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Mechanism of salidroside preventing myocardial fibrosis based on TLR4-mediated pyroptosis pathway
- ZHONGGUO YAOFANG Vol. 34, Issue 9, Pages: 1053-1059(2023)
- 作者机构：
1.南京中医药大学附属中西医结合医院心胸外科，南京 210028
2.江苏省中医药研究院，南京 210028
3.南京中医药大学中医学院/中西医结合学院，南京 210046
4.南京中医药大学附属中西医结合医院普外科，南京 210028
- 作者简介：
- 基金信息：
DOI：10.6039/j.issn.1001-0408.2023.09.06
CLC： R285;R542.2+3Published：15 May 2023，
Received：31 October 2022，
Revised：20 December 2022，
扫 描 看 全 文
温方军,高磊,胡益敏等.基于TLR4介导的细胞焦亡通路研究红景天苷预防心肌纤维化的作用机制 Δ[J].中国药房,2023,34(09):1053-1059.
WEN Fangjun,GAO Lei,HU Yimin,et al.Mechanism of salidroside preventing myocardial fibrosis based on TLR4-mediated pyroptosis pathway[J].ZHONGGUO YAOFANG,2023,34(09):1053-1059.
温方军,高磊,胡益敏等.基于TLR4介导的细胞焦亡通路研究红景天苷预防心肌纤维化的作用机制 Δ[J].中国药房,2023,34(09):1053-1059. DOI： 10.6039/j.issn.1001-0408.2023.09.06.
WEN Fangjun,GAO Lei,HU Yimin,et al.Mechanism of salidroside preventing myocardial fibrosis based on TLR4-mediated pyroptosis pathway[J].ZHONGGUO YAOFANG,2023,34(09):1053-1059. DOI： 10.6039/j.issn.1001-0408.2023.09.06.
摘要
目的
2
探讨红景天苷对小鼠心肌纤维化和焦亡的影响及潜在的作用机制。
方法
2
将小鼠随机分为对照组、模型组和红景天苷低、中、高剂量组，每组各10只。除对照组外，其余各组小鼠皮下注射异丙肾上腺素5 mg/（kg·d）造模。自造模之日起，红景天苷低、中、高剂量组小鼠每日灌胃红景天苷10、30、50 mg/kg，对照组和模型组小鼠每日灌胃生理盐水10 mL/kg，连续14 d。末次给药后处死小鼠，以苏木素-伊红染色法观察小鼠心肌组织病理变化并计算心肌细胞横径，Masson、Sirius Red染色法观察小鼠心肌组织纤维化程度并计算心肌胶原容积分数（CVF），实时荧光定量PCR法检测小鼠心肌组织中Ⅰ型胶原蛋白（Col Ⅰ）、
α
-平滑肌肌动蛋白（
α
-SMA）、Toll样受体4（TLR4）、NOD样受体蛋白3（NLRP3）、半胱氨酸蛋白酶1（caspase-1）、消皮素D（GSDMD）的mRNA表达水平，Western blot法和免疫组织化学法检测小鼠心肌组织中Col Ⅰ、
α
-SMA、TLR4、NLRP3、caspase-1、GSDMD的总蛋白表达水平及蛋白阳性细胞积分。
结果
2
与对照组比较，模型组小鼠心肌细胞体积增大，心肌纤维排列紊乱，细胞基质明显增加，心肌组织中CVF显著升高，Col Ⅰ、
α
-SMA、TLR4、NLRP3、caspase-1、GSDMD的mRNA、总蛋白表达水平及蛋白阳性细胞积分均显著升高（
P
＜0.01）。与模型组比较，红景天苷中、高剂量组小鼠心肌细胞形态较清晰，心肌纤维化程度较低，心肌组织中以上指标水平均不同程度逆转，尤其是红景天苷高剂量组逆转程度最显著（
P
＜0.05或
P
＜0.01）。此外，红景天苷低剂量组部分纤维化和焦亡相关指标也在一定程度上逆转。
结论
2
红景天苷对心肌纤维化的发生、发展有明显的预防作用，其机制可能是通过抑制TLR4介导的心肌细胞焦亡通路激活。
Abstract
OBJECTIVE
2
To investigate the effects of salidroside （Sal） on myocardial fibrosis and pyroptosis and its potential mechanism.
METHODS
2
The mice were randomly divided into control group， model group and Sal low-dose， medium-dose and high-dose groups， with 10 mice in each group. Except for the control group， the mice in other groups were injected subcutaneously with isoproterenol 5 mg/（kg·d）to prepare the myocardial fibrosis model. Since modeling， mice in the Sal low-dose， medium-dose and high-dose groups were given 10， 30 and 50 mg/kg of Sal by intragastric administration every day； control group and model group were given 10 mL/kg of normal saline by intragastric administration every day， for 14 consecutive days. After the last medication， the mice were sacrificed； hematoxylin-eosin staining was used to observe pathological change of myocardial tissue and calculate the diameter of myocardial cell； Masson and Sirius Red staining were used to observe the degree of myocardial fibrosis in mice and calculate the collagen volume fraction （CVF）； quantitative real-time PCR was performed to detect the mRNA expressions of collagen type Ⅰ （Col Ⅰ），
α
-smooth muscle actin （
α
-SMA）， Toll-like receptor 4 （TLR4）， NOD-like receptor pyrin domain containing 3 （NLRP3）， caspase-1 and gasdermin D （GSDMD） in myocardial tissues. The total protein expressions of Col Ⅰ，
α
-SMA， TLR4， NLRP3， caspase-1 and GSDMD in myocardial tissues and protein-positive cell score were measured by Western blot assay and immunohistochemistry.
RESULTS
2
Compared with control group， the myocardial cells in the model group were enlarged， the arrangement of myocardial fibers was disordered， the matrix metabolism was significantly increased， the CVF in myocardial tissue was significantly increased， and the mRNA and protein expression levels of Col Ⅰ，
α
-SMA， TLR4， NLRP3， caspase-1 and GSDMD were elevated and protein-positive cell score was increased significantly （
P
＜0.01）. Compared with model group， the myocardial cell morphology was clearer， myocardial fibrosis was alleviated， and the levels of the above indicators in myocardial tissue of Sal medium-dose and high-dose groups had been reversed to varying degrees， especially in Sal high-dose group（
P
＜0.05 or
P
＜0.01）. In addition， the Sal low-dose group also reversed some fibrosis and pyroptosis-related indicators to some extent.
CONCLUSIONS
2
Sal can significantly prevent the occurrence and development of myocardial fibrosis， and the mechanism of action may be related to the inhibition of TLR4-mediated pyroptosis pathway in myocardial tissue.
关键词
红景天苷心肌纤维化焦亡Toll样受体4NOD样受体蛋白3
Keywords
myocardial fibrosispyroptosisToll-like receptor 4NOD-like receptor pyrin domain containing 3
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