PM2.5诱导血管内皮细胞凋亡在老年冠心病中的作用机制

Mechanism of PM2.5 induced apoptosis of vascular endothelial cells in elderly patients with coronary heart disease

中文关键词: 老年  大气中细颗粒物  冠心病  血管内皮细胞  细胞凋亡  氧化应激

英文关键词: elderly  PM2.5  coronary heart disease  vascular endothelial cell  cell apoptosis  oxidative stress

中文摘要:

      目的 分析老年冠心病患者的心功能分级与本市大气中细颗粒物(PM2.5)含量的相关性,并通过体外培养血管内皮细胞,探讨PM2.5是否会导致血管内皮细胞凋亡,并进一步探讨炎症和氧化应激在其中的可能作用和机制.方法 本研究分为两部分,第一部分为临床研究,回顾性收集安徽中医药高等专科学校附属芜湖市中医院2021 年1 月—2022 年9月诊断为冠心病的103 例老年患者,按照冠心病的心功能分级将其分为1～4 级,分析老年冠心病患者的心功能分级与本市大气中PM2.5含量的变化趋势.首先按照冠心病的心功能分级,在心功能＜3 级和心功能≥3 级 2 组病例中,分别比较PM2.5浓度、血压、糖尿病史、糖化血红蛋白和住院史的差异;其次按照PM2.5 浓度分组,在PM2.5＜75 μg/m3 和PM2.5≥75 μg/m3 2 组人群中,分别比较老年冠心病患者的心功能分级、血压、糖尿病史、糖化血红蛋白及住院史的差异.第二部分则通过培养人脐静脉内皮细胞(HUVECs),予以不同浓度梯度的PM2.5干预HUVECs细胞48h后,Tunel染色检测细胞凋亡情况,荧光显微镜观察ROS的表达与分布,ELISA方法检测SOD活力,RT-PCR方法检测细胞中炎症因子IL-6 的mRNA表达.结果 第一部分研究结果显示老年冠心病患者的心功能分级与本地区空气中 PM2.5 的浓度变化趋势一致,且心功能＜3 级和心功能≥3 级2 组人群所暴露的大气PM2.5 浓度差异有统计学意义(P＜0.05).第二部分研究结果显示不同浓度的PM2.5可诱导HUVECs细胞凋亡;PM2.5呈浓度依赖性地诱导HUVECs细胞中ROS表达和分布增多;并抑制HUVECs细胞的SOD活性(P＜0.05);不同浓度PM2.5可诱导HUVECs细胞的炎症因子IL-6 mRNA表达量明显上调(P＜0.05).结论 老年冠心病的心功能严重程度与大气中的PM2.5 含量高低有关;PM2.5 可导致血管内皮细胞凋亡,同时刺激炎症因子表达和氧化应激水平的增加,这可能是其参与老年患者冠心病进展的重要机制之一.

英文摘要:

      Objective To analyze the correlation between the cardiac function grading of elderly patients with coronary heart disease(CHD)and the concentration of fine particulate matter(PM2.5)in the atmosphere of this city,explore whether PM2.5 can induce apoptosis of vascular endothelial cells by cultured vascular endothelial cells in vitro,and further explore the possible roles and mechanisms of inflammation and oxidative stress in it.Methods This study included two parts.In the first part,103 elderly patients diagnosed with CHD in Wuhu Hospital of Traditional Chinese Medicine Affiliated to Anhui College of Traditional Chinese Medicine from January 2021 to September 2022 were retrospectively collected.According to their heart function grading,they were divided into 1～4 grading.The heart function grading of elderly CHD patients and the trend of change in PM2.5 concentration in the city's atmosphere were analyzed.First,the differences in PM2.5 concentration,blood pres-sure,diabetes history,glycosylated hemoglobin and hospitalization history were compared between the two groups of patients with＜3 grading and≥3 grading of heart function according to the cardiac function grading.Secondly,the differences in cardi-ac function grading,blood pressure,diabetes history,glycosylated hemoglobin and hospitalization history were compared be-tween the PM2.5＜75 μg/m3 group and PM2.5≥75 μg/m3 group according to PM2.5 concentration,respectively.In the second part,human umbilical vein endothelial cells(HUVECs)were cultured.After 48 hours of intervention with different concentra-tion gradients of PM2.5 on HUVECs,Tunel staining was used to detect cell apoptosis,fluorescence microscopy was used to ob-serve the expression and distribution of ROS,ELISA method was used to detect SOD activity,and RT-PCR method was used to detect the mRNA expression of inflammatory factor IL-6 in the cells.Results The results of the first part of this study showed that the cardiac function grading of elderly CHD patients was consistent with the trend of changes in PM2.5 concentration in the air of the local area.There was no statistically significant difference(P＞0.05)in the exposure of atmospheric PM2.5 concen-trationbetweenthetwogroupswithheartfunction＜3 grading and heart function≥3 grading(P＜0.05).The results of the second part of this study showed that different concentrations of PM2.5 could induce apoptosis of HUVECs.PM2.5 induced the increase of ROS expression and distribution in HUVECs in a concentration-dependent manner,and inhibited SOD activity in HUVECs(P＜0.05).Different concentrations of PM2.5 could significantly up-regulate the mRNA expression of inflammatory factor IL-6 in HUVECs(P＜0.05).Conclusion The severity of CHD in the elderly is related to PM2.5 concentration in the atmosphere.PM2.5 can induce apoptosis of vascular endothelial cells,and stimulate the expression of inflammatory factors and increase the level of oxidative stress,which may be one of the important mechanisms involved in the progression of CHD in eld-erly patients.