首页|吴茱萸碱调节cGAS-STING信号通路对妊娠糖尿病大鼠炎症反应的影响

吴茱萸碱调节cGAS-STING信号通路对妊娠糖尿病大鼠炎症反应的影响

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目的 探讨吴茱萸碱(EVO)调节环状GMP-AMP合成酶cGAS-干扰素基因刺激因子(STING)信号通路对妊娠糖尿病(GDM)大鼠炎症反应的影响.方法 随机选出10只大鼠作为对照组(NC组),其余大鼠构建GDM大鼠模型,造模成功后随机平分为 GDM组、EVO 组(10 mg/kg)、SR-717 组(cGAS-STING信号通路激活剂 3 mg/kg)、EVO+SR-717 组(10 mg/kgEVO+3 mg/kg SR-717),每组均10只,给药每天1次,持续2周.血糖仪检查大鼠FBG水平;全自动生化分析仪检测血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)的含量;ELISA法检测肾组织炎性因子以及氧化应激水平;HE染色检测肾组织病理变化;Western blot检测cGAS-STING/通路蛋白表达.结果 NC组大鼠肾组织染色清晰,结构正常;GDM组肾小管排列杂乱,肾小球基底膜增厚,肾小球肿胀,炎性细胞浸润.与NC组相比,GDM组胎盘、胎鼠重量、空腹血糖(FBG)、TC、TG、LDL水平、肿瘤坏死因子-α(TNF-α)、白细胞介素1β(IL-1β)含量、超氧化物歧化酶(SOD)含量、cGAS、STING蛋白水平显著升高(P<0.05),SOD、谷胱甘肽(GSH)含量显著下降(P<0.05);EVO组较GDM组肾结构明显改善,胎盘、胎鼠重量、FBG、TC、TG、LDL水平、TNF-α、IL-1β含量、MDA含量、cGAS、STING蛋白水平显著减少(P<0.05),SOD、GSH含量显著增加(P<0.05);而SR-717组加重肾小球肿胀以及炎性细胞浸润现象,以上指标与EVO组趋势相反;SR-717逆转了EVO对GDM大鼠的有利影响.结论 EVO可能通过下调cGAS-STING信号通路发挥减轻GDM大鼠炎症反应的作用.
Impact of evodiamine on inflammatory response in rats with gestational diabetes mellitus by regulating cGAS-STING signal pathway
Objective The study investigates the impact of evodiamine(EVO)on inflammatory response in rats with gesta-tional diabetes mellitus by regulating cGAS-STING signaling pathway.Methods Ten rats were randomly selected as a control group(NC group),and the remaining rats were constructed into a GDM rat mode.After successful modeling,they were randomly grouped in-to GDM group,EVO group(10 mg/kg),SR-717 group(cGAS-STING signal pathway activator 3 mg/kg),and EVO+SR-717 group(10 mg/kg EVO+3 mg/kg SR-717),with 10 rats in each group.They were administered once a day for 2 weeks.Blood glucose meter was applied to check the FBG level of the rats;The fully automatic biochemical analyzer detects the contents of serum total cholesterol(TC),triglyceride(TG),and low-density lipoprotein(LDL).ELISA method was used to detect inflammatory factors and oxidative stress levels in renal tissue.HE staining was applied to detect the pathological changes of renal tissue;Western blot was applied to detect the expression of cGAS-STING pathway protein.Results In NC group,the renal tissue was stained clearly and the structure was nor-mal;in GDM group,renal tubules were disorderly arranged,with glo-merular basement membrane thickened,glomerular swelling,and in-flammatory cell infiltration.Compared with NC group,the placenta weight,fetal rat weight,FBG,TC,TG,LDL levels,TNF-α and IL-1βcontents,MDA content,cGAS and STING protein levels in GDM group increased significantly(P<0.05),while the SOD and GSH con-tents decreased significantly(P<0.05).Compared with GDM group,the renal structure of the EVO group was significantly improved,and the placenta weight,fetal rat weight,FBG,TC,TG,LDL levels,TNF-α and IL-1β contents,MDA content,cGAS and STING pro-tein levels in EVO group reduced significantly(P<0.05),while the SOD and GSH contents increased significantly(P<0.05).In the SR-717 group,glomerular swelling and inflammatory cell infiltration were aggravated,and the above indicators showed the opposite trend to the EVO group.SR-717 reversed the beneficial effects of EVO on GDM rats.Conclusion EVO may play a role in reducing inflammatory response in GDM rats by down-regulating the cGAS-STING signaling pathway.

evodiamineCGAS-STING signal pathwaygestational diabetes mellitusinflammatory reaction

李振、王毅、韩森吉、孙静、邵利军、刘东芳

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255200 淄博,淄博市第一医院产科

吴茱萸碱 cGAS-STING信号通路 妊娠糖尿病 炎症反应

2024

医学研究生学报
南京军区南京总医院

医学研究生学报

CSTPCD北大核心
影响因子:1.652
ISSN:1008-8199
年,卷(期):2024.37(9)