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南京中医药大学针药结合教育部重点实验室
纸质出版日期:2018
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李敏慧, 洪浩, 卢圣锋, 等. 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[J]. 针刺研究, 2018,43(5):314-318.
LI Min-hui, HONG Hao, LU Sheng-feng, et al. Hepatic IRβ/IRS 1/Akt Signaling May Contribute to the Effectiveness of Electroacupuncture in Improving Insulin Resistance in Central Stat 5 Knockout Mice[J]. Acupuncture research, 2018, 43(5): 314-318.
李敏慧, 洪浩, 卢圣锋, 等. 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[J]. 针刺研究, 2018,43(5):314-318. DOI: 10.13702/j.1000-0607.170803.
LI Min-hui, HONG Hao, LU Sheng-feng, et al. Hepatic IRβ/IRS 1/Akt Signaling May Contribute to the Effectiveness of Electroacupuncture in Improving Insulin Resistance in Central Stat 5 Knockout Mice[J]. Acupuncture research, 2018, 43(5): 314-318. DOI: 10.13702/j.1000-0607.170803.
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 expression were apparently reversed in the EA group relevant to the model group(P<0.001
P<0.01).Conclusion EA can improve the IR induced by central neuronal Stat 5-knockout in mice
which may contribute to its effectiveness in regulating hepatic IRβ/IRS 1/Akt signaling pathway.
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