miR-22靶向NLRP3基因对冠心病大鼠内皮细胞炎症损伤的影响研究

Effect of microRNA-22targeting NLRP3gene on endothelial cell inflammation in rats with coronary heart disease

目的研究miR-22靶向NLRP3基因对冠心病大鼠内皮细胞炎症损伤的影响。方法选取22只健康SD大鼠进行研究,随机分成研究组和对照组,对照组大鼠不进行特殊处理,研究组构建大鼠动脉粥样硬化(AS)模型,对比两组大鼠血钙和血脂水平、大鼠心肌组织的miR-22和NLRP3、caspase-1mRNA表达水平,以及心肌组织NLRP3、caspase-1蛋白表达水平;在经过细胞转染分组后,分成空白组(未转染)、阴性组、miR-22mimic组、miR-22inhibitor组和miR-22inhibitor+si NLRP3组,对比几组的miR-22和NLRP3、caspase-1mRNA表达水平,NLRP3、caspase-1蛋白表达水平,以及炎症因子表达水平。结果研究组的TC、TG、LDLC和Ca2+水平均明显高于对照组(P<0.05);研究组的miR-22水平明显低于对照组,NLRP3、caspase-1mRNA表达水平以及NLRP3、caspase-1蛋白表达水平均明显高于对照组(P<0.05);miR-22mimic组的miR-22明显高于空白组,NLRP3、caspase-1mRNA表达显著低于空白组(P<0.05),miR-22inhibitor组和空白组的对比结果与之相反(P<0.05);miR-22mimic组的NLRP3、caspase-1蛋白表达均明显低于空白组(P<0.05),miR-22inhibitor组明显高于空白组(P<0.05);miR-22mimic组的IL-1β、IL-6和IL-18水平明显低于空白组和阴性组,IL-10明显高于空白组与阴性组(P<0.05),miR-22inhibitor组与空白组及阴性组的炎症因子水平对比结果与之相反(P<0.05)。结论 miR-22能够利用显著的NLRP3基因靶向抑制效果,改善冠心病大鼠的内皮细胞凋亡状况,且能够促进炎症因子水平的下降,具有显著的内皮细胞保护作用。

Objective To study the effect of miR-22 targeting NLRP3 gene on inflammatory injury of endothelial cells in rats with coronary heart disease(CAD).Methods 22 healthy SD rats were randomly divided into study group and control group.The rats in the control group were not treated with special treatment.The atherosclerotic(AS)model was established in the study group,and the levels of blood calcium and blood lipid in the two groups were compared.The expression of miR-22 and NLRP3,caspase-1 mRNA in rat myocardium and the expression of NLRP3,caspase-1 protein in myocardial tissue were also studied.After being divided into two groups,the cells were divided into two groups.The levels of miR-22 and NLRP3,caspase-1 mRNA expression levels,NLRP3,caspase-1 protein expression levels,and inflammatory factor expression levels were compared in the blank group(not transfected),the negative group,the miR-22 mimic group,the miR-22 inhibitor group,and the miR-22 inhibitor+si NLRP3 group.Results The levels of TC,TG,LDLC and Ca2+in the study group were significantly higher than that in the control group(P<0.05).The level of miR-22 in the study group was significantly lower than that of the control group(P<0.05).Compared with the control group(P<0.05),the expression level of NLRP3,caspase-1 mRNA and the expression level of NLRP3 and caspase-1 were significantly higher than that in the control group(P<0.05).The expression of the miR-22 in the miR-22 mimic group was significantly lower than that of the blank group(P<0.05),and the results of the comparison between the miR-22 inhibitor group and the blank group were the opposite(P<0.05).NLRP3,caspase-1 in miR-22 mimic group.The expression of protein was significantly lower than that in the blank group(P<0.05),and the miR-22-inhibitor group was significantly higher than that in the blank group(P<0.05).IL1β,IL6 and IL18 levels in miR-22 mimic group were significantly lower than that in blank group and negative group,IL10 was significantly higher than that in blank group and negative group(P<0.05).Conclusion miR 22 can target inhibition of NLRP3 gene.The invention has the effects of improving the apoptosis of the endothelial cells in the coronary heart disease rat,and can promote the reduction of the level of the inflammatory factors,and has a remarkable protective effect on the endothelial cells.