摘要
目的:分析雷公藤甲素对肺动脉高压大鼠免疫炎症的影响及其作用机制,为临床上肺动脉高压患者的治疗提供参考。方法:选取90只雄性大鼠,15只作为正常组,其余作为肺动脉高压组,皮下注射野百合碱(MCT)建立肺动脉高压模型,建模成功后肺动脉高压组分为模型组、阳性对照组、雷公藤甲素A组、雷公藤甲素B组、雷公藤甲素C组5个亚组。阳性对照组使用30 mg/kg泼生坦灌胃,雷公藤甲素A、B、C组分别腹腔注射0.1、0.2、0.4 mg/kg雷公藤甲素,正常组、模型组注射等体积生理盐水。连续干预28 d后,对比各组mPAP、RVSP,右心室肥厚指数(RVHI)、肺小动脉形态、肺小动脉重塑、免疫炎症相关指标及Toll样受体4/核因子κB(TLR4/NF-κB)信号通路蛋白表达量。结果:①模型组、阳性对照组、雷公藤甲素A、B、C组mPAP、RVSP、RVHI、MT%、MA%、Th17细胞比例、IL-6、IL-17水平、TLR4、NF-κB表达量均高于正常组,Treg细胞比例、IL-10水平低于正常组(P<0.05)。②阳性对照组、雷公藤甲素A、B、C组mPAP、RVSP、RVHI、MT%、MA%、Th17细胞比例、IL-6、IL-17水平、TLR4、NF-κB表达量低于模型组,Treg细胞比例、IL-10水平高于模型组(P<0.05)。③雷公藤甲素A、B、C组mPAP、RVSP、RVHI、MT%、MA%、Th17细胞比例、IL-6、IL-17水平、TLR4、NF-κB表达量均低于阳性对照组,Treg细胞比例、IL-10水平高于阳性对照组(P<0.05)。④随着雷公藤甲素干预剂量增加,mPAP、RVSP、RVHI、MT%、MA%、Th17细胞比例、IL-6、IL-17水平、TLR4、NF-κB表达量逐渐降低,Treg细胞比例、IL-10水平逐渐升高(P<0.05)。结论:雷公藤甲素可修复肺动脉高压累及的心脏损伤,抑制肺小动脉重塑,分析其作用机制可能与抑制TLR4/NF-κB信号通路所介导的免疫反应有关,且上述作用呈剂量依赖性,高剂量雷公藤甲素作用更为明显。
Objective:To analyze the effect of triptolide on the immune inflammation of pulmonary hypertension rats and its mechanism of action,and provide reference for the clinical treatment of pulmonary hypertension.Methods:Selected 90 male rats,in which 15 as the normal group,and the rest as the pulmonary hypertension group.MCT was injected subcutaneously to establish the pulmonary hypertension model.After successful modeling,the pulmonary hypertension components were model group,positive control group,triptolide A group,triptolide B group and triptolide C group.The positive control group received 30 mg/kg of Presentan by ga-vage,triptolide A,B and C groups were intraperitoneally injected with 0.1,0.2,0.4 mg/kg of triptolide,respectively,the normal group and the model group were injected with the same volume of saline.After 28 days of continuous intervention,compare each groups of mPAP,RVSP,right ventricular hypertrophy index(RVHI),pulmonary vascular morphology,pulmonary vascular remodel-ing,immune inflammation-related indicators,and Toll-like receptor 4/nuclear factorκB(TLR4/NF-κB)amount of protein expression in the signaling pathway.Results:①Model group,positive control group,triptolide A,B,C groups mPAP,RVSP,RVHI,MT%,MA%,Th17 cell ratio,IL-6,IL-17 level,TLR4,NF-κB expressions were higher than the normal group,and the ratio of Treg cells and IL-10 level were lower than those in normal group(P<0.05).②The positive control group,triptolide A,B,C groups mPAP,RVSP,RVHI,MT%,MA%,Th17 cell ratio,IL-6,IL-17 levels,TLR4,NF-κB expressions were lower than the model group,the proportion of Treg cells and the level of IL-10 were higher than those in the model group(P<0.05).③Triptolide A,B,C groups mPAP,RVSP,RVHI,MT%,MA%,Th17 cell ratio,IL-6,IL-17 levels,TLR4,and NF-κB expressions were all lower than those in positive control group.The proportion of Treg cells and the level of IL-10 were higher than those of the positive control group(P<0.05).④With the increase of the intervention dose of triptolide,mPAP,RVSP,RVHI,MT%,MA%,Th17 cell ratio,IL-6,IL-17 levels,TLR4,NF-κB expression levels gradually decreased,and the proportion of Treg cells and IL-10 levels gradually increased(P<0.05).Conclusion:Triptolide can repair the heart damage involved in pulmonary hypertension and inhibit the remodeling of pulmonary arteri-oles.The analysis of its mechanism may be related to the suppression of the immune response mediated by the TLR4/NF-κB signaling pathway,and the above effects are dose-dependent.The effect of high-dose triptolide is more obvious.
作者
王梅爱
黄秋虹
陈慧勤
黄倩
郑丹丹
WANG Meiai;HUANG Qiuhong;CHEN Huiqin;HUANG Qian;ZHENG Dandan(Department of Basic Medicine,Quanzhou Medical College,Quanzhou 362000,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2024年第2期343-347,354,共6页
Chinese Journal of Immunology
基金
泉州市科学技术局项目(2021N127S)。
关键词
雷公藤甲素
肺动脉高压
免疫炎症
肺小动脉重塑
Triptolide
Pulmonary hypertension
Immune inflammation
Pulmonary arteriole remodeling
