大黄糖络丸通过调控PI3K-Akt/NF-κB信号通路减轻糖尿病大鼠大血管炎症反应  

Rhubarb sugar pills attenuate inflammatory response in large blood vessels of diabetic rats by regulating PI3K-Akt/NF-κB signaling pathway

作　　者：姚建莉 梁永林[1] 任梦函 杨丽霞[2] YAO Jianli;LIANG Yonglin;REN Menghan;YANG Lixia(Gansu University of Traditional Chinese Medicine,Lanzhou 730000,China;Gansu Academy of Traditional Chinese Medicine,Lanzhou 730050,China)

机构地区：[1]甘肃中医药大学,甘肃兰州730000 [2]甘肃省中医药研究院,甘肃兰州730050

出　　处：《中国病理生理杂志》2024年第4期646-652,共7页Chinese Journal of Pathophysiology

基　　金：甘肃省高等学校产业支撑计划项目(No.2021CYZC-03)。

摘　　要：目的:基于磷脂酰肌醇3-激酶(PI3K)-蛋白激酶B(PKB/Akt)/核因子κB(NF-κB)信号通路,探讨大黄糖络丸(RSP)防治Zucker糖尿病肥胖(ZDF)大鼠大血管炎症反应的作用机制。方法:15只雄性ZDF(fa/+)大鼠作为对照组;高脂饲料诱导成模的75只雄性ZDF(fa/fa)大鼠随机分为模型组,高、中、低剂量RSP组,以及二甲双胍组,每组15只。药物干预12周后,处死大鼠,分离血清,检测高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)和总胆固醇(TC)水平;ELISA法检测大鼠血清CD4、白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)含量;HE染色观察大鼠腹主动脉组织病理改变;免疫组化染色检测腹主动脉中单核细胞趋化蛋白1(MCP-1)蛋白表达;RT-qPCR检测大鼠腹主动脉中PI3K、Akt和NF-κB p65的mRNA表达;Western blot观察腹主动脉组织中PI3K、Akt、p-Akt、p-IκB和NF-κB p65蛋白水平。结果:与模型组相比,RSP显著降低糖尿病大鼠空腹血糖及LDL-C、TG和TC水平(P<0.05),升高HDL-C水平(P<0.05或P<0.01),显著降低血清炎症介质表达,IL-6、TNF-α和CD4水平显著下降(P<0.05或P<0.01),腹主动脉组织病理学损伤程度显著减轻,腹主动脉中PI3K、Akt和NF-κB p65的mRNA及蛋白水平,以及MCP-1、p-Akt和p-IκB蛋白水平均显著降低(P<0.05或P<0.01)。结论:RSP可降糖调脂并减轻糖尿病大鼠大血管炎症损伤,其机制可能与抑制PI3K-Akt/NF-κB信号通路活化、减轻炎症反应有关。AIM:To explore the mechanism of rhubarb sugar pills(RSP)in preventing and treating inflammatory response in large blood vessels of Zucker diabetic fatty(ZDF)rats based on phosphatidylinositol 3-kinase(PI3K)-protein kinase B(PKB/Akt)/nuclear factor-κB(NF-κB)signaling pathway.METHODS:Fifteen male ZDF(fa/+)rats were used as the control group,and 75 male ZDF(fa/fa)rats fed with high-fat diet were randomly divided into model group,high-,medium-and low-dose RSP groups,and metformin group,with 15 rats in each group.After 12 weeks of drug intervention,the rats were euthanized,and the serum levels of high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),triglyceride(TG)and total cholesterol(TC)were measured.The serum levels of CD4,interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were detected by ELISA.The pathological changes of abdominal aorta tissue was observed by HE staining.Immunohistochemistry was conducted to assess the expression of monocyte chemoattractant protein-1(MCP-1)in the abdominal aorta.The mRNA expression of PI3K,Akt and NF-κB p65 in the abdominal aorta was measured by RT-qPCR.Western blot was utilized to observe the protein levels of PI3K,Akt,p-Akt,p-IκB and NF-κB p65 in the abdominal aorta.RESULTS:Compared with model group,RSP significantly reduced fasting blood glucose,LDL-C,TG and TC levels in diabetic rats(P<0.05),and elevated HDL-C levels(P<0.05 or P<0.01).Treatment with RSP also significantly decreased the expression of inflammatory mediators in the serum of diabetic rats,with significant decreases in IL-6,TNF-αand CD4 levels(P<0.05 or P<0.01).The pathological damage in the abdominal aorta tissue was significantly reduced,and the mRNA and protein levels of PI3K,Akt and NF-κB p65,as well as MCP-1,p-Akt and p-IκB protein levels,were all significantly decreased after RSP intervention(P<0.05 or P<0.01).CONCLUSION:Treatment with RSP can lower blood sugar and regulate lipids,thereby alleviating inflammatory damage in large blood vessels of diabetic rats.The

关 键 词：大黄糖络丸 糖尿病大血管病变 ZDF大鼠 炎症 PI3K-Akt/NF-κB信号通路 

分 类 号：R363.2[医药卫生—病理学] R587.2[医药卫生—基础医学] R285