摘要
为探讨芪苈参萸益心方对心肌梗死(MI)大鼠炎症反应、溶酶体功能和NLRP3炎症小体的影响及机制。将实验大鼠随机分为正常组、模型组、芪苈参萸益心方组和地尔硫卓组。MI模型复制成功后分别予芪苈参萸益心方及地尔硫卓处理,正常组、模型组予0.5%羧甲基纤维素钠溶液,连续4周,处死大鼠,观察血流动力学,血液中ROS、LDH、SOD、GSH-Px、CAT、MDA、TNF-α、IL-1β、IL-6、IL-18、IL-4、IL-10及血液、心肌和溶酶体中β-葡萄糖醛酸酶、β-半乳糖苷酶、组织蛋白酶B和D、心脏重量指数、心肌梗死面积的变化;HE染色观察心脏形态学改变;实时定量PCR测定心肌中TLR4、MyD88、iNOS、COX-2 mRNA表达,Western blot测定心肌中p-IKKβ、p-IκBα、NLRP3、ASC、pro-caspase-1、caspase-1、TXNIP、pro-IL-1β、pro-IL-18及胞浆和胞核中NF-κBp65蛋白表达。结果显示芪苈参萸益心方可显著改善MI大鼠心功能、降低心脏重量指数和梗死面积,减少心肌坏死和炎性细胞浸润;降低血液LDH、ROS、MDA、TNF-α、IL-1β、IL-6、IL-18及血液、心肌和溶酶体中β-葡萄糖醛酸酶、β-半乳糖苷酶、组织蛋白酶B和D水平;升高血液中SOD、CAT、GSH-Px、IL-4、IL-10水平;下调心肌中TLR4、MyD88、iNOS、COX-2 mRNA及p-IKKβ、p-IκBα、NLRP3、ASC、pro-caspase-1、caspase-1、TXNIP、pro-IL-1β、pro-IL-18、胞核NF-κBp65蛋白表达及p-IKKβ/IKKβ和p-IκBα/IκBα比值,上调胞浆中NF-κBp65蛋白表达(P<0.05或P<0.01)。芪苈参萸益心方对MI大鼠有保护作用,其机制可能与增强内源性抗氧化系统功能、减轻炎症反应和抑制NLRP3炎症小体激活有关。
To observe the effect of Qili Shenyu Yixin Formula on the inflammatory reaction,lysosomal function and NLRP3 inflammasome in myocardial infarction(MI)rats.The rats were randomly divided into normal group,model group,Qili Shenyu Yixin Formula groups and diltiazem group.After the successful replication of MI model,Qili Shenyu Yixin Formula and diltiazem were given respectively.The normal and model groups were given 0.5%sodium carboxymethyl cellulose solution.After 4 weeks,the hemodynamics,blood ROS,LDH,SOD,GSH-Px,CAT,MDA,TNF-α,IL-1β,IL-6,IL-18,IL-4,IL-10,blood,myocardium and lysosomeβ-glucuronidase,β-galactosidase,cathepsin B and D cardiac mass index and myocardial infarction volume,myocardium and lysosome were observed;HE staining were used to observe cardiac morphological changes;The real-time PCR was applied to detect the mRNA expressions of TLR4,MyD88 and iNOS in myocardial tissue;The protein expressions of p-IKKβ,p-IκBα,NLRP3,ASC,pro-caspase-1,caspase-1,TXNIP,pro-IL-1β,pro-IL-18 and cytosol and nucleus NF-κBp65 in myocardial tissue were detected by Western blot.The results indicated that Qili Shenyu Yixin Formula could significantly improve cardiac function,reduce cardiac mass index and infarct area,reduce myocardial necrosis and inflammatory cell infiltration,decrease blood LDH,ROS,MDA,TNF-α,IL-1β,IL-6,IL-18 and blood,myocardium and lysosomeβ-glucuronidase,β-galactosidase,cathepsin B and D levels;elevate blood SOD,CAT,GSH-Px,IL-4 and IL-10 levels;down-regulate the TLR4,MyD88,iNOS,COX-2 mRNA expressions,p-IKKβ,p-IκBα,NLRP3,ASC,pro-caspase-1,caspase-1,TXNIP,pro-IL-1β,pro-IL-18,nuclear NF-κBp65 protein expressions and p-IKKβ/IKKβand p-IκBα/IκBαratios;up-regulate the cytosol NF-κBp65 protein expression of in the myocardial tissue(P<0.05 or P<0.01,respectively).Qilishenyu Yixin Formula has protective effect on MI rats,which is possibly related to enhancing endogenous antioxidant system function,reducing inflammatory reaction and inhibiting inflammasome activation.
作者
卢超
石孟琼
张媛媛
罗恒
陈腊年
任俊红
舒恒
张继红
LU Chao;SHI Meng-qiong;ZHANG Yuan-yuan;LUO Heng;CHEN La-nian;REN Jun-hong;SHU Heng;ZHANG Ji-hong(The Second People's Hospital,China Three Gorges University & Yichang Second Hospital;Medical Science College;Hubei Key Laboratory of Natural Products Research and Development & College of Biological and Pharmaceutical Sciences,China Three Gorges University,Yichang 443002,China)
出处
《天然产物研究与开发》
CAS
CSCD
北大核心
2020年第11期1833-1843,1832,共12页
Natural Product Research and Development
基金
湖北省卫生厅项目(2012Z-Y07)
湖北省宜昌市科技局项目(A16-301-30)。
关键词
芪苈参萸益心方
心肌梗死
炎症反应
溶酶体功能
NLRP3炎症小体激活
Qili Shenyu Yixin Formula
myocardial infarction
inflammatory reaction
lysosomal function
activation of NLRP3 inflammasome
