The Effect of <italic style="font-style: italic">Shenqi Jianxin Formula</italic> （参芪健心方） on Cardiomyocyte Pyroptosis in Chronic Heart Failure Model Rats Based on the NLRP3/Caspase-1 Signaling Pathway

LIANG Guoqing; XIA Ran; WANG Yinyan; LIU Pan; ZHANG Jun; DAI Xiaohua

doi:10.13288/j.11-2166/r.2024.01.017

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The Effect of Shenqi Jianxin Formula （参芪健心方） on Cardiomyocyte Pyroptosis in Chronic Heart Failure Model Rats Based on the NLRP3/Caspase-1 Signaling Pathway

更新时间：2024-01-09

- The Effect of Shenqi Jianxin Formula （参芪健心方） on Cardiomyocyte Pyroptosis in Chronic Heart Failure Model Rats Based on the NLRP3/Caspase-1 Signaling Pathway
- Journal of Traditional Chinese Medicine Vol. 65, Issue 1, Pages: 94-102(2024)
- 作者机构：
  
  1.安徽中医药大学第一附属医院，安徽省合肥市梅山路117号，230031
  2.安徽中医药大学中医学院
  3.安徽省中西医结合医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2024.01.017
  CLC：
- Received：06 August 2023，
  
  Revised：2023-10-16，
  
  Published：02 January 2024
- 稿件说明：
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梁国庆,夏冉,王银燕等.基于NLRP3/Caspase-1信号通路探讨参芪健心方对慢性心力衰竭模型大鼠心肌细胞焦亡的影响[J].中医杂志,2024,65(01):94-102.

LIANG Guoqing,XIA Ran,WANG Yinyan,et al.The Effect of Shenqi Jianxin Formula （参芪健心方） on Cardiomyocyte Pyroptosis in Chronic Heart Failure Model Rats Based on the NLRP3/Caspase-1 Signaling Pathway[J].Journal of Traditional Chinese Medicine,2024,65(01):94-102.
梁国庆,夏冉,王银燕等.基于NLRP3/Caspase-1信号通路探讨参芪健心方对慢性心力衰竭模型大鼠心肌细胞焦亡的影响[J].中医杂志,2024,65(01):94-102. DOI： 10.13288/j.11-2166/r.2024.01.017.

LIANG Guoqing,XIA Ran,WANG Yinyan,et al.The Effect of Shenqi Jianxin Formula （参芪健心方） on Cardiomyocyte Pyroptosis in Chronic Heart Failure Model Rats Based on the NLRP3/Caspase-1 Signaling Pathway[J].Journal of Traditional Chinese Medicine,2024,65(01):94-102. DOI： 10.13288/j.11-2166/r.2024.01.017.

摘要

目的

从细胞焦亡角度探讨参芪健心方治疗慢性心力衰竭的可能作用机制。

方法

将52只大鼠随机分为假手术组8只和造模组44只，造模组大鼠结扎左冠状动脉前降支构建慢性心力衰竭大鼠模型。将造模成功的40只大鼠随机分为模型组、沙库巴曲缬沙坦组、参芪健心方组、MCC950组及参芪健心方+MCC950组，每组8只。参芪健心方组予参芪健心方药液7.4 g/（kg·d）灌胃；沙库巴曲缬沙坦组予沙库巴曲缬沙坦混悬液68 mg/（kg·d）灌胃；MCC950组予以腹腔注射MCC950 10 mg/kg，隔日1次；参芪健心方+MCC950组予参芪健心方7.4 g/（kg·d）灌胃，再腹腔注射MCC950 10 mg/kg隔日1次；假手术组和模型组予生理盐水10 ml/（kg·d）灌胃。各组连续干预3周后，ELISA法检测大鼠血清脑B型钠尿肽（BNP）、肌酸激酶同工酶MB（CK-MB）、白细胞介素1β（IL-1β）、白细胞介素18（IL-18）水平；HE染色、MASSON染色观察大鼠心肌病理改变。除沙库巴曲缬沙坦组外，Western blot法检测各组大鼠心肌NOD样受体蛋白3（NLRP3）、半胱氨酸天冬氨酸蛋白酶1（Caspase-1）、凋亡相关斑点样蛋白（ASC）蛋白表达，RT-PCR法检测NLRP3、Caspase-1 mRNA的表达。

结果

与假手术组比较，模型组大鼠HE染色示心肌损伤明显，MASSON染色示胶原纤维化面积增大，血清BNP、CK-MB、IL-1β、IL-18含量，心肌组织NLRP3、Caspase-1、ASC蛋白表达及NLRP3、Caspase-1 mRNA表达均升高（

＜0.05）。与模型组比较，参芪健心方组、沙库巴曲缬沙坦组、MCC950组及参芪健心方+MCC950组大鼠心肌细胞损伤减轻，胶原纤维化面积减小，血清BNP、CK-MB、IL-1β、IL-18含量均降低；除沙库巴曲缬沙坦组未检测外，其余三个干预组心肌组织NLRP3、Caspase-1、ASC蛋白表达及NLRP3、Caspase-1 mRNA表达均降低（

＜0.05）。与参芪健心方组比较，MCC950组、参芪健心方+MCC950组血清IL-1β、IL-18含量减少，胶原纤维化面积减小，心肌组织NLPR3、Caspase-1蛋白表达及Caspase-1 mRNA表达均降低，参芪健心方+MCC950组ASC蛋白、NLRP3 mRNA表达亦降低（

＜0.05）；与MCC950组比较，参芪健心方+MCC950组血清IL-18水平下降，胶原纤维化面积减小，NLRP3、Caspase-1 mRNA表达降低（

＜0.05）。

结论

参芪健心方能够有效改善慢性心力衰竭模型大鼠心肌损伤，其机制可能与其通过NLRP3/Caspase-1通路抑制心肌细胞焦亡，减轻心肌内炎症水平有关，且MCC950联合参芪健心方能更有效抑制心肌细胞焦亡，治疗效果优于单一MCC950和参芪健心方。

Abstract

Objective

To investigate the possible mechanism of

Shenqi Jianxin Formula

（参芪健心方） in the treatment of chronic heart failure （CHF） from the perspective of pyroptosis.

Methods

Fifty-two rats were randomly divided into sham operation group （n=8） and modeling group （n=44）. In the modeling group， the anterior descending branch of the left coronary artery was ligated to construct CHF rat model. Forty successfully-modelled rats were randomly divided into model group， Entresto group，

Shenqi Jianxin Formula

group， MCC950 group and the combination group （

Shenqi Jianxin Formula

plus MCC950）， with 8 rats in each group. In

Shenqi Jianxin Formula

group， 7.4 g/（kg·d） of

Shenqi Jianxin Formula

was given by gavage， while in Entresto group， 68 mg/（kg·d） of Entresto suspension was given by gavage； in MCC950 group， MCC950 was injected intraperitoneally with 10 mg/kg once every other day， and in the combination group， 7.4 g/（kg·d） of

Shenqi Jianxin Formula

was given by gavage， and MCC950 was injected intraperitoneally with 10 mg/kg once every other day； 10 ml/（kg·d） of saline was given by gavage in the sham operation group and the model group. After 3 weeks of continuous intervention， serum brain B-type natriuretic peptide （BNP）， creatine kinase isoenzyme MB （CK-MB）， interleukin 1β （IL-1β）， and interleukin 18 （IL-18） levels were detected by ELISA； HE staining and MASSON staining were used to observe pathological changes in rat myocardium. Except for the Entresto group， western blot technique was used to detect the expression of NOD-like receptor protein 3 （NLRP3）， caspase-1， and apoptosis-associated speck-like protein possessing a caspase-recruiting domain （ASC）； RT-PCR was used to detect the expression of NLRP3 and caspase-1 mRNA.

Results

Compared with the sham operation group， HE staining of rats in the model group showed obvious myocardial injury， while MASSON staining showed increased area of collagen fibrosis， and serum BNP， CK-MB， IL-1β， IL-18， myocardial tissue NLRP3， caspase-1， ASC protein expression and NLRP3， caspase-1 mRNA expression were all elevated （

＜0.05）. Compared with those in the model group， cardiomyocyte injury of rats and collagen fibrosis area were reduced， and serum BNP， CK-MB， IL-1β， and IL-18 contents were all reduced in

Shenqi Jianxin Formula

group， Entresto group， MCC950 group， and the combination group； except for Entresto group， myocardial tissue NLRP3， caspase-1， ASC protein expression and NLRP3， caspase-1 mRNA expression were reduced in the remaining three medication group （

＜0.05）. Compared with

Shenqi Jianxin Formula

group， the MCC950 group and the combination group showed decreased serum IL-1β and IL-18 content， collagen fibrosis area， myocardial tissue NLPR3， caspase-1 protein expression， and caspase-1 mRNA expression， and decreased ASC and NLRP3 mRNA expression was shown in the combination group （

＜0.05）. Compared with MCC950 group， collagen fibrosis area was reduced， and serum IL-18 content， NLRP3， caspase-1 mRNA expression were reduced in the combination group （

＜0.05）.

Conclusion

Shenqi Jianxin Formula

can effectively improve the myocardial injury and heart failure in rats with CHF， and its mechanism may be related to the inhibition of cardiomyocyte pyroptosis through NLPR3/Caspase-1 pathway to reduce the level of intramyocardial inflammation. The combined use of MCC950 with

Shenqi Jianxin Formula

could more effectively inhibite myocardial pyroptosis， with better therapeutic result than single use of each part.

关键词

Keywords

references

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The Effect of Shenqi Jianxin Formula （参芪健心方） on Cardiomyocyte Pyroptosis in Chronic Heart Failure Model Rats Based on the NLRP3/Caspase-1 Signaling Pathway

DOI：10.13288/j.11-2166/r.2024.01.017

摘要

Abstract

关键词

Keywords

references