电针对胰岛素抵抗大鼠下丘脑磷脂酰肌醇3激酶及磷脂酰肌醇3激酶催化亚基蛋白表达的影响

目的:观察"双固一通"电针法对胰岛素抵抗模型大鼠下丘脑中的磷脂酰肌醇3激酶(PI 3Kp 110)及磷脂酰肌醇3激酶催化亚基(p-PI 3Kp 110)蛋白表达的影响,探讨"双固一通"电针法改善胰岛素抵抗的机制。方法:雄性Wistar大鼠随机分为正常组、模型组、预防组、电针组、脑脊液组及阻滞剂组,每组10只。以高脂饮食喂养复制胰岛素抵抗模型大鼠。预防组、电针组、脑脊液组和阻滞剂组电针"关元""后三里""丰隆""中脘",每周治疗5次,预防组治疗16周,其余各组治疗8周。脑脊液组进行脑室内人工脑脊液灌注,阻滞剂组脑室内灌注渥曼青霉素。观察造模后及治疗后各组大鼠体质量(BW)、空腹血糖(FPG)、血清胰岛素(FINS)水平,并比较各组胰岛素敏感指数(IAI);Western blot法检测大鼠下丘脑PI 3Kp 110及p-PI 3Kp 110蛋白表达。结果:与正常组比较,模型组、预防组、电针组、脑脊液组及阻滞剂组造模后BW、FPG及FINS明显升高(P0.01,P0.05),IAI降低(P0.01);与模型组比较,治疗后预防组与电针组大鼠BW、FPG、FINS降低(P0.05,P0.01),脑脊液组BW、FPG降低(P0.05,P0.01),预防组、电针组及脑脊液组IAI升高(P0.05);与阻滞剂组比较,脑脊液组、电针组及预防组BW、FPG、FINS降低(P0.05,P0.01),IAI升高(P0.05)。与正常组比较,模型组下丘脑PI 3Kp 110及pPI 3Kp 110蛋白表达减少(P0.01);与模型组比较,预防组、电针组、脑脊液组PI 3Kp 110及p-PI 3Kp 110蛋白表达升高(P0.01,P0.05);与阻滞剂组比较,预防组、电针组、脑脊液组PI 3Kp 110及pPI 3Kp 110蛋白表达升高(P0.01,P0.05)。结论:"双固一通"电针法改善胰岛素抵抗状态,与提高模型大鼠下丘脑中PI 3Kp 110蛋白及p-PI 3Kp 110蛋白表达有关。

Effects of Electroacupuncture Intervention on Expression of Hypothalamic PI 3Kand p-PI 3K Proteins in Insulin Resistance Model Rats

Objective To observe the effect of"Shuanggu Yitong"(Double-reinforcing and one-unblocking)needlingelectroacupuncture(EA)of"Guanyuan"(CV 4),"Housanli"(ST 36),"Fenglong"(ST 40)and"Zhongwan"(CV 12)]on expression of hypothalamic phosphatidylinositol 3-kinase(PI 3K)and p-PI 3Kproteins in insulin resistance rats.Methods Sixty Wistar rats were randomized into normal control,model,EA prevention,EA,cerebrospinal fluid(CSF),and Wortmannin(PI 3K antagonist)groups(n=10rats/group).Insulin resistance model was established by feeding the animal with high fat forage continuously for 8weeks.For rats of the EA group,EA(2Hz,1mA)was applied to ipsilateral"Housanli"(ST 36)-"Fenglong"(ST40),and"Guanyuan"(CV 4)-"Zhongwan"(CV 12)for 15min,once daily,5times a week and for 8weeks,beginning after modeling.For rats of the EA prevention group,EA was conducted simultaneously with the modeling.For rats of the Wortmannin group and CSF group,cerebroventricular microinjection of Wortmannin(50nmol/L,3mg/kg)or artificial CSF was given through an implanted steel cannel.Fasting plasma glucose(FPG)and fasting serum insulin(FINS)contents were assayed using glucosetested instrument and ELISA respectively,insulin activity index(IAI)was calculatedIAI=Ln(1/FPG×FINS)],and the expression of hypothalamic PI 3Kand p-PI 3Kproteins was detected by Western blot.Results In comparison with the normal control group,the body weight(BW),FPG and FINS contents at time-points of 8and 16weeks were considerably increased(P<0.01),and IAI,hypothalamic PI 3Kp 110and p-PI 3Kp 110protein expression levels were obviously decreased in the model group(P<0.01).Compared with the model group,the FPG and FINS contents at the 8th week after modeling in the EA prevention group,the BW and FPG levels at the 16th week in the EA prevention,EA and CSF groups,FINS levels at the 16th week in the EA prevention and EA groups were remarkably decreased(P<0.05,P<0.01),IAI,and hypothalamic PI 3Kp 110 and pPI 3Kp 110protein expression levels were significantly up-regulated in the EA prevention,EA and CSF groups(P<0.05,P<0.01).No significant differences were found among the EA prevention,EA and CSF groups,and between the model and Wortmannin groups in the BW,FPG,FINS,IAI and hypothalamic PI 3Kp 110and p-PI 3Kp 110expression levels(P>0.05).Conclusion EA intervention can reduce insulin resistance by suppressing the increase of body weight,blood glucose and insulin contents,and increasing hypothalamic PI 3Kexpression levels in insulin resistance rats.