[1]刘文秀 郭雨桐 孙雪 宋琳琳 刘越 丁雪.Calhex231通过焦亡改善大鼠心肌梗死面积大小及心脏纤维化[J].心血管病学进展,2024,(4):379.[doi:10.16806/j.cnki.issn.1004-3934.2024.04.000]
　LIU Wenxiu,GUO Yutong,SUN Xue,et al.Calhex231 Attenuates Rat Myocardial Infarct Size and Fibrosis by Suppressing Pyroptosis[J].Advances in Cardiovascular Diseases,2024,(4):379.[doi:10.16806/j.cnki.issn.1004-3934.2024.04.000]
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Calhex231通过焦亡改善大鼠心肌梗死面积大小及心脏纤维化()
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《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2024年4期
页码:
379
栏目:
论著
出版日期:
2024-04-25

文章信息/Info

Title:
Calhex231 Attenuates Rat Myocardial Infarct Size and Fibrosis by Suppressing Pyroptosis
作者:
刘文秀 郭雨桐 孙雪 宋琳琳 刘越 丁雪
(哈尔滨医科大学附属第一医院 心内科,黑龙江 哈尔滨 150001)
Author(s):
LIU Wenxiu; GUO Yutong; SUN Xue; SONG Linlin; LIU Yue; DING Xue
(Department of Cardiology,The First Affiliated Hospital of Harbin Medical University,Harbin 150001,Heilongjiang,China)
关键词:
钙敏感受体; 焦亡; 心肌梗死; 纤维化
Keywords:
Calcium-sensing receptor;  Pyroptosis;  Myocardial infarction;  Fibrosis
DOI:
10.16806/j.cnki.issn.1004-3934.2024.04.000
摘要:
目的??究钙敏感受体（CaSR）负变构调节剂Calhex231是否能改善心肌梗死（MI）大鼠的MI面积和心脏纤维化。方法??康 Wistar大鼠随机分为3组：sham组、MI组和MI+Calhex231组。TTC染色评估MI面积和坏死情况。Masson染色、免疫组化及电镜检查心肌纤维化、胶原Ⅲ及成纤维细胞胶原合成情况。免疫荧光和Western blot检测CaSR表达变化。Western blot检测含 NOD样受体 热蛋白结构域相关蛋白3（NLRP3）、半胱天冬酶-1（Casp-1）、gasdermin D（GSDMD）、GSDMD N-末端结构域（NT-GSDMD）和白细胞介素-1β（IL-1β）的蛋白表达变化。并采用免疫组化法评估NT-GSDMD和IL-1β的表达情况。结果?#160 与sham组相比， MI组大鼠MI面积和纤维化明显增加，心肌组织Ⅲ型胶原沉积和成纤维细胞胶原合成明显增加，而且CaSR、NLRP3、Casp-1、GSDMD、NT-GSDMD和IL-1β表达水平也明显升高。进一步免疫组化染色确认了NT-GSDMD和IL-1β表达增加。MI+Calhex231组与MI组相比较，Calhex231可抑制上述改变。结论?#160 Calhex231可通过CaSR抑制焦亡和Ⅲ型胶原沉积，改善大鼠MI面积和心脏纤维化，有助于Calhex231在心肌纤维化疾病中临床转化。
Abstract:
Objective?#160 Calcium-sensing receptor (CaSR) plays an important role in the development of myocardial infarction (MI). Thus ,we investigated whether Calhex231,a negative allosteric modulator of CaSR,could protect the myocardium in a rat MI model. Methods?#160 Wistar rats were randomly divided into three groups: sham,MI and MI+Calhex231. Myocardial infarct size and necrosis were assessed by TTC staining. Myocardial fibrosis,collagen Ⅲ and collagen synthesis of fibroblasts were examined by Masson staining, immunohistochemistry and electron microscopy. CaSR expression was detected by b oth immunofluorescence and Western blot analysis. Protein expression levels of t he NOD-like receptor thermal protein domain associated protein 3 (NLRP3) , caspase-1 ( Casp-1), gasdermin D (GSDMD), N-terminal domain of GSDMD (NT-GSDMD) and interleukin-1β ( IL-1β) were detected by Western blot analysis. NT-GSDMD and IL-1β were also assessed by immunohistochemistry. Results?#160 Compared with those of the sham group,myocardial infarct size and fibrosis were obviously increased in the rats of the MI group. Collagen Ⅲ deposition and collagen synthesis of fibroblasts were evidently increased in myocardial tissues of the MI group compared with the sham group. The expression levels of CaSR,NLRP3,Casp-1,GSDMD,NT-GSDMD and IL-1β were significantly increased in the MI group compared with the sham group. The increased expression of NT-GSDMD and IL-1β was further confirmed by immunohistochemical staining. Moreover,Calhex231 administration inhibited all these alterations in the MI+Calhex231 group compared to the MI group. Conclusion??alhex231 reduced myocardial infarct size and fibrosis in rats,probably by inhibiti ng pyroptosis and collagen Ⅲ deposition via CaSR,which contributes to the potential clinical application of Calhex231 in myocardial fibrotic disease

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更新日期/Last Update: 2024-05-31