NLRP NLRP3炎性小体及丹参通脉方治疗冠状动脉粥样硬化性心脏病临床研究

Clinical Study of NLRP3 inflammasome and Danshen Tongmai Formula in the Treatment of Coronary Heart Disease

目的探讨寡聚化结构域样受体蛋白3(NLRP3)炎性小体及丹参通脉方治疗冠状动脉粥样硬化性心脏病(简称冠心病)的临床疗效,以及对患者白细胞介素(IL)-1β、IL-18、转化生长因子-β(TGF-β)水平的影响。方法选取医院2021年2月至2022年2月收治的冠心病患者100例(研究组),以及同期来医院进行健康体检者100名(常规组)。采用定量逆转录聚合酶链反应(RT-qPCR)、免疫印迹(Western blot)法分别检测外周血单个核细胞(PBMCs)中NLRP3、凋亡相关微粒蛋白(ASC)、半胱氨酸蛋白酶1(caspase-1)mRNA及蛋白表达水平;比较两组研究对象TGF-β水平、促炎性细胞因子、血糖、血脂等水平。将研究组患者分为甲组与乙组,各50例,甲组接受瑞舒伐他汀治疗,乙组在甲组治疗基础上采用丹参通脉方干预,比较两组的临床疗效。结果两组研究对象的血脂水平、血糖水平、性别、吸烟史、年龄、体质量指数(BMI)、空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)及极低密度脂蛋白胆固醇(VLDL)水平比较,差异无统计学意义(P>0.05);与常规组研究对象比较,研究组患者平均动脉压(MAP)及高密度脂蛋白胆固醇(HDL-C)均显著升高;血清IL-1β,IL-18,TGF-β水平均显著升高(P<0.05);研究组研究对象ASCmRNA在PBMCs中的表达显著高于对照组(P<0.05),研究组患者NLRP3mRNA与caspase-1mRNA均与IL-18呈正相关,ASC与年龄、IL-1β、IL-18呈正相关;caspase-1与吸烟、IL-18呈正相关,IL-1β与TGF-β呈负相关。干预后,乙组患者临床疗效显著高于甲组(P<0.05)。结论血浆IL-1β,IL-18,TGF-β及PBMCs中NLRP3炎性小体与冠心病的发生、发展密切相关,冠心病患者予以丹参通脉方治疗可有效改善血脂水平,提高临床疗效。

Objective To investigate the clinical efficacy of oligomerized domain like receptor protein 3(NLRP3)inflammasome and Danshen Tongmai Formula in treating coronary heart disease,and their effects on the levels of interleukin-1β,IL-18,and transforming growth factor-β(TGF-β)in patients.Methods A total of 100 patients with coronary heart disease admitted to the hospital from February 2021 to February 2022(study group)and 100 individuals who came to the hospital for health check ups during the same period(routine group)were selected.Quantitative reverse transcription-polymerase chain reaction(RT-qPCR)and Western blot were used to detect the mRNA and protein expression levels of NLRP3,apoptosis related microprotein(ASC),and caspase-1 in peripheral blood mononuclear cells(PBMCs),respectively.The levels of TGF-β,pro-inflammatory cytokines,blood glucose,and blood lipids between the two groups were compared.The patients in the study group were divided into group A and group B,with 50 cases in each group.Group A received treatment with rosuvastatin,while group B received intervention with Danshen Tongmai Formula on this basis.The clinical efficacy of the two groups was compared.Results There was no statistically significant difference in the blood lipid levels,blood glucose levels,gender,smoking history,age,body mass index(BMI),fasting blood glucose(FBG),total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),and very low-density lipoprotein cholesterol(VLDL)levels between the two study groups(P>0.05).Compared with those in the routine group,the patients in the study group had significantly increased mean arterial pressure(MAP)and high-density lipoprotein cholesterol(HDL-C);the average levels of serum IL-1β,IL-18,and TGF-βwere significantly higher(P<0.05);the expression of ASCmRNA in PBMCs in the study group was significantly higher than in the control group(P<0.05).NLRP3mRNA and caspase-1mRNA were positively correlated with IL-18 in the study group,and ASC was positively correlated with age,IL-1β,and IL-18;caspase-1 was positively correlated with smoking and IL-18,while IL-1βwas negatively correlated with TGF-β.After intervention,the clinical efficacy in group B was significantly higher than that in group A(P<0.05).Conclusion Plasma IL-1β,IL-18,TGF-β,and NLRP3 inflammasome in PBMCs are closely related to the occurrence and development of coronary heart disease.Danshen Tongmai Formula in the treatment of coronary heart disease can effectively improve blood lipid levels and enhance clinical efficacy in patients.