Observation on the mechanism of Sanshen Tongmai Mixture on chronic heart failure rats

TENG Fei; WANG Zhen-yu; LI Ran

doi:10.16025/j.1674-1307.2023.09.006

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Observation on the mechanism of Sanshen Tongmai Mixture on chronic heart failure rats

更新时间：2023-10-23

- Observation on the mechanism of Sanshen Tongmai Mixture on chronic heart failure rats
- Beijing Journal of Traditional Chinese Medicine Vol. 42, Issue 9, Pages: 958-965(2023)
- 作者机构：
  
  1.首都医科大学附属北京中医医院干部保健科，北京 100010
- 作者简介：
- 基金信息：
- DOI：10.16025/j.1674-1307.2023.09.006
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滕菲，王振裕，李然.三参通脉合剂对慢性心力衰竭大鼠的作用机制观察［J］.北京中医药，2023，42（9）：958-965.

TENG Fei,WANG Zhen-yu,LI Ran.Observation on the mechanism of Sanshen Tongmai Mixture on chronic heart failure rats[J]. Beijing Journal of Traditional Chinese Medicine,2023,42(09):958-965.
滕菲，王振裕，李然.三参通脉合剂对慢性心力衰竭大鼠的作用机制观察［J］.北京中医药，2023，42（9）：958-965. DOI： 10.16025/j.1674-1307.2023.09.006.

TENG Fei,WANG Zhen-yu,LI Ran.Observation on the mechanism of Sanshen Tongmai Mixture on chronic heart failure rats[J]. Beijing Journal of Traditional Chinese Medicine,2023,42(09):958-965. DOI： 10.16025/j.1674-1307.2023.09.006.

摘要

目的,2,探讨三参通脉合剂对慢性心力衰竭（CHF）大鼠的治疗作用及其机制。,方法,2,共104只大鼠，随机取8只大鼠作为正常对照组，灌服生理盐水1 mL/100 g体质量，1次/d。将其余96只大鼠随机分为模型组、microRNA146a（miR146a） mimic组、miR146a inhibitor组、药物高剂量组、药物中剂量组、药物低剂量组、miR146a mimic+药物高剂量组、miR146a mimic+药物中剂量组、miR146a mimic+药物低剂量组、miR146a inhibitor+药物高剂量组、miR146a inhibitor+药物中剂量组、miR146a inhibitor+药物低剂量组，每组8只。各miR146a mimic组先行在大鼠心肌中注射miR146a mimic 0.2 μL/g，各miR146a inhibitor组先行在大鼠心肌中注射miR146a inhibitor 0.2 μL/g，24 h后再制作CHF模型，模型组、miR146a mimic组、miR146a inhibitor组、药物各剂量组、miR146a mimic+药物各剂量组、miR146a inhibitor+药物各剂量组均在同一天造模。造模成功后，药物高、中、低剂量组分别灌服三参通脉合剂药液3、2、1 mL/100 g体质量，连续灌服6周。对比各组一般情况，超声心动图指标［左心室收缩末期内径（LVIDs）、左心室舒张末期内径（LVIDd）、收缩末期室间隔厚度（IVSs）、舒张期室间隔厚度（IVSd）、左室射血分数（LVEF）及左室轴缩短率（LVFS）］，心肌组织病理变化，大鼠血清N端脑钠肽前体（Nt-proBNP）、超敏C反应蛋白（Hs-CRP）、血管紧张素Ⅱ（Angiotensin Ⅱ）水平，心肌组织NF-κB（核转录因子κB）、TRAF6（肿瘤坏死因子受体相关因子） mRNA表达。,结果,2,与正常对照组相比，模型组及miR146a inhibitor组一般情况较差，心肌炎症反应以及心功能损伤程度较重，心肌细胞变性、坏死、纤维增生较重。与模型组相比，药物组、miR146a mimic组、miR146a mimic+药物组对Nt-proBNP、NO、Hs-CRP、Angiotensin Ⅱ水平均有正向干预作用（,P,<,0.05），超声心动指标均改善（,P,<,0.05）。而miR146a inhibitor组与正常对照组及模型组比较，对Nt-proBNP、NO、Hs-CRP、Angiotensin Ⅱ水平均有负向干预作用（,P,<,0.05）。但miR146a inhibitor+药物高剂量组与模型组对比，Nt-proBNP及Angiotensin Ⅱ水平均降低，差异有统计学意义（,P,<,0.05）。同时，与模型组相比，miR146a mimic组和高剂量三参通脉药物组NF-κB、TRAF6 mRNA表达降低。,结论,2,三参通脉合剂能有效改善CHF大鼠的心功能和心肌活性，该作用可能与激活miR146a表达，从而下调NF-κB、TRAF6表达有关。

Abstract

Objective,2,To explore the effect and mechanism of Sanshen Tongmai Mixture on chronic heart failure （CHF）.,Method,2,Eight rats were randomly selected as the normal control group， fed normally， and given saline 1 mL/100 g once a day.The other 96 rats were randomly divided into model group， microRNA146a mimic group， micro146a inhibitor group， high-dose drug group， medium dose drug group， low dose drug group， microRNA146a mimic+ high-dose group， microRNA146a mimic+ medium dose drug group， microRNA146a mimic+ low-dose drug group， microRNA146a inhibitor+ high-dose drug group， microRNA146a inhibitor+ medium dose drug group MicroRNA146a inhibitor+low-dose drug group with 8 in each group.Each microRNA146a mimic group was injected microRNA146amimic 0.2 μL/g into rat myocardium， and each microRNA146a inhibitor group injected microRNA146a inhibitor 0.2 μL/g into rat myocardium， 24 hours later，CHF model was made， the model group， high-dose drug group， medium-dose drug group and low-dose drug group were established on the same day. After modeling， the high-dose drug group， medium-dose drug group and low-dose drug group were given Sanshen Tongmai Mixture by gavage with 3，2，and 1 ml/100 g of Sanshen Tongmai mixture were respectively given orally for 6 weeks. The general conditions of the rats in each group were compared， including echocardiographic indexes ［left ventricular end-systolic diameter （LVIDs）， left ventricular end-diastolic diameter （LVIDd）， end-systolic interventricular septum thickness （IVSs）， diastolic interventricular septum thickness （IVSd）， left ventricular ejection fraction （LVEF） and left ventricular axial shortening rate （LVFS），pathological changes of myocardial tissue， serum levels of N-terminal pro-brain natriuretic peptide （NT-proBNP）， high-sensitivity C-reactive protein （Hs-CRP） and angiotensin II in rats， and expression of NF-κB and TRAF6 mRNA in myocardial tissue.,Result,2,Compared with the control group， the general condition of the model group and microRNA146a inhibitor rats was worse， with more severe myocarditis reactions and cardiac function damage， and more severe myocardial cell degeneration， necrosis， and fiber proliferation. Compared with the model group， the drug group，microRNA146a mimic group and the microRNA146a mimic+drug group both had a positive intervention effect on the levels of Nt proBNP， NO， Hs CRP， and Angiotensin Ⅱ （,P,<,0.05），echocardiographic indexes were all improved （,P,<,0.05）. Compared with the normal group and the model group， the microRNA146a inhibitor group had a negative intervention effect on the levels of Nt-proBNP， NO， Hs-CRP and Angiotensin Ⅱ （,P,<,0.05）.However， compared with the model group， the levels of Nt-proBNP and Angiotensin Ⅱ in the microRNA146a inhibitor+high-dose group decreased， and the difference was statistically significant （,P,<,0.05）.Meanwhile， both microRNA146a mimic and high-dose Sanshen Tongmai drug groups significantly reduced NF-κB，TRAF6 mRNA expression.,Conclusion,2,Sanshen Tongmai Mixture can effectively improve cardiac function and myocardial activity in rats with chronic heart failure， and this effect may be related to the activation of microRNA146a expression， thus down-regulating the expression of NF-κB and TRAF6.

关键词

慢性心力衰竭三参通脉合剂microRNA146aNF-κB/TRAF6细胞通路大鼠

Keywords

Chronic heart failureSanshen Tongmai MixturemicroRNA146aNF-κB/TRAF6 cell pathwayrat

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