穿心莲内酯对糖尿病大鼠胰岛素抵抗、菌群失调及Notch/锌指蛋白转录因子1信号通路影响的研究  

Effects of andrographolide on insulin resistance,dysbiosis and Notch/Snaill signaling pathway in diabetic rats

作　　者：武莉 冯吉波 王延茹 李锦平 WU Li;FENG Jibo;WANG Yanru(Pharmacology Teaching and Research Ofice of Fenyang College,Shanri Medical University,Fenyang 032200,China)

机构地区：[1]山西医科大学汾阳学院药理教研室,汾阳032200

出　　处：《中国糖尿病杂志》2024年第7期540-545,共6页Chinese Journal of Diabetes

基　　金：山西省高等学校科技创新项目(2022L674);山西省高等学校教学改革创新项目(J20221396、J20231654);山西医科大学汾阳学院大学生创新创业训练计划项目(FDC202118);山西医科大学汾阳学院科研项目(1426)。

摘　　要：目的 探讨穿心莲内酯对DM大鼠IR、菌群失调及Notch/锌指蛋白转录因子1(Snail1)信号通路的影响。方法 选取70只SPF级Wistar雄性大鼠,其中30只进行穿心莲内酯LD50试验,确定致死量后选取50 mg/kg进行给药及观察,其余40只中10只作为空白对照组(NC),30只建立DM模型,共28只建模成功,分为T2DM组(n=9)、二甲双胍灌胃组(Met,n=9)及穿心莲内酯灌胃组(And,n=10)。NC、T2DM组不做处理,干预14 d后观察各组变化。结果 与NC组比较,T2DM、Met、And组胰岛素抵抗指数(HOMA-IR)、拟杆菌门、厚壁菌门丰度水平、Notch、Snail1 mRNA及蛋白表达、阳性表达率升高(P<0.05),乳酸杆菌、双歧杆菌丰度水平降低(P<0.05)。与T2DM组比较,Met、And组乳酸杆菌、双歧杆菌丰度水平升高(P<0.05),HOMA-IR、拟杆菌门、厚壁菌门丰度水平、Notch、Snail1 mRNA及蛋白表达、阳性表达率降低(P<0.05)。结论 DM大鼠经穿心莲内酯干预后IR缓解,菌群失调改善,Notch/Snail1信号通路受抑制。Objective To evaluate the effects of andrographolide on insulin resistance,dysbiosis and Notch/zinc finger protein transcription factor 1(Snaill)signaling pathway in diabetic rats.Methods A total of 70 male Wistar rats with SPF grade were selected,and 30 of them were selected for andrographolide LD50 test.After determining the lethal dose,50 mg/kg was selected for administration and observation,the remaining 40 rats,10 were used as the NC group,30 were established as the diabetes model,and a total of 28 rats were successfully modeled,which were divided into T2DM group(n=9),Metformin treatment group(Met,n=9),and andrographolide administration group(And,n=10).The NC group and T2DM group were not treated.The changes were evaluated after 14 days of intervention.Results Compared with NC group,HOMA-IR,the abundance levels of Bacteroidetes,Firmicute,mRNA and protein expression levels of Notch and Snaill,and positive expression rates were increased(P<0.05),while the abundance levels of Lactobacillus and Bifidobacterium were decreased in T2DM,Met and And group(P<0.05).Compared with T2DM group,HOMA-IR,the abundance levels of Bacteroidetes,Firmicute,mRNA and protein expression levels of Notch and Snaill,and positive expression rates were decreased,while the abundance levels of Lactobacillus and bifidobacterium were increased in Met and And group(P<0.05).Conclusions After andrographolide intervention,insulin resistance was alleviated,microbiota imbalance was improved,and Notch/Snaill signaling pathway was suppressed in diabetic rats.

关 键 词：穿心莲内酯 糖尿病 胰岛素抵抗 菌群失调 Notch/锌指蛋白转录因子1信号通路 

分 类 号：R285.5[医药卫生—中药学]