文献类型：期刊文献

中文题名：大黄糖络丸调控NLRP3/Caspase-1/GSDMD通路改善糖尿病大鼠大血管炎症损伤的作用机制

英文题名：Mechanism of Rhubarb Tangluo Pills Regulating NLRP3/Caspase-1/GSDMD Pathway to Ameliorate Inflammatory Injury in Large Vessels of Diabetic Rats

作者：闫丰喆[1];白敏[1];杨丽霞[2];宋冰[1];张延英[1];郭超[1];梁永林[1];朱向东[3]

第一作者：闫丰喆

机构：[1]甘肃中医药大学,兰州730000;[2]绍兴市人民医院,浙江绍兴312035;[3]宁夏医科大学,银川750004

第一机构：甘肃中医药大学

年份：2025

卷号：42

期号：15

起止页码：2580

中文期刊名：中国现代应用药学

外文期刊名：Chinese Journal of Modern Applied Pharmacy

收录：;北大核心:【北大核心2023】；

基金：甘肃省科技计划项目(23JRRA1218);甘肃省教育科技创新项目(2021CYZC-03);甘肃省药品科研项目(2022GSMPA001)。

语种：中文

中文关键词：糖尿病大血管病变;大黄糖络丸;炎症损伤;NLRP3/Caspase-1/GSDMD通路

外文关键词：diabetic macroangiopathy;Rhubarb Tangluo pills;inflammatory injury;NLRP3/Caspase-1/GSDMD pathway

摘要：目的明确大黄糖络丸对糖尿病大鼠大血管损伤的干预作用,并基于NLRP3/Caspase-1/GSDMD通路介导炎症损伤探讨其具体机制。方法选取40只SPF级9周龄ZDF(纯合子fa/fa)大鼠进行实验,适应性喂养1周后采用Purina#5008饲料诱导3周复制糖尿病大鼠模型,成模后随机分为模型对照组、二甲双胍组(0.18g·kg^(-1))和大黄糖络丸高、中、低剂量组(2.16、1.08、0.54 g·kg^(-1)),另选8只同龄ZDF(杂合子fa/+)大鼠作为空白对照组,干预12周后测定大鼠体质量和空腹血糖。采用全自动生化分析仪检测血浆中TC、TG、LDL-c、HDL-c的含量;采用HE染色法观察大鼠血管组织病理形态变化;采用ELISA技术检测血清中IL-1β和IL-18的含量;采用Westernblotting与RT-qPCR技术检测血管组织中NLRP3、ASC、Caspase-1、GSDMD蛋白和mRNA表达水平。结果与空白对照组相比,模型对照组大鼠体质量和空腹血糖含量显著升高(P<0.05),TC、TG、LDL-c含量显著升高(P<0.05),HDL-c含量显著降低(P<0.05),血管内细胞排列不规则且出现细胞空泡,血管内膜增厚,IL-1β、IL-18含量显著增加(P<0.05),NLRP3、ASC、Caspase-1、GSDMD蛋白和mRNA表达显著增加(P<0.05)。与模型对照组相比,大黄糖络丸高、中量组及二甲双胍组大鼠体质量和空腹血糖均显著降低(P<0.05),TC、TG、LDL-c含量显著升高(P<0.05),HDL-c含量显著降低(P<0.05),不同程度改善了血管病理损伤,血清中炎症因子(IL-1β、IL-18)含量显著降低(P<0.05),NLRP3、ASC、Caspase-1、GSDMD的蛋白与mRNA表达显著降低(P<0.05)。与大黄糖络丸低剂量组相比,大黄糖络丸高剂量组有更加显著的改善作用(P<0.05)。结论大黄糖络丸能够显著改善糖尿病大鼠血管损伤,并呈剂量依赖性,其具体机制与大黄糖络丸抑制NLRP3/Caspase-1/GSDMD通路改善血管炎症性损伤有关。
OBJECTIVE To clarify the interventional effects of Rhubarb Tangluo pills on macrovascular injury in diabetic rats and to explore the specific mechanisms based on the NLRP3/Caspase-1/GSDMD pathway mediating inflammatory injury.METHODS Forty SPF-grade 9-week-old ZDF(purebred fa/fa)rats were selected for the experiment,and the diabetic rats model was induced by Purina#5008 chow for 3 weeks after 1 week of acclimatization feeding,and then randomly divided into model control group,metformin group(0.18 g·kg^(-1)),and high-,medium-,low-dose group of Rhubarb Tangluo pills(2.16,1.08,0.54 g·kg^(-1))after the model was formed.Another 8 ZDF(heterozygous fa/+)rats of the same age were selected as blank control group,and the body mass and fasting blood glucose of the rats were measured after 12 weeks of intervention.The plasma levels of TC,TG,LDL-c and HDL-c were detected using an automatic biochemical analyzer;the pathomorphological changes of rat vascular tissues were observed using HE staining;the serum levels of IL-1βand IL-18 were detected using ELISA;and the expression levels of NLRP3,ASC,Caspase-1 and GSDMD protein and mRNA expression level were detected by Western blotting and RT-qPCR techniques.2580·Chin J Mod Appl Pharm,2025 August,Vol.42,No.15 RESULTS Compared with the blank control group,rats in the model control group showed significantly higher body mass and fasting glucose content(P<0.05),significantly higher TC,TG,LDL-c content(P<0.05),significantly lower HDL-c content(P<0.05),irregular cell arrangement and cell vacuoles in the vasculature,thickening of vascular endothelium,and significant increase in the content of IL-1β,IL-18(P<0.05),increased expression of NLRP3,ASC,Caspase-1,GSDMD protein and mRNA(P<0.05).Compared with the model control group,body mass and fasting blood glucose of rats in the high-and medium-dose group of Rhubarb Tangluo pills and the metformin group were significantly reduced(P<0.05),TC,TG,LDL-c content was significantly increased(P<0.05),HDL-c content was significantly reduced(P<0.05),vascular pathological injury was improved to different degrees,and the content of serum inflammatory factors(IL-1β,IL-18)was significantly reduced(P<0.05),protein and mRNA expression of NLRP3,ASC,Caspase-1,GSDMD were significantly reduced(P<0.05).Compared with the low-dose group,the high-dose group of Rhubarb Tangluo pills showed more significant improvement(P<0.05).CONCLUSION Rhubarb Tangluo pills can significantly improve vascular injury in diabetic rats in a dose-dependent manner,and the specific mechanism is related to the inhibition of NLRP3/Caspase-1/GSDMD pathway by Rhubarb Tangluo pills to improve vascular inflammatory injury.