PM2.5暴露对大鼠心脏功能及NLRP3炎性小体表达的影响  

Effects of PM2. 5 exposure on cardiac functions and the NLRP3 inflammasome in rats and its mechanism

作　　者：张行行 赵麓 孙欠欠 赵安东 周甜雨 王川[1,2] 刘继平 王斌[1,2] ZHANG Hanghang;ZHAO Lu;SUN Qianqian;ZHAO Andong;ZHOU Tianyu;WANG Chuan;LIU Jiping;WANG Bin(Shaanxi University of Chinese Medicine,Xianyang 712046;China.2.Key Laboratory of Pharmacodynamic Mechanism and Material Basis of Traditional Chinese Medicine,Shaanxi Provincial Administration of Traditional Chinese Medicine,Xianyang 712046)

机构地区：[1]陕西中医药大学,陕西咸阳712046 [2]陕西省中医药管理局中药药效机制与物质基础重点研究室,陕西咸阳712046

出　　处：《中国实验动物学报》2023年第4期445-453,共9页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科技基金项目(81473385);陕西中医药大学学科创新项目(2019-YL13)。

摘　　要：目的 探究气道吸入不同浓度PM2.5混悬液是否能激活大鼠心肌组织NLRP3炎性小体引起心脏功能的损伤,为寻找相关药物干预提供参考。方法 SD大鼠随机分为对照组,低(7.5 mg/kg)、中(15 mg/kg)、高(30 mg/kg)剂量染毒组,每组7只。染毒组通过非暴露式气管滴注相应剂量混悬液(1 mL/kg),6 d 1次,持续2个月,对照组大鼠滴注等量生理盐水,滴注期间每日记录大鼠生理状况。末次滴注完成后,禁食12 h, 1%戊巴比妥钠(50 mg/kg)麻醉,以心肌组织病理切片、心肌细胞凋亡状况、心肌谱酶变化反应心脏功能状况;以心肌组织Bcl-2,Bax蛋白;NLRP3、Caspase-1、IL-1β蛋白及mRNA表达,血清中IL-1β、IL-6、TNF-α、IL-18表达水平反应心肌组织NLRP3炎性小体的活化状况。结果 滴注不同剂量PM2.5混悬液后,各染毒组大鼠不同程度毛色变黄、无光泽,活动减少,饮食、体重无明显影响,心肌组织出现不同程度的横纹断裂、细胞减少、排列无规则、细胞核固缩、水肿的现象。与对照组相比,染毒组大鼠心肌组织中CK、LDH、AST水平,Bcl-2、IL-1β蛋白表达、NLRP3、IL-1β、Caspase-1 mRNA表达,血清中IL-1β、IL-6、IL-18、TNF-α水平均显著升高,Bax蛋白表达、Bcl-2/Bax值显著降低;中剂量组和高剂量组大鼠心肌细胞凋亡显著增加,NLRP3、Caspase-1蛋白表达显著升高;低剂量组大鼠心肌组织细胞凋亡,NLRP3、Caspase-1蛋白表达与对照组无显著性差异。结论 PM2.5暴露可造成心肌细胞结构损伤、激活NLRP3炎性小体,促进炎性因子和凋亡蛋白表达,引起心肌组织功能的损伤。Objective To investigate whether airway inhalation of a PM2.5 suspension at carious concentrations activates the NLRP3 inflammasome in rat myocardial tissue to induce cardiac damage and provide a reference to research drug treatments.Methods SD rats were randomly divided into a control group(Sham)and low(Low,7.5 mg/kg),middle(Middle,15 mg/kg),and high(High,30 mg/kg)exposure groups with seven in each group.The exposure groups were instilled with the corresponding dose of suspension(1 mL/kg)through a non-exposed trachea once every 6 days for 2 months,and rats in the Sham group were instilled with the same amount of normal saline.Physiological status was recorded daily.After the last infusion,the rats were fasted for 12 hours and then anesthetized with 1%sodium pentobarbital(50 mg/kg).The cardiac function status was reflected by pathological sections of myocardial tissue,myocardial cell apoptosis,and changes in myocardial enzymes.Bcl-2 and Bax protein expression,and NLRP3,Caspase-1,and IL-1βprotein and mRNA expression in myocardial tissue,and serum IL-1β,IL-6,TNF-α,and IL-18 levels reflected the NLRP3 inflammasome activation status in myocardial tissue.Results After instillation of various doses of PM2.5 suspension,the rats in exposure groups became yellow,dull,and had decreased activity to varying degrees.There was no significant effect on diet or body weight.Decreased,irregular arrangement,nuclear pyknosis,edema.Compared with the Sham group,CK,LDH,and AST levels in myocardial tissue,Bcl-2 and IL-1βprotein expression,NLRP3,IL-1β,and Caspase-1 mRNA expression,serum of IL-1βand IL-6.IL-18 and TNF-αlevels were significantly increased,Bax protein expression,and the Bcl-2/Bax ratio were decreased significantly.Cardiomyocyte apoptosis in Middle and High groups was significantly increased,and NLRP3 and Caspase-1 protein expression was significantly increased.Significantly increased;myocardial tissue apoptosis in the Low group and NLRP3 and Caspase-1 protein expression were not significantly different from those in

关 键 词：PM2.5 NLRP3 心肌损伤 气管滴注 细胞凋亡 

分 类 号：Q95-33[生物学—动物学]