基于肠道菌群的丹参-红花药对抗心肌缺血机制探讨

Mechanism of Salviae Miltiorrhizae Radix et Rhizoma-Carthami Flos Drug Pairs Against Myocardial Ischemia Based on Intestinal Bacteria

目的探讨丹参-红花药对抗心肌缺血的机制。方法将60只SD雄性大鼠随机分为空白对照组(A组,等体积纯净水)、模型组(B组,等体积纯净水)、复方丹参滴丸组(C组,73 mg/kg)及丹参-红花低、中、高剂量组(D_(1)组、D_(2)组、D_(3)组,原药材4,8,16 g/kg),各10只,各组大鼠灌胃给予相应药物或纯净水,每天1次,连续7 d。于第6天、第7天灌胃给药1 h后,除A组外,其余各组均皮下注射盐酸异丙肾上腺素(85 mg/kg)以复制急性心肌缺血大鼠模型。观察大鼠心肌病理形态、心肌细胞凋亡情况,采用酶联免疫吸附法检测大鼠心肌酶水平;采用多指标综合指数法计算各组总效应值和偏最小二乘回归分析(PLS-DA)得分,筛选效果最佳的剂量组进行肠道菌群多样性分析。结果D_(3)组的综合指数最高(7.68),其次是D_(2)组(7.18),D_(3)组和D_(2)组PLS-DA得分差异较小,选用D_(2)组进行肠道菌群多样性分析;与B组比较,D_(2)组放线菌门、TM7菌门、厚壁菌门/拟杆菌门、乳杆菌属、棒状杆菌属、葡萄球菌属和SMB53菌属的相对丰度显著升高(P<0.05或P<0.01),拟杆菌门、软壁菌门、脱铁杆菌门、颤螺菌属和罗斯氏菌属的相对丰度显著降低(P<0.05或P<0.01)。结论丹参-红花药对可能通过调节肠道菌群而发挥抗心肌缺血的作用。

Objective To investigate the mechanism of Salviae Miltiorrhizae Radix et Rhizoma-Carthami Flos drug pairs against myocardial ischemia.Methods A total of 60 male SD rats were randomly divided into the blank control group(group A,equal volume purified water),the model group(group B,equal volume purified water),the compound Danshen Dropping Pills group(group C,73 mg/kg)and the Salviae Miltiorrhizae Radix et Rhizoma-Carthami Flos low-,medium-and high-dose groups(group D_(1),group D_(2),group D_(3),4,8,16 g raw medicine/kg respectively),with ten rats in each group.Rats in each group were given corresponding drugs or purified water by gavaging once a day for seven days.On the 6th and 7th day after intragastric administration for 1 h,isoproterenol hydrochloride(85 mg/kg)was injected subcutaneously in all groups except group A to replicate the acute myocardial ischemia rat model.The myocardial pathological morphology and cardiomyocyte apoptosis in rats were observed,and the level of myocardial enzyme in rats was detected by enzyme-linked immunosorbent assay(ELISA).The total effect value and partial least squares discriminant analysis(PLS-DA)score of each group were calculated by multi-index comprehensive evaluation method,and the group with the best effect was selected for intestinal bacteria diversity analysis.Results The comprehensive index of group D_(3) was the highest(7.68),followed by group D_(2)(7.18),there was little difference between the PLS-DA score of group D_(3) and group D_(2),and group D_(2) was selected for intestinal bacteria diversity analysis.Compared with those of group B,the relative abundances of Actinomycetes,TM7,Firmicutes/Bacteroidetes,Lactobacillus,Corynebacterium,Staphylococcus and SMB53 in group D_(2) were significantly increased(P<0.05 or P<0.01),while the relative abundances of Bacteroidetes,Tenericutes,Deferribacteres,Oscillosporia and Rothia were significantly decreased(P<0.05 or P<0.01).Conclusion Salviae Miltiorrhizae Radix et Rhizoma-Carthami Flos drug pairs can against myocardial ischemia by regulating intestinal bacteria.