针刺研究

2021, v.46(11) 901-906+947

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电针“足三里”对糖尿病大鼠胰腺及海马中tau蛋白磷酸化水平的影响
Electroacupuncture at “Zusanli”(ST36) ameliorates tau hyperphosphorylation in pancreas and hippocampus of diabetic rats

袁芳;洪小平;段妍君;陈姣蓉;韩永明;
YUAN Fang;HONG Xiao-ping;DUAN Yan-jun;CHEN Jiao-rong;HAN Yong-ming;College of Basic Medicine, Hubei University of Chinese Medicine;

摘要(Abstract):

目的:观察电针"足三里"对2型糖尿病(T2DM)大鼠胰腺及海马中磷酸化tau蛋白水平的影响,探讨电针防治糖尿病痴呆的作用机制。方法:SD雄性大鼠随机分为对照组、模型组和电针组,每组16只。高脂高糖饮食6周联合腹腔注射链脲佐菌素(35 mg/kg)制备T2DM大鼠模型。造模成功1周后电针组大鼠予电针"足三里",每次30 min,每日1次,每周6次,连续干预4周。记录大鼠生存率,并测定大鼠空腹血糖(FBG),酶联免疫吸附法检测大鼠血清胰岛素水平;HE染色法观察各组大鼠胰岛形态结构;免疫组织化学法检测胰腺和海马中丝氨酸396位点磷酸化的tau蛋白(pS396)、苏氨酸231位点磷酸化的tau蛋白(pT231)的表达;Western blot法检测胰腺和海马中pS396、pT231、总tau蛋白(Tau5)、磷酸化糖原合酶-3β(pGSK-3β)、总糖原合酶-3β(GSK-3β)的表达量。结果:与对照组比较,模型组大鼠在造模成功后4周生存率呈现明显的下降趋势;模型组大鼠的FBG及胰岛素水平均显著升高(P<0.01),胰岛明显缩小,结构紊乱,界限不清;胰腺和海马pS396、pT231表达水平显著增高(P<0.01),pGSK表达水平显著降低(P<0.01)。与模型组比较,电针组大鼠在造模成功后的生存率升高;FBG及胰岛素水平均明显降低(P<0.05),胰岛面积增大,细胞排列较规则,边界相对清晰;胰腺和海马pS396、pT231表达水平明显降低(P<0.05,P<0.01),pGSK-3β水平显著升高(P<0.01)。结论:电针"足三里"可能通过调控胰腺及海马内GSK-3β信号分子活性,降低大鼠海马内磷酸化tau蛋白的表达水平,从而有效保护糖尿病大鼠大脑的功能。
Objective To observe the effect of electroacupuncture(EA) at “Zusanli”(ST36) on the phosphorylated tau levels in pancreas and hippocampus of type 2 diabetes mellitus(T2 DM) rats, so as to explore the underlying mechanism of EA in diabetic demention rats. Methods Forty-eight male Sprague-Dawley rats were randomly divided into control, model and EA groups, with 16 rats in each group. The T2 DM model was established by 6 weeks of high-fat, high-sugar diet as well as intrape-ritoneal injection of streptozocin(STZ) solution(35 mg/kg). After that, EA(2 Hz, 0.1 mA) was applied to unilateral “Zusanli”(ST36) for 30 min, once a day, 6 times a week for 4 weeks. The survival rate was recorded every week, and the fasting blood glucose(FBG) was detected on the 1~(st), 6~(th) and 11~(th) week. The level of serum insulin(INS) was measured by using ELISA. The morphological structure of pancreas islet was observed by H.E. staining. The expressions of phosphorylated tau at the sites of Ser 396(pS396) and Thr 231(pT231), total tau(Tau5), phosphorylated glycogen synthase kinase-3β(pGSK-3β) and total glycogen synthase kinase-3β(GSK-3β) in pancreas and hippocampus were detected by Western blot. The expression and distribution of pS396 and pT231 in pancreas and hippocampus were assayed with immunohistochemistry.Results Compared with the control group, the survival rate presented a significant decline, the contents of FBG and INS were obviously higher(P<0.01), and the structure of the pancreas islet appeared shrunken, obscure and disordered in the model group. Furthermore, the levels of pS396, pT231 in pancreas and hippocampus were obviously higher in the model group(P<0.01),while the level of pGSK-3β in pancreas and hippocampus was significantly lower in the model group(P<0.01). In comparison with the model group, the survival rate of EA group was higher. Following 4 weeks' interventions, the enhanced levels of tau phosphorylation and GSK-3β activity in pancreas and hippocampus were partly reversed in the EA group compared to the model group(P<0.05,P<0.01). Conclusion EA at ST36 can reduce the level of tau phosphorylation via regulating the activity of GSK-3β in the pancreas and hippocampus of T2 DM rats, which may be related with the effect of EA on the brain function in T2 DM rats.

关键词(KeyWords): 电针;糖尿病;胰腺;海马;tau蛋白磷酸化
Electroacupuncture;Diabetes;Pancreas;Hippocampus;Tau phosphorylation

Abstract:

Keywords:

基金项目(Foundation): 湖北省自然科学基金项目(No.2018CFB697)

作者(Author): 袁芳;洪小平;段妍君;陈姣蓉;韩永明;
YUAN Fang;HONG Xiao-ping;DUAN Yan-jun;CHEN Jiao-rong;HAN Yong-ming;College of Basic Medicine, Hubei University of Chinese Medicine;

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DOI: 10.13702/j.1000-0607.200921

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