电针调控PI3K/Nrf2/HO-1通路对T2DM大鼠肾脏保护作用的研究  

Protective Effect of EA on Kidneys of Rats with T2DM by Regulating PI3K/Nrf2/HO-1 Signaling Pathway

作　　者：魏倩文 李瑞 段浩茹 刘邵阳 庄舒婷 郭卫星 董滢 宋姗姗 徐梦琪 WEI Qianwen;LI Rui;DUAN Haoru;LIU Shaoyang;ZHUANG Shuting;GUO Weixing;DONG Ying;SONG Shanshan;XU Mengqi(School of Acupuncture-Moxibustion and Tuina,Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学针灸推拿学院,北京100029

出　　处：《针灸临床杂志》2024年第6期78-84,共7页Journal of Clinical Acupuncture and Moxibustion

基　　金：国家自然科学基金面上项目,编号:81973935。

摘　　要：目的:观察电针对糖尿病大鼠肾脏磷脂酰肌醇3激酶(PI3K)/核因子E2相关因子2(Nrf2)/血红素氧合酶-1(HO-1)通路的影响,探讨其对肾脏的保护机制。方法:将18只雄性Wistar大鼠随机分为空白组、模型组和电针组,每组6只。本研究采用2%链脲佐菌素溶液(35 mg/kg)注射于腹腔并饲以高糖高脂饲料构建2型糖尿病大鼠模型。电针组取双侧“胃脘下俞”“脾俞”“足三里”“三阴交”干预,于同侧“足三里”“胃脘下俞”给予电针刺激,1次/d,连续6周。于造模前、电针前后测量空腹血糖(FBG);酶比色法检测血清丙二醛(MDA)和超氧化物歧化酶(SOD)及尿素(UREA)含量;荧光免疫法检测血清活性氧(ROS)含量;HE染色观察肾脏形态学变化;蛋白免疫印迹法检测肾脏PI3K、蛋白激酶B(Akt)、Nrf2和HO-1蛋白表达情况。结果:干预前,与空白组比较,模型组、电针组大鼠FBG均升高,差异具有统计学意义(P<0.01)。干预6周后,与空白组比较,模型组大鼠血清FBG、MDA、ROS及UREA水平均显著升高,差异具有统计学意义(P<0.01),血清SOD含量、肾脏PI3K、Akt、Nrf2及HO-1蛋白表达均显著降低,差异具有统计学意义(P<0.01);与模型组比较,电针组大鼠血清FBG、MDA、ROS及UREA水平均显著降低,差异具有统计学意义(P<0.01);血清SOD含量、肾脏PI3K、Akt、Nrf2及HO-1蛋白表达均显著升高,差异具有统计学意义(P<0.01)。HE染色显示模型组较空白组病理改变明显,电针组整体情况优于模型组。结论:电针可明显降低2型糖尿病大鼠氧化应激水平并缓解大鼠肾脏内部形态的病理性改变,对肾脏的保护机制或与激活PI3K/Nrf2/HO-1通路相关。Objective:To observe the effect of electro-acupuncture(EA) on PI3K/Nrf2/HO-1 signaling pathway in rats with type 2 diabetes mellitus(T2DM),thus to explore the mechanism of EA on protecting kidneys of T2DM rats.Methods:18 male Wistar rats were randomly divided into the blank group,the model group and the EA group,with 6 rats in each group.The T2DM model was established by intraperitoneal injection of 2% streptozotocin solution(35 mg/kg) combined with high-sugar and high-fat diet feeding.The EA group was intervened with bilateral needling Weiwanxiashu(EX-B3),Pishu(BL20),Zusanli(ST36) and Sanyinjiao(SP6),with electro-acupuncture stimulation applying to ST36 and EX-B3,once a day for 6 weeks consecutively.FBG was recorded before modeling,as well as before and after EA.The serum levels of MDA,SOD and UREA were detected by enzyme colorimetric method.The serum level of ROS was measured by immunofluorescence method.The morphological changes of kidneys were observed by HE staining.The protein expressions of PI3K,Akt,Nrf2 and HO-1 were evaluated by Western Blot.Results:Before the intervention,FBG was higher in the model group and the EA group compared with that in the blank group(P<0.01).After 6 weeks of intervention,the levels of FBG,MDA,ROS and UREA were significantly increased(P<0.01),and the serum level of SOD and protein expressions of PI3K,Akt,Nrf2 and HO-1 were significantly decreased in the model group compared with those in the blank group(P<0.01).Compared with those in the model group,the levels of FBG,MDA,ROS and UREA were significantly decreased(P<0.01),the serum level of SOD and the protein expressions of PI3K,Akt,Nrf2 and HO-1 were significantly increased in the EA group(P<0.01).HE staining showed that the pathological changes of the model group were more obvious than those of the blank group,and the overall condition of the EA group was better than that of the model group.Conclusion:EA can significantly reduce oxidative stress level in the rats with T2DM and alleviate the internal pathological changes of kidn

关 键 词：2型糖尿病 电针 氧化应激 磷脂酰肌醇3激酶 核因子E2相关因子2 血红素氧合酶-1 

分 类 号：R246.1[医药卫生—针灸推拿学]