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电针对中枢Stat 5敲除所致胰岛素抵抗小鼠肝脏胰岛素信号通路的影响 被引量:6

Hepatic IRβ/IRS 1/Akt Signaling May Contribute to the Effectiveness of Electroacupuncture in Improving Insulin Resistance in Central Stat 5 Knockout Mice
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摘要 目的:观察电针对中枢信号传导和转录活化蛋白5条件性基因敲除(Stat 5NKO)小鼠肝脏胰岛素信号通路的影响,分析电针改善胰岛素抵抗的机制。方法:将24只造模成功的雄性Stat 5NKO小鼠随机分为模型组和电针组,每组12只;12只雄性Stat 5 fl/fl小鼠作为正常组。电针组选取单侧"后三里""内庭"进行针刺治疗,2Hz/15Hz,0.8~1.0mA,20min/次,每日1次,双侧交替进行,6d为1个疗程,共治疗4个疗程。分别检测空腹血糖(FPG)、空腹胰岛素(FINS)的含量,计算胰岛素敏感指数(ISI)。运用Western blot法检测肝脏胰岛素信号通路相关蛋白胰岛素受体底物1(IRS 1)、胰岛素受体β(IRβ)、蛋白激酶B(Akt)的磷酸化表达水平。结果:与正常组小鼠相比,模型组小鼠胰岛素耐受和葡萄糖耐受功能受损(P<0.05,P<0.001),FPG明显升高、ISI下降(P<0.01);与模型组小鼠相比,电针组小鼠胰岛素耐受和葡萄糖耐受均明显增强(P<0.001,P<0.01),FPG降低、ISI升高(P<0.05);各组FINS比较差异无统计学意义(P>0.05)。与正常组小鼠相比,模型组小鼠磷酸化的IRS 1、IRβ蛋白表达显著上升(P<0.001),磷酸化的Akt蛋白表达明显下降(P<0.01);与模型组小鼠相比,电针组小鼠磷酸化的IRS 1、IRβ蛋白表达明显下降(P<0.001,P<0.01),磷酸化的Akt蛋白表达上升(P<0.01)。结论:电针通过增强肝脏Akt信号通路的传导,从而改善中枢Stat 5敲除所引起的胰岛素抵抗。 Objective To observe the effect of electroacupuncture(EA)on insulin signaling pathway in liver tissues of central neuronal specific signal transduction and activator of transcription 5 conditional-knockout(Stat 5 NKO)mice,so as to explore its mechanism underlying improvement of insulin resistance(IR).Methods Twenty-four male Stat 5 NKO mice were randomly divided into model and EA groups(n=12 mice/group),and 12 Stat 5 fl/fl mice were used as the normal control group.EA(2 Hz/15 Hz,0.8-1.0 Ma)was alternatively applied to ipsilateral"Zusanli"(ST 36)and"Neiting"(ST 44)for 20 min,once a day,6 times a week for 4 weeks.The glucose tolerance test(GTT)and insulin tolerance test(ITT)were performed,and the values of fasting plasma glucose(FPG)and fasting insulin(FINS)were measured by glucometer and ELISA,separately.The insulin sensitivity index(ISI)was calculated.The phosphorylation protein expressions of insulin receptor substrate 1(IRS 1),insulin receptorβ(Irβ)and protein kinases B(Akt)in the liver tissues were detected by Western blot.Results In Stat 5 NKO mice(model group),FPG level and glucose area under the curve(GAUC)of ITT and GTT were significantly increased(P〈0.01,P〈0.05,P〈0.001),while the ISI was notably down-regulated in comparison with the Stat 5 fl/fl mice(normal group,P〈0.01),suggesting an impairment of both glucose tolerance(GT)and insulin tolerance(IT)in mice of the model group.After the EA treatment,the increased FPG and GAUC levels and the decreased ISI were reversed markedly(P〈0.05,P〈0.01,P〈0.001).No significant differences were found in FINS among the three groups(P〈0.05).Compared with the normal group,the protein expression levels of liver p-IRS 1 and p-Irβwere significantly up-regulated(P〈0.001),and the p-Akt expression was significantly down-regulated(P〈0.01)in the model group.Following EA treatment,the increased p-IRS 1 and p-Irβprotein expression and the decreased p-Akt
作者 李敏慧 洪浩 卢圣锋 王军蒙 朱冰梅 LI Min-hui,HONG Hao,LU Sheng-feng,WANG Jun-meng,ZHU Bing-mei(Key Laboratory for Researching Combination of Acupuncture and Chinese Materia Medica of Ministry of Education, Nanjing University of Traditional Chinese Medicine, Nanjing 210023, Chin)
出处 《针刺研究》 CAS CSCD 北大核心 2018年第5期314-318,共5页 Acupuncture Research
基金 国家自然科学基金面上项目(No.81574063) 江苏省研究生培养创新工程项目(No.KYZZ 16-0411) 江苏省高校自然科学研究面上项目(No.17KJB 360006)
关键词 电针 胰岛素抵抗 胰岛素受体底物1 胰岛素受体β 蛋白激酶B Electroacupuncture Insulin resistance Insulin receptor substrate 1 Insulin receptor β Protein kinases B
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