基于TLR4/NF-κB/NLRP3通路探讨参芪调肾方改善CSE诱导小鼠肺泡巨噬细胞炎症反应的作用机制

目的:基于TLR4/NF-κB/NLRP3通路探讨参芪调肾方(SQTS)改善香烟烟雾提取物(Cigarette smoking extract,CSE)诱导小鼠肺泡巨噬细胞(MH-S)炎症反应的作用机制。方法:以MH-S细胞为研究对象,通过CCK-8法分析SQTS对MH-S细胞的安全性及药效浓度;随后MH-S分为空白组、模型组(8%CSE)和SQTS低、中、高剂量组(40、80、160 mg/L)。ELISA检测细胞上清TNF-α、IL-1β和IL-6含量;DCFH-DA荧光探针法检测细胞中ROS水平;Westernblot检测TLR4/NF-κB/NLRP3通路蛋白的表达,使用TLR4抑制剂TAK-242验证SQTS在TLR4/NF-κB/NLRP3通路上的作用。结果:与空白组比较,CSE组细胞活力降低,炎症因子TNF-α、IL-1β和IL-6的含量增加(P<0.05),ROS荧光表达水平显著升高(P<0.01),TLR4/NF-κB/NLRP3通路蛋白表达明显增加(P<0.05);与模型组比较,参芪调肾方各剂量组细胞活力升高,以上各指标表达水平均有所降低(P<0.05),且TAK-242各组细胞TLR4/NF-κB/NLRP3通路蛋白减少(P<0.05)。结论:参芪调肾方可减轻CSE诱导的MH-S细胞的炎症反应,其机制可能与抑制TLR4/NF-κB/NLRP3通路有关。

To investigate the effect of Shenqi Tiaoshen Formula on CSE induced inflammatory response of MH-S cells based on TLR4/NF-kB/NLRP3 pathway

Objective:To study the effects of Shenqi Tiaoshen Formula(SQTS)on the inflammatory response of MH-S cells induced by cigarette smoking extract(CSE)and its mechanism based on TLR4/NF-kB/NLRP3 pathway.Methods:MH-S cells were used as subjects to evaluate cell viability by CCK-8 method.The levels of TNF-α,IL-1βand IL-6 in the supernatant were detected by ELISA.ROS were detected by DCFH-DA fluorescence probe.Western blotting was used to detect the expression of TLR4/NF-kB/NLRP3 pathway protein,and TAK-242,a TLR4 inhibitor,was used to verify the role of SQTS in the TLR4/NF-kB/NLRP3 pathway.Results:Compared with blank group,the cell survival rate of CSE group was decreased,and the contents of inflammatory cytokines TNF-α,IL-1βand IL-6 were increased(P<0.05),ROS fluorescence expression level was significantly increased(P<0.01),TLR4/NF-kB/NLRP3 pathway protein expression was significantly increased(P<0.05);Compared with CSE group,the survival rate of cells in SQTS groups was increased,and the expression levels of the above indexes were decreased(P<0.05),and TLR4/NF-kB/NLRP3 pathway protein decreased in TAK-242 groups(P<0.05).Conclusion:SQTS can reduce the inflammatory response of MH-S cells induced by CSE by inhibiting TLR4/NF-kB/NLRP3 pathway.

稳心颗粒对比西药抗心律失常药物治疗心房纤颤临床疗效的Meta分析

该研究旨在系统评价稳心颗粒对比西药治疗心房纤颤的疗效及安全性,共检索中国知网、万方、维普、CBM、Cochrane Library、Web of Science、PubMed、EMbase 8个电子数据库,检索日期从建库至2019年1月10日。由2位评价员按纳入并筛选文献后,研究采用RevMan 5.3软件进行分析。研究纳入42项RCT研究(4 657例患者)。结果,联合稳心颗粒对比西药临床疗效OR=3.37,95%CI[2.69,4.22],I2=0%,P<0.000 01;复律疗效OR=2.32,95%CI[1.67,3.22],I2=0%,P<0.000 01;Pd MD=-5.48,95%CI[-7.32,-3.64],I2=0%,P<0.000 01;Pmax MD=-9.91,95%CI[-12.86,-6.95],I2=0%,P<0.000 01。联合稳心颗粒对比胺碘酮临床疗效OR=2.89,95%CI[1.96,4.26],I2=44%,P<0.000 01;维持窦律疗效OR=2.58,95%CI[1.82,3.66],I2=3%,P<0.000 01。稳心颗粒单独对比胺碘酮疗效分析的临床疗效OR=0.88,95%CI[0.53,1.46],I2=0%,P=0.63。联合应用稳心颗粒治疗房颤具有显著疗效,各项主要临床疗效指标均优于单独应用西药抗心律失常药物,无证据表明单独服用稳心颗粒可以带来更多获益。