复方中药对急性冠脉综合征患者雌激素受体基因与基质金属蛋白酶-9基因甲基化水平的影响

The Effect of Compound Chinese Medicine on Gene Methylation Level of ER Gene and MMP-9 Gene with ACS

目的探讨雌激素受体(ER)基因和基质金属蛋白酶-9(MMP-9)基因甲基化水平与急性冠脉综合征(ACS)的关系,观察经中西医结合治疗后的ACS患者(痰浊血瘀证)ER基因和MMP-9基因甲基化水平。方法将ACS(痰浊血瘀证)患者180例设为ACS组,另选健康正常人40例设为正常组。将ACS组患者随机分为对照组90例和治疗组90例,对照组给予PCI及西医常规治疗,治疗组于PCI术后在西医常规治疗的基础上给予中药汤剂口服,疗程为1个月,采用甲基化特异性聚合酶链反应(PCR)检测ACS患者治疗前后及健康人外周血细胞ER基因和MMP-9基因甲基化状态,比较正常组与ACS组、对照组治疗前后、治疗组治疗前后及治疗组与对照组治疗后ER基因和MMP-9基因甲基化水平。结果 1)ACS组ER基因甲基化率明显高于正常组(P<0.01),MMP-9基因甲基化率明显低于正常组(P<0.05);对照组与治疗组经治疗后其ER基因甲基化率均明显低于治疗前(P<0.05),对照组与治疗组经治疗后其MMP-9基因基化率均明显高于治疗前(P<0.05);治疗后治疗组ER基因甲基化率低于对照组(P<0.05)。结论 ACS的发生可能与ER基因的高甲基化状态和MMP-9基因的低甲基化状态有关,复方中药对ACS(痰浊血瘀证)患者MMP-9基因与ER基因甲基化水平的双向调节可能是其发挥临床效用的机制之一。

Objective: To study the relationship between the gene methylation level of estrogen receptor(ER),matrix metalloproteinase-9(MMP-9) and ACS,and observe the improvement of symptoms and the gene methylation level of ER and MMP-9 of combined treatment of traditional chinese and western medicine in treating ACS(phlegm and blood stasis type). Methods: 180 ACS patients diagnosed as phlegm and blood stasis type were selected as ACS group,40 normal people as the normal group. The 180 cases of ACS group were randomly divided into the control group(90 patients) and the treatment group(90 patients). The control group took PCI and the routine western medicine(Platelet inhibitors,ACEI and Statins,ect.). The treatment group were treated with Traditional Chinese Medicine. Treatment lasted for 1 months. MMP-9 and ER DNA methylation were detected before and after treatment in ACS patients and the normal group with methylation-specific PCR. The demethylation levels were compared among the normal group and ACS group,the control group before and after treatment,the treatment group before and after treatment,the treatment group and the control group after treatment. Results:Comparing with ACS group and the control group,there was the higher level of methylation rate of ER and the lower level of methylation rate of MMP-9 gene in the ACS patients,with statistical significance(P < 0.01). The level of methylation rate of ER gene in both the control group and the treatment group after treatment were significantly lower than pre-treatment,with statistical significance(P < 0.05). The levels of methylation rate of MMP-9gene in both the control group and the treatment group after treatment were significantly higher than pre-treatment,with statistical significance(P < 0.05). The methylation rate of ER gene of the treatment group after treatment was lower than that of the control group after treatment,with statistical significance(P < 0.05). Conclusion:The incidence of ACS may be associated with its high methylation status of ER gene and low methylation status of MMP-9 gene. Its regulating effect of the combination of traditional Chinese and Western medicine on the gene methylation level of ACS patients(Phlegm and blood stasis type) may be one of the mechanism of clinical effect.