基于PI3K/Akt信号通路探讨富硒灵芝对妊娠期糖尿病大鼠的保护机制  

Protective Effects of Se-enriched Ganoderma on Rats with Gestational Diabetes Mellitus Based on PI3K/Akt Signaling Pathway

作　　者：李顺序 何飞敏 华蕾 张思成 王永梅 LI Shunxu;HE Feimin;HUA Lei;ZHANG Sicheng;WANG Yongmei(The Third People′s Hospital of Yunnan Province,Kunming 650011,China;Kunming Hospital Affiliated to Dali University)

机构地区：[1]云南省第三人民医院,云南昆明650011 [2]大理大学附属昆明医院

出　　处：《西部中医药》2022年第12期30-34,共5页Western Journal of Traditional Chinese Medicine

基　　金：云南省科技计划重点项目(2017-1-S-16730);云南省医学重点学科建设项目(2018-2022)。

摘　　要：目的:基于PI3K/Akt信号通路探讨富硒灵芝对妊娠期糖尿病(gestational diabetes mellitus,GDM)大鼠的保护作用机制。方法:选择12只雌性大鼠为正常组,68只雌性大鼠构建GDM模型大鼠,选择造模成功60只大鼠分为模型组,二甲双胍治疗组,富硒灵芝低、中、高剂量组,每组12只,各组给予相应干预14天。检测大鼠血清空腹血糖(fasting blood glucose,FBG)、空腹胰岛素(fasting insulin,FINS),并计算HOMA-IR(hom ostasis model assessment-insulin resistance,HOMA-IR)。采集肝脏组织观察病理学改变,并检测肝脏炎性因子白细胞介素1α(interleukin-1α,IL-1α)、白细胞介素6(interleukin-6,IL-6)及肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、氧化应激指标超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽(glutathione,GSH)和丙二醛(malonaldehyde,MDA)含量。采用免疫印迹法检测肝脏磷脂酰肌醇3激酶(phosphatidylinositol-3-kinase,PI3K)、p-PI3K、蛋白激酶B(protein kinase B,Akt)、p-Akt蛋白表达特点。结果:与正常组相比,模型组FBG和HOMA-IR均明显升高(P<0.05),FINS水平明显降低(P<0.05);与模型组相比,二甲双胍和富硒灵芝治疗后均有一定的改善(P<0.05)。与正常组相比,模型组肝脏炎性因子IL-1α、IL-6、TNF-α和MDA水平均明显升高(P<0.05),SOD和GSH均明显降低(P<0.05);与模型组相比,富硒灵芝各剂量组及二甲双胍组IL-1α、IL-6、TNF-α和MDA水平均明显降低(P<0.05),SOD和GSH明显升高(P<0.05)。组织病理学正常组肝脏细胞结构清晰完整,模型组则出现明显损伤,与模型组相比,各治疗组均有明显好转。与正常组比较,模型组肝脏p-PI3K和p-Akt蛋白显著降低(P<0.05);与模型组比较,富硒灵芝各剂量与二甲双胍组胰岛组织p-PI3K和p-Akt蛋白显著升高(P<0.05);而PI3K和Akt蛋白各组间无明显统计学差异(P>0.05)。结论:富硒灵芝能够降低妊娠期糖尿病大鼠炎症反应,增加胰岛素敏感性,提高抗氧化能力,其作用机制�Objective:To survey the mechanism of Se-enriched ganoderma protecting GDM rats based on PI3K/Akt signaling pathway.Methods:Twelve female rats were chosen as the normal group,68 female rats were prepared into GDM models,60 successfully modeling rats were selected and allocated to the model group,the treatment group of melbine,low,moderate and high doses groups of Se-enriched ganoderma,12 rats in each group,different groups accepted the corresponding intervention for 14 days.To detect the levels of FBG and FINS in rats,and calculate HOMA-IR.Liver was collected to observe pathological changes,to detect liver inflammatory factors including the contents of IL-1α,IL-6 and TNF-α,together with oxidative stress indexes containing SOD,GSH and MDA,Western Blotting was adopted to detect the expressions of PI3K,p-PI3K,Akt and p-Akt protein in the liver.Results:Compared with the normal group,the levels of FBG and HOMA-IR were increased apparently in the model group(P<0.05);the levels of FINS were noticeably decreased(P<0.05);compared with the model group,the symptoms were improved after treating by melbine and Se-enriched ganoderma(P<0.05).Compared with the normal group,the levels of IL-1α,IL-6,TNF-αand MDA were obviously raised in the model group(P<0.05),the contents of SOD and GSH were noticeably decreased(P<0.05);compared with the model group,the levels of IL-1α,IL-6,TNF-αand MDA were remarkably reduced in different doses groups of Se-enriched ganoderma and the treatment group of melbine(P<0.05),the contents of SOD and GSH were obviously raised(P<0.05).Histopathological results showed that the structure of liver cells in the normal group was clear and intact,while the cells of the model group showed obvious damage,compared with the model group,different therapy groups were improved clearly.Compared with the normal group,the expressions of liver p-PI3K and p-Akt protein were remarkably decreased in the model group(P<0.05);compared with the model group,the expressions of liver pPI3K and p-Akt protein were significantly

关 键 词：糖尿病 妊娠期 富硒灵芝 大鼠 磷脂酰肌醇激/蛋白激酶 B信号通路 

分 类 号：R587.1[医药卫生—内分泌]