Study on the Mechanism of Shuangshen Ningxin Capsules in Treating Coronary Microvascular Disease Based on Transcriptomic
10.19879/j.cnki.1005-5304.202404160
- VernacularTitle:基于转录组学研究双参宁心胶囊治疗冠状动脉微血管疾病作用机制
- Author:
Jing KANG
1
,
2
;
Lili YANG
;
Yue SHI
;
Yanlei MA
;
Hongxu MENG
;
Lei LI
Author Information
1. 中国中医科学院西苑医院基础医学研究所,中药药理北京市重点实验室,国家中医心血管疾病临床医学研究中心,北京 100091
2. 黑龙江中医药大学,黑龙江 哈尔滨 150040
- Keywords:
coronary microvascular disease;
Shuangshen Ningxin Capsules;
transcriptomics;
differentially expressed genes;
rats
- From:
Chinese Journal of Information on Traditional Chinese Medicine
2024;31(11):116-122
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the potential mechanism of Shuangshen Ningxin Capsules in the treatment of coronary microvascular disease(CMVD)using transcriptomics;To verify it.Methods Totally 30 male SD rats were randomly divided into sham-operation group,model group and Shuangshen Ningxin Capsules group,with 10 rats in each group.Shuangshen Ningxin Capsules group was given Shuangshen Ningxin Capsules solution(90 mg/kg)in advance for 7 days by gavage,while the sham-operation group and model group were given normal saline.CMVD rat model was established through left ventricular injection of embolic microspheres 2 hours after the last administration.The sham-operation group underwent open chest surgery and injected normal saline.24 hours after modeling,ultrasound was used to detect cardiac function[left ventricular systolic anterior wall thickness(LVAWs),left ventricular diastolic anterior wall thickness,left ventricular systolic posterior wall thickness,left ventricular diastolic posterior wall thickness,left ventricular end systolic diameter(LVIDs),left ventricular end diastolic diameter,left ventricular end diastolic volume,left ventricular end systolic volume(LVVs),stroke volume(SV),cardiac output(CO),ejection fraction(EF),fractional shortening(FS)];the reagent kit was used to detect the contents of serum CK,CK-MB and LDH;TTC staining was used to detect myocardial infarction area;HE staining was used to observe myocardial tissue morphology;transcriptome sequencing was used to detect common differentially expressed genes among the sham-operation group,model group and Shuangshen Ningxin Capsules group,GO and KEGG pathway enrichment analysis was performed on differentially expressed genes,and mRNA expression of differentially expressed genes were validated through RT-PCR.Results Compared with the sham-operation group,LVAWs,SV,CO,EF and FS of the model group significantly decreased,LVIDs and LVVs significantly increased(P<0.05,P<0.01),serum CK,CK-MB and LDH contents significantly increased(P<0.05,P<0.01),the area of myocardial infarction increased,the arrangement of myocardial cells was disorderly,and there was obvious infiltration of inflammatory cells.Compared with the model group,the rats in Shuangshen Ningxin Capsules group showed a significant decrease in LVIDs and LVVs,a significant increase in LVAWd,LVPWs,EF and FS(P<0.01),a significant decrease in serum CK,CK-MB and LDH contents(P<0.05,P<0.01),and a significant reduction in myocardial infarction area(P<0.01),the arrangement of myocardial cells was relatively neat,and the infiltration of inflammatory cells was reduced.The transcriptome sequencing results showed that there were 287 common differentially expressed genes among the sham-operation group,model group and Shuangshen Ningxin Capsules group,mainly enriched in chemokine signaling pathway,JAK-STAT signaling pathway,regulation of actin cytoskeleton,adrenergic signaling in cardiomyocytes,PPAR signaling pathway,NOD-like receptor signaling pathway,etc.RT-PCR validation results showed that Shuangshen Ningxin Capsules could significantly down-regulate the mRNA expressions of JAK2,STAT1,CXCL10,CXCL13 and CCR1 in myocardial tissue of model rats(P<0.05,P<0.01).Conclusion Shuangshen Ningxin Capsules can significantly improve cardiac function and reduce myocardial infarction area in CMVD rats,possibly by inhibiting the expressions of JAK-STAT signaling pathway JAK2 and STAT1,reducing the expressions of chemokines and their receptors(CXCL10,CXCL13,CCR1),reducing the recruitment of inflammatory cells,and exerting anti-inflammatory effects.
