白细胞介素-6/信号传导与转录激活因子3信号通路在乙醇性肝纤维化性别差异中的作用研究  

Role of interleukin-6/signal transduction and transcriptional activator 3 signaling pathway in sex difference of alcoholic liver fibrosis

作　　者：洪晓敏 李三强[1,2] 王子怡 李前辉[3] 程维刚 罗仁利 杨孟利 冯淑雅 吴俊菲 HONG Xiao-minl;LI San-qiang;WANG Zi-yi;LI Qian-hui;CHENG Wei-gang;LUO Ren-li;YANG Meng-li;FENG Shu-ya;WU Jun-fei(College of Basic Medicine and Law,HenanUniversityof Science and Technology,Luoyang 471000,Henan Province,China;Key Laboratory of Molecular Medicine for Liver Injury and Repair,HenanUniversityof Science and Technology,Luoyang 471000,Henan Province,China;Department of Anesthesiology,The FirstAffiliated Hospital of Henan University of Science andTechnology,Luoyang 471000,Henan Province,China)

机构地区：[1]河南科技大学,基础医学与法医学院,河南洛阳471000 [2]河南科技大学,肝脏损伤与修复分子医学重点实验室,河南洛阳471000 [3]河南科技大学第一附属医院麻醉科,河南洛阳471000

出　　处：《中国临床药理学杂志》2023年第10期1456-1460,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(82170606);中原科技创新领军人才计划基金资助项目(214200510004);洛阳市科技计划基金资助项目(2101030A,2022058Y);河南省高等学校重点科研项目计划基础研究专项基金资助项目(23ZX006)。

摘　　要：目的研究白细胞介素-6/信号传导与转录激活因子3(IL-6/STAT3)信号通路在乙醇性肝纤维化性别差异中的作用。方法选择7~8周龄的C57BL/6N雌鼠和雄鼠各50只进行随机分为雌性对照组、雌性模型组、雄性对照组和雄性模型组,每组各25只。对照组用TP4030C Lieber-DeCarli液体饲料喂养8周,模型组用TP4030A Lieber-DeCarli液体饲料喂养8周,并且联合31.5%乙醇灌胃,剂量为5 g·kg^(-1),每周2次。用试剂盒检测各组小鼠的血清谷丙转氨酶(GPT)、谷草转氨酶(GOT)酶活性和雌二醇(E_(2))、睾酮(T)浓度的变化,用天狼星红染色检测各组小鼠纤维化情况,用蛋白质印迹法检测IL-6/STAT3通路相关蛋白的表达水平。结果雌性对照组、雌性模型组、雄性对照组和雄性模型组的GPT酶活性分别为(8.46±3.30)、(49.65±17.35)、(9.96±3.29)和(82.44±10.76)U·L^(-1),GOT酶活性分别为(28.05±6.28)、(62.15±12.12)、(26.94±3.89)和(105.70±13.43)U·L^(-1),E2分别为(89.49±22.35)、(37.12±9.34)、(14.49±4.95)和(7.31±2.47)pg·mL^(-1),T分别为(3.55±2.33)、(0.75±0.30)、(106.10±22.52)和(47.60±7.86)ng·mL^(-1),胶原纤维光密度值分别为68.87±5.75、191.30±7.72、78.07±12.00和246.70±9.29,α-平滑肌肌动蛋白相对表达水平分别为1.00±0.00、1.36±0.26、1.18±0.13和1.61±0.17,IL-6蛋白相对表达水平分别为1.00±0.00、1.93±0.54、1.34±0.14和4.13±0.83,IL-6受体(IL-6R)蛋白相对表达水平分别为1.00±0.00、2.17±0.51、1.39±0.45和2.58±0.61,磷酸化STAT3蛋白相对表达水平分别为1.00±0.00、2.94±0.14、1.34±0.18和3.60±0.88。对照组的上述指标与模型组比较,差异均有统计学意义(P<0.05,P<0.01);雄性模型组的上述指标与雌性模型组比较,差异均有统计学意义(P<0.05,P<0.01)。结论在小鼠乙醇性肝纤维化中,与雌性小鼠相比,雄性小鼠肝中IL-6的水平显著升高,IL-6与可溶性受体IL-6R形成复合物,胞内STAT3聚集和磷酸化增多,进一步激活IL-6/STATObjective To investigate the role of interleukin-6/signaling and activator of transcription 3(IL-6/STAT3)signaling pathway in sex differences in alcoholic liver fibrosis.MethodssFifty female and male C57BL/6N mice aged 7-8 weeks were selected and randomly divided into female control group,female model group,male control group and male model group,25 rats in each group.The control group was fed with TP4030C Lieber-DeCarli liquid diet for 8 weeks,and the model group was fed with TP4030A Lieber-DeCarli liquid diet for 8 weeks and combined with 31.5%ethanol by gavage at a dose of 5 g·kg^(-1)twice a week.The changes of serological glutamic-pyruvic transaminase(GPT)and glutamic oxaloacetic transaminase(GOT)enzyme activities and estradiol(E_(2))and testosterone(T)concentrations in each group of mice were measured by kits,fibrosis in each group was detected by Sirius red staining,and the expression of factors related to IL-6/STAT3 pathway was detected by protein bltting.Results GPT enzyme activities of female control,female model,male control and male model groups were(8.46±3.30),(49.65±17.35),(9.96±3.29)and(82.44±10.76)U.L^(-l);GOT enzyme activities were(28.05±6.28),(62.15±12.12),(26.94±3.89)and(105.70±13.43)U·L^(-1)Ez levels were(89.49±22.35),(37.12±9.34),(14.49±4.95)and(7.31±2.47)pg·mL^(-1);Tlevels were(3.55±2.33),(0.75±0.30),(106.10±22.52)and(47.60±7.86)ng·mL^(-1);collagen fiber optical density values were 68.87±5.75,191.30±7.72,78.07±12.00 and 246.70±9.29;the relative expression levels ofα-smooth muscle actin protein were 1.00±0.00,1.36±0.26,1.18±0.13 and 1.61±0.17;the relative expression levels of IL-6 protein were 1.00±0.00,1.93±0.54,1.34±0.14 and 4.13±0.83;the relative expression levels of IL-6 receptor(IL-6R)protein were 1.00±0.00,2.17±0.51,1.39±0.45 and 2.58±0.61;the relative expression levels of phosphorylated STAT3 protein were 1.00±0.00,2.94±0.14,1.34±0.18 and 3.60±0.88,respectively.The differences of above indices were statistically significant between the control gr

关 键 词：乙醇性肝纤维化 性别差异 性激素 α-平滑肌肌动蛋白 白细胞介素-6/信号传导与转录激活因子3信号通路 

分 类 号：R97[医药卫生—药品]