从络风内动病机学说探讨络风宁2方抗心肌纤维化作用

Anti-myocardial fibrosis effect of Luofengning Granules Ⅱ:a discussion based on theory of internal stirring of collateral wind

目的观察络风宁2号方对心肾综合征患者心肌纤维化标志物的影响,以探索药物作用机制。方法依据随机对照的原则,收集2013年10月~2015年1月于北京中医药大学第-临床医学院心血管科120例心肾综合征患者,其中男性63例,女性57例,年龄35~85岁,平均(70.36±10.34.)岁;病程18~480个月,平均(129.95±43.29)个月。将104例心肾综合征的合格病例分为3组:全方组(常规治疗心力衰竭西药基础上口服络风宁2号免煎颗粒剂,n=35)、去风药组(常规治疗心力衰竭西药基础上口服去风药方免煎颗粒剂,n=36)、西药组(口服常规治疗心力衰竭的西药,n=33),疗程2个月。检测患者用药前后血浆可溶性基质裂解素2(sST2)、半乳糖凝集素-3(Gal-3)、N-末端脑钠肽前体(NT-proBNP)、半胱氨酸蛋白酶抑制剂C(CysC)、心肌肌钙蛋白I(cTnI)等心肌纤维化及心肾相关生物标志物的浓度变化。结果治疗前,3组患者sST2、Gal-3组间比较差异无统计学意义(P>0.05)。全方组、去风药组患者治疗后sST2水平较治疗前比较降低(P<0.05),而Gal-3无明显变化(P>0.05),治疗后,3组患者sST2水平两两比较差异无统计学意义(P>0.05)。治疗前3组患者NTproBNP、cTnI组间比较差异均无统计学意义(P>0.05)。与治疗前比较,全方组治疗后NT-proBNP降低明显(P<0.05),而去风药组、西药组改变不明显(P>0.05);治疗后,全方组、去风药组患者NTproBNP明显低于西药组,差异有统计学意义(P均<0.05)。3组患者治疗前后cTnI水平改变均不明显(P>0.05)。治疗前,3组患者CysC、eGFR组间比较差异均无统计学意义(P>0.05)。与治疗前比较,全方组治疗后CysC明显降低(P<0.05),而去风药组与西药组改变不明显(P>0.05);治疗后,全方组患者CysC水平显著低于西药组、去风药组,差异有统计学意义(P均<0.05)。与治疗前比较,治疗后3组eGFR均无明显变化(P>0.05);治疗后全方组患者eGFR高于去风药组(P<0.05)。结论络风宁2号方对心肌纤维化及心肾相关生物标志物产生了一定的影响,降低了sST2、NT-proBNP、(2ysC水平,对eGFR有提高作用。推测络风宁2号方可能通过改善甚至逆转心肌纤维化进程,从而发挥心肾保护作用。

Objective To observe the influence of Luofengning Granules Ⅱ （LG Ⅱ） on biomarkers of myocardial fibrosis in patients with cardiorenal syndrome （CRS）, and explore its mechanism. Methods CRS patients （n=120, male 63, female 57, aged from 35 to 85 and average age=70.36±10.34） were chosen from the Department of Cardiovascular Diseases in the First Clinical Medical School of Beijing University of Chinese Medicine from Oct. 2013 to Jan. 2015. The courses in CRS patients were from 18 m to 480 m and average course was （129.95±43.29） m. The eligible cases （n=104） were randomly divided into 3 groups： whole LG Ⅱ group （n=35, treated with routine drugs for heart failure and LG Ⅱ）, Qufeng Granules group （n=36, treated with routine drugs for heart failure and Qufeng Granules） and Western drug group （n=33, treated with routine drugs for heart failure）. The therapeutic course was for 2 m. The concentration changes of biomarkers related to myocardial fibrosis, heart and kidney were detected including stromelysin-2 （sST2）, galectin-3 （Gal-3）, N-terminal pro-brain natriuretic peptide （NT-proBNP）, cystatin C （CysC） and cardiac troponin I （cTnI）. Results The difference in levels of sST2 and Gal-3 had no statistical significance among 3 groups before treatment （P〉0.05）. The level of sST2 decreased （P〈0.05）, and level of Gal-3 had no significant changes （P〉0.05） in whole LG Ⅱ group and Qufeng Granules group after treatment, and difference in level of sST2 had no statistical significance in pairwise comparison among 3 groups （P〉0.05）. The difference in levels of NT-proBNP and cTnI had no statistical significance in pairwise comparison among 3 groups before treatment （P〉0.05）. The level of NT-proBNP decreased significantly in whole LG Ⅱ group （P〈0.05）, and had no significant changes in Qufeng Granules group and Western drug group after treatment （P〉0.05）. The level of NT-proBNP was significantly lower in whole LG Ⅱ group and Qufeng Granules group than that in Western drug group after treatment （all P〈0.05）. The level of cTnI had no significant changes in 3 groups before and after treatment （P〉0.05）. The difference in CysC and eGFR had no statistical significance in pairwise comparison among 3 groups before treatment （P〉0.05）. The level of CysC decreased significantly in whole LG Ⅱ group （P〈0.05） and had no significant changes in Qufeng Granules group and Western drug group （P〉0.05） after treatment. The level of CysC was significantly lower in whole LG Ⅱ group than that in Western drug group and Qufeng Granules group after treatment （all P〈0.05）. The level of eGFR had no significant changes in 3 groups （P〉0.05）, and was higher in whole LG Ⅱ group than that in Qufeng Granules group （P〈0.05） after treatment. Conclusion LG Ⅱ has some influence on myocardial fibrosis and biomarkers related to heart and kidney, and reduces levels of sST2, NT-proBNP and CysC and increases level of eGFR. It is speculated that LG Ⅱ may play the role of protecting heart and kidney through meliorating and even reversing the process of myocardial fibrosis.