细胞信号转导抑制因子3下调对更年期雌性大鼠瘦素抵抗的影响  

Effect of down-regulation of cellular signal transduction inhibitor 3 on leptin resistance in menopausal female rats

作　　者：曲晨菲 张艳 张竞竞[1] 李元梦 周猛[1] 李秀艳[1] QU Chen-fei;ZHANG Yan;ZHANG Jing-jing;LI Yuan-meng;ZHOU Meng;LI Xiu-yan(Medical College,Qingdao Binhai University,Qingdao 266555,Shandong Province,China)

机构地区：[1]青岛滨海学院医学院,山东青岛266555

出　　处：《中国临床药理学杂志》2020年第5期521-524,共4页The Chinese Journal of Clinical Pharmacology

基　　金：山东省高等学校科技计划课题资助项目(J16LK53)。

摘　　要：目的探讨细胞信号转导抑制因子3(SOCS3)下调对更年期雌性大鼠瘦素抵抗的影响,及其对酪氨酸蛋白激酶2(JAK2)/信号传导子和转录激活子3(STAT3)和正磷脂酰肌醇3-激酶(PI3K)/蛋白质丝氨酸苏氨酸激酶(AKT)通路的影响。方法将SD大鼠随机分为空白对照组、假手术组、模型组、阴性对照组和实验组;模型组、阴性对照组和实验组均给予去势手术,假手术组仅分离卵巢不给予结扎和切除卵巢,空白对照组不给予任何处理。空白对照组、假手术组和模型组均于下丘脑弓状核处给予注射0.9%NaCl 2μL;阴性对照组于下丘脑弓状核处给予注射LV-negative 2μL;实验组于下丘脑弓状核处给予注射LV-shSOCS32μL。干预4周后,用放射免疫法测定大鼠血清瘦素含量,用酶联免疫吸附实验法检测血清SOCS3水平,用逆转录聚合酶链反应法检测下丘脑组织SOCS3 mRNA的表达水平,用Western blot法检测下丘脑组织JAK2/STAT3和PI3K/AKT信号通路相关蛋白的表达水平。结果实验组、模型组、阴性对照组、空白对照组和假手术组的血清瘦素分别为(1.58±0.22),(2.92±0.39),(2.88±0.34),(1.73±0.28)和(1.78±0.32)pg·mL^-1,血清SOCS3分别为(94.38±8.54),(177.93±15.06),(179.08±11.43),(123.08±12.73)和(119.42±18.05)pg·mL^-1,SOCS3 mRNA表示水平分别为(0.39±0.15),(1.43±0.23),(1.48±0.27),(0.62±0.16)和(0.58±0.12),p-JAK2/JAK2分别为(1.83±0.23),(0.48±0.16),(0.46±0.12),(1.45±0.18)和(1.51±0.27),p-STAT3/STAT3分别为(1.99±0.14),(0.64±0.18),(0.59±0.23),(1.73±0.24)和(1.68±0.28),p-AKT/AKT分别为(1.58±0.29),(0.56±0.17),(0.53±0.22),(1.32±0.31)和(1.33±0.26),p-PI3K/PI3K分别为(1.23±0.18),(0.36±0.09),(0.38±0.08),(0.92±0.09)和(0.94±0.08)。模型组的上述指标与空白对照组和假手术组比较,差异均有统计学意义(均P<0.05);实验组的上述指标与模型组和阴性对照组比较,差异均有统计学意义(均P<0.05)。结论SOCS3表达下调可改善更年期雌性大�Objective To investigate the effect of down-regulation of cellular signal transduction inhibitor 3(SOCS3)on leptin resistance in climacteric female rats as well as the effects on tyrosine protein kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)and phosphatidylinositol 3-kinase(PI3 K)/protein serine threonine kinase(AKT)pathway.Methods SD rats were randomly divided into blank control group,sham-operation group,model group,negative control group and experimental group.The ovariectomized operation was performed in the model group,negative control group and experimental group.Only the ovaries were separated without ligation and ova-riectomy in the sham-operation group,and no treatment was given in the blank control group.0.9%NaCl 2μL was injected into the arcuate nucleus of the hypothalamus in the blank control group,sham-operation group and model group.LV-negative 2μL was injected into the arcuate nucleus of the hypothalamus in the negative control group.LV-shSOCS32μL was injected into the arcuate nucleus of the hypothalamus in the experimental group.After 4 weeks of intervention,the content of serum leptin was measured by radioimmunoassay,the level of serum SOCS3 was detected by enzyme-linked immunosorbent assay,the expression of SOCS3 mRNA in hypothalamus was detected by reverse transcription polymerase chain reaction,the expressions of JAK2/STAT3 and PI3 K/AKT signaling pathway related proteins in hypothalamus were detected by Western blot method.Results The main indexes of experimental,model,negative control,blank control and sham-operation groups were compared:serum leptin were(1.58±0.22),(2.92±0.39),(2.88±0.34),(1.73±0.28)and(1.78±0.32)pg·mL^-1,serum SOCS3 were(94.38±8.54),(177.93±15.06),(179.08±11.43),(123.08±12.73)and(119.42±18.05)pg·mL^-1,SOCS3 mRNA were(0.39±0.15),(1.43±0.23),(1.48±0.27),(0.62±0.16)and(0.58±0.12),p-JAK2/JAK2 were(1.83±0.23),(0.48±0.16),(0.46±0.12),(1.45±0.18)and(1.51±0.27),p-STAT3/STAT3 were(1.99±0.14),(0.64±0.18),(0.59±0.23),(1.73±0.24)

关 键 词：细胞信号转导抑制因子3 瘦素抵抗 更年期 酪氨酸蛋白激酶2/信号传导子和转录激活子3 正磷脂酰肌醇3-激酶/蛋白质丝氨酸苏氨酸激酶 

分 类 号：R97[医药卫生—药品]