文章摘要
电针调控PI3K/Nrf2/HO-1通路对T2DM大鼠肾脏保护作用的研究
The protective effect of electroacupuncture regulating on PI3K/Nrf2/HO-1 signaling pathway in the kidney of rats with type 2 diabetes mellitus
投稿时间:2024-02-26  录用日期:2024-04-12
DOI:
中文关键词: 电针  2型糖尿病  氧化应激  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)
英文关键词: Electro-acupuncture  Type 2 diabetes mellitus  oxidative stress  phosphatidylinositol-3 kinase (PI3K)  nuclear factor erythroid 2-related factor 2(Nrf2)  heme oxygenase-1 (HO-1)
基金项目:国家自然科学基金项目(面上项目,重点项目,重大项目)
作者单位邮编
魏倩文 北京中医药大学 10029
李瑞* 北京中医药大学 10029
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中文摘要:
      目的:观察电针对糖尿病大鼠肾脏磷脂酰肌醇3激酶(phosphatidylinositol-3 kinase, PI3K)/核因子E2相关因子2(nuclear factor erythroid 2-related factor 2, Nrf2)/血红素氧合酶-1(heme oxygenase-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,电针组,每组6只。本研究采用高糖高脂饲料喂养结合1% 链脲佐菌素溶液(35 mg/kg)腹腔注射构建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”给与电针刺激,每日1次,连续6周。于造模前、电针前后测量空腹血糖(fasting blood glucose, FBG);酶比色法检测血清尿素(Urea)含量、超氧化物歧化酶(superoxide dismutase, SOD)活性和丙二醛(malondialdehyde, MDA)含量;荧光免疫法检测血清活性氧(reactive oxygen species, 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(protein kinase B, Akt)和Nrf2、HO-1蛋白表达水平。结果:干预前,与空白组相比,模型组、电针组大鼠血清FBG均显著升高(P<0.01)。干预6周后,与空白组相比,模型组大鼠血清FBG,Urea、ROS、MDA水平均显著升高(P<0.01),血清SOD活性、肾脏PI3K、Akt、Nrf2及HO-1蛋白表达均显著降低(P<0.01);与模型组相比,电针组大鼠血清FBG、Urea、ROS、 MDA水平均显著降低(P<0.01);血清SOD活性、肾脏PI3K、Akt、Nrf2、HO-1蛋白表达均显著升高(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,其对肾脏的保护机制或与激活PI3K/Nrf2/HO-1通路相关。
英文摘要:
      Objective: To observe the effect of electro-acupuncture (EA) on kidney protein phosphatidylinositide 3-kinases(PI3K)/nuclear factor erythroid2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway in rats with type 2 diabetes mellitus(T2DM), and to explore the mechanism of EA on protecting kidney of T2DM rats. Methods: 18 male Wistar rats were randomly divided into blank group, model group, EA group, with 6 rats in each group. Rats in model group and EA group were fed with high-sugar and high-fat diets combined with intraperitoneal injection of 1% streptozotocin (STZ) solution (35 mg/kg) to establish T2DM rat model in this research. The EA group was treated with needling bilateral Weiwanxiashu (EX-B3), Pishu (BL20), Zusanli (ST36) and Sanyinjiao (SP6), and among which EX-B3 and ST36 on one side had EA applied, once a day, for 6 weeks consecutively. The fasting blood glucose (FBG) in each group was compared before modeling, before intervention and after intervention. Serum levels of Urea and the expression of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by enzyme colorimetric method, serum level of reactive oxygen species (ROS) was detected by immunofluorescence method. HE staining was used to observe the morphological changes of the kidney of the rats in each group. Western Blot method was applied to detect the protein expressions of PI3K、protein kinase B (Akt) and Nrf2、HO-1 in the kidney of the rats in each group. Results: Before the intervention, compared with those in the blank group, the value of FBG was significantly higher in the model group and the EA group(P<0.01). After 6 weeks of intervention, compared with those in the blank group, the value of FBG and serum levels of Urea、ROS and MDA were significantly increased(P<0.01), the serum level of SOD and protein expression of PI3K、Akt、Nrf2、HO-1 were significantly decreased(P<0.01); compared with those in the model group, the value of FBG and serum levels of Urea、ROS and MDA were significantly decreased(P<0.01), the serum level of SOD and protein expression of PI3K、Akt、Nrf2、HO-1 were significantly increased(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 kidney in rats. The mechanism of protecting kidney may be related to activating PI3K/Nrf2/HO-1 signaling pathway.
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