼠肝中STAT3的mRNA及蛋白表达水平无显著变化。结论:Urantide可通过抑制STAT3的活化缓解肝损伤,治疗脂肪肝。

Objective:To investigate the effect of urantide,a urotensin Ⅱ receptor antagonist,on the phosphorylation of signal transducers and activators of transcription(STAT3)expression in the fatty liver of atherosclerosis(AS)rats. Methods:A total of 30 male Wistar rats were randomly divided into three groups:control group,AS group and Urantide group. The AS group and Urantide group were induced by an intraperitoneal injection of vitamin D3(VD3)150 μg/(kg·d)for 3 days and by feeding with special high fat food. Following successful modeling,the Urantide group was given urantide 30 μg/(kg·d)for 2 weeks by tail vein injection. The body weight and liver weight of each rat were measured to calculate the liver index. HE staining was used to observe the morphological change of the thoracic aortae and livers of the rats. Biochemical indexes were measured by detecting the change of alanine transaminase(ALT)and aspartate aminotransferase(AST)in the serum of rats. The expression levels of STAT3 mRNA in liver tissues were detected by RT-qPCR. The levels of STAT3 and p-STAT3 protein in liver tissues were detected by Western blot. Immunofluorescence was used to detect the levels of p-STAT3 in the hepatocytes of each group. Results:Compared with the control group,the HE staining of the AS group showed typical AS pathological change of thoracic aortae and typical steatosis of the livers;the liver indexes,the levels of ALT,AST in the serum and the level of p-STAT3 in the livers increased significantly in the AS group. Compared with the AS group,the AS pathological changes and the steatosis of the livers in the Urantide group were significantly alleviated;the liver indexes,the levels of ALT,AST in the serum and the level of p-STAT3 in the livers decreased significantly in the Urantide group. In addition,no significant changes were observed in the expression levels of STAT3 mRNA and protein in the liver tissues of each group. Conclusion:Urantide can alleviate liver injury by inhibiting the activation of STAT3 in the treatment of fatty liver.