温阳活血解毒方调控RIPK1/NLRP3/Caspase-1稳定动脉粥样硬化易损斑块的作用研究  

Decoction for warming Yang and removing toxin stabilizes atherosclerotic vulnerable plaquevia regulating NLRP3/Caspase-1 pathway

作　　者：陈卓铭 刘小灵 黄娜 郑国煜 余锋[1] 洪永敦[1] 刘南[1] CHEN Zhuoming;LIU Xiaoling;HUANG Na;ZHENG Guoyu;YU Feng;HONG Yongdun;LIU Nan(First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong,China;Foshan Hospital of Traditional Chinese Medicine,Foshan 528000,Guangdong,China)

机构地区：[1]广州中医药大学第一附属医院,广东广州510405 [2]佛山市中医院,广东佛山528000

出　　处：《现代中西医结合杂志》2024年第22期3067-3072,3087,共7页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：广州市科技计划项目(202201020323)。

摘　　要：目的探讨温阳活血解方对动脉粥样硬化大鼠斑块稳定性及主动脉组织中受体相互作用蛋白激酶1(RIPK1)、含NLR家族Pyr in域蛋白3(NLRP3)、半胱氨酸蛋白水解酶1(Caspase-1)表达的影响。方法取40只健康成年Wistar大鼠,采用高脂饲料喂养联合维生素D 3腹腔注射方法建立动脉粥样硬化模型。将造模成功的35只大鼠随机分为模型组、辛伐他汀组及温阳活血解毒方低、中、高剂量组,每组7只。继续高脂饲料喂养12周,在此期间温阳活血解毒方低、中、高剂量组分别给予11.55 g/(kg·d)、23.10 g/(kg·d)、46.20 g/(kg·d)温阳活血解毒方灌胃,辛伐他汀组给予浓度2 mg/mL的辛伐他汀药液2.10 mg/(kg·d)灌胃,模型组给予蒸馏水0.2 mL/10 g灌胃,均1次/d。末次灌胃结束后第2天,全自动生化仪检测血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平,HE染色观察主动脉组织病理形态,Western blot法检测主动脉组织中磷酸化RIPK1(p-RIPK1)、RIPK1、NLRP3、Caspase-1蛋白表达情况。结果温阳活血解毒方低剂量组大鼠血清TC、TG、LDL-C、HDL-C水平和主动脉组织中p-RIPK1、RIPK1、NLRP3、Caspase-1蛋白相对表达量与模型组比较差异均无统计学意义(P均>0.05),且主动脉组织结构差异不大,斑块整体稳定性差;温阳活血解毒方中、高剂量组和辛伐他汀组大鼠血清TC、TG、LDL-C水平和主动脉组织中p-RIPK1、RIPK1、NLRP3、Caspase-1蛋白相对表达量均明显低于模型组(P均<0.05),血清HDL-C水平均明显高于模型组(P均<0.05),斑块整体稳定好于模型组;温阳活血解毒方中、高剂量组和辛伐他汀组间血清TC、TG、LDL-C、HDL-C水平和主动脉组织中NLRP3、Caspase-1蛋白相对表达量比较差异均无统计学意义(P均>0.05);温阳活血解毒方高剂量组和辛伐他汀组p-RIPK1、RIPK1蛋白相对表达量均明显低于温阳活血解毒方中剂量组(P均<0.05);温阳�Objective It is to explore the effects of decoction for warming Yang and removing toxin on blood lipids,plaque stability and expressions of receptor-interacting protein kinase 1(RIPK1),NLR-family Pyrin domain-containing protein 3(NLRP3),and Caspase-1 in aortic tissues in atherosclerotic rats.Methods Forty healthy adult Wistar rats were fed with high-fat diet and intraperitoneally injected with vitamin D 3 to establish models of atherosclerosis.35 successfully modeled rats were randomly divided into model group,simvastatin group,and the low,medium,and high dose groups of decoction for warming Yang and removing toxin,with 7 rats in each group.The rats were continued to fed with high-fat diet for 12 weeks,during which the low,medium,and high dose groups of decoction for warming Yang and removing toxin were given decoction for warming Yang and removing toxin 11.55 g/(kg·d),23.10 g/(kg·d),and 46.20 g/(kg·d)by gavage,respectively,while the simvastatin group was administered with 2 mg/mL simvastatin solution 2.10 mg/(kg·d)by gavage,and the model group was administered with distilled water 0.2mL/10g by gavage,all once daily.On the second day after the last gavage,the serum levels of triacylglycerol(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were measured by automatic biochemistry,the pathological morphology of aortic tissues was observed by HE staining,and the protein expressions of phosphorylated RIPK1(p-RIPK1),RIPK1,NLRP3,and Caspase-1 in aortic tissues were detected by Western blot.Results The differences in serum levels of TC,TG,LDL-C,HDL-C and relative protein expressions of p-RIPK1,RIPK1,NLRP3,Caspase-1 in aortic tissues of rats were not significant between the low dose group of decoction for warming Yang and removing toxin and model group(all P>0.05),and there was little difference in the aortic tissue structure,and the overall stability of the plaque was poor.The serum levels of TC,TG,LDL-C and relative protein expressions of p-RIPK1,RIP

关 键 词：动脉粥样硬化 温阳活血解毒 NLRP3 CASPASE-1 

分 类 号：R-332[医药卫生]