电针对胰岛素抵抗肥胖大鼠下丘脑胰岛素敏感性及TLR4/IκBα/NF-κB信号通路的影响

Wu Huan, Chen Li, Zhang Zhao-Qing, Chen Bang-Guo, Liang Feng-Xia, Lin Wei

Department of Rehabilitation, Wuhan Third Hospital, Wuhan 430065, China.

College of Acupuncture-moxibustion and Orthopedics, Hubei University of Chinese Medicine, Wuhan 430061.

Zhen Ci Yan Jiu. 2021 Jan 25;46(1):33-8. doi: 10.13702/j.1000-0607.200324.

OBJECTIVE

To observe the effects of electroacupuncture on the hypothalamic Toll-like receptor 4 (TLR4)/ inhibitor nuclear factor kappa-B α(IκBα)/nuclear factor-κB (NF-κB) signaling pathway in obese insulin resistance (OIR) rats，so as to explore the mechanism of EA underlying improving of insulin resistance.

METHODS

Rats were randomly divided into normal, model and EA groups, with 8 rats in each group. The rat model of OIR was established by feeding with high-fat diet for 8 weeks. EA(2 Hz，1 mA)was applied to unilateral"Zusanli"(ST36),"Fenglong"(ST40),"Zhongwan"(CV12)and"Guanyuan"(CV4)for 10 min, 3 times a week for 8 weeks. The body mass, fasting blood glucose(FBG) and postprandial blood glucose (PBG) were measured before and after 2、4、6、8 weeks' intervention. An intraperitoneal injection glucose tolerance test and hyperglycemic clamps were applied to test insulin resistance. The expression of TLR4、p-IκBα、NF-κB p65、TNF-α、IL-1β mRNA and protein in hypothalamus was detected by quantitative real-time PCR and Western blot, separately.

RESULTS

Compared with the normal group, the body mass and PBG of the model group were significantly increased (<0.01); glucose infusion rate(GIR) was significantly reduced (<0.01); in the IPGTT test, the increase in blood glucose was significantly greater after 90 and 120 min of glucose injection(<0.01); the hypothalamus TLR4, NF-κB p65，p-IκBα, TNF-α, IL-1β mRNA and protein expressions were all significantly increased (<0.01). After EA intervention, the body weight and PBG were significantly down-regulated after 6 weeks and 2 weeks of intervention (<0.05, <0.01); GIR were significantly up-regulated after 8 weeks of intervention (<0.05); In the IPGTT test, the increase in blood glucose 60 min after glucose injection was significantly down-regulated (<0.05); hypothalamus TLR4, NF-κB p65，p-IκBα, TNF-α, IL -1β mRNA and protein expression were significantly down-regulated (<0.01).

CONCLUSION

EA can reduce the body weight of OIR rats and improve IR, which may be related to down-regulating the hypothalamic TLR4/IκBα/NF-κB signaling pathway.

目的

观察电针对肥胖胰岛素抵抗（OIR）大鼠下丘脑Toll样受体4（TLR4）/抑制因子核因子κBα（IκBα）/核因子κB（NF-κB）信号通路的影响，以探讨电针改善胰岛素抵抗的机制。

方法

将大鼠随机分为正常组、模型组和电针组，每组8只。采用高脂饮食喂养8周建立OIR大鼠模型。电针（2Hz，1mA）刺激单侧“足三里”（ST36）、“丰隆”（ST40）、“中脘”（CV12）和“关元”（CV4），每次10分钟，每周3次，共8周。在干预2、4、6、8周前后分别测量体重、空腹血糖（FBG）和餐后血糖（PBG）。采用腹腔注射葡萄糖耐量试验和高血糖钳夹技术检测胰岛素抵抗。分别采用定量实时PCR和蛋白质印迹法检测下丘脑TLR4、p-IκBα、NF-κB p65、TNF-α、IL-1βmRNA和蛋白的表达。

结果

与正常组相比，模型组体重和PBG显著升高（<0.01）；葡萄糖输注速率（GIR）显著降低（<0.01）；在腹腔注射葡萄糖耐量试验中，注射葡萄糖90和120分钟后血糖升高幅度显著增大（<0.01）；下丘脑TLR4、NF-κB p65、p-IκBα、TNF-α、IL-1βmRNA和蛋白表达均显著升高（<0.01）。电针干预后，干预6周和2周后体重和PBG显著下调（<0.05，<0.01）；干预8周后GIR显著上调（<0.05）；在腹腔注射葡萄糖耐量试验中，注射葡萄糖60分钟后血糖升高幅度显著下调（<0.05）；下丘脑TLR4、NF-κB p65、p-IκBα、TNF-α、IL-1βmRNA和蛋白表达显著下调（<0.01）。