异源脱细胞基质心肌补片改善大鼠心肌梗死后心功能

Xenogeneic decellularized matrix myocardial patch improves cardiac function in rats with myocardial infarction

摘要

目的 探讨猪源脱细胞基质（dECM）补片对大鼠心肌梗死（MI）的治疗作用及其潜在作用机制。方法 采用物理-化学联合法制备猪源 dECM 补片。将 SD 大鼠随机分为假手术（sham）组、MI组和 MI+dECM 组，术后 4 周通过超声心动图测量左室射血分数（LVEF）、左室短轴缩短率（LVFS）和左心室收缩末期内径（LVIDs）评估其心功能，HE 和 Masson 染色观察心肌组织病理学改变，免疫荧光染色评价体内免疫反应，Western blot检测磷脂酰肌醇3—激酶/蛋白激酶 B（PI3K/Akt）通路关键蛋白表达。结果 本研究成功构建大鼠心肌梗死与 dECM补片移植模型。与 sham 组相比，MI组大鼠 LVEF、LVFS 显著降低（P<0.05），LVIDs明显增大（P<0.05），心肌纤维化程度加重，心肌梗死面积显著增加（P<0.05），p-PI3K 和 p -Akt 蛋白表达显著下调（P<0.05）。与 MI组相比，MI+dECM 组 LVEF 和 LVFS 显著增加（P<0.05），LVIDs 明显减小（P<0.05）；心肌纤维化程度减轻，心肌梗死面积减小 （P<0.05）；未见明显免疫细胞浸润；p-PI3K 和 p-Akt 蛋白表达显著上调（P<0.05）。结论 异源 dECM 补片可能通过激活 PI3K/Akt信号通路改善心肌梗死后的心功能，减少心肌纤维化，未引起明显免疫排斥反应，表现出良好的组织相容性，是一种具有临床应用前景的心肌修复材料。

Abstract

Objective To explore the therapeutic effect and underlying mechanism of a porcine-derived decellularized extracellular matrix（dECM）patch in rats with myocardial infarction（MI）. Methods Porcine cardiac dECM patches were prepared using a physico-chemical combined method.SD rats were randomly divided into sham group，MI group，and MI+dECM group.Four weeks after surgery，cardiac function was assessed by echocardiography，including left ventricular ejection fraction（LVEF），left ventricular fractional shortening（LVFS），and left ventricular internal dimension at end-systole（LVIDs）.Pathological changes of myocardial tissue were observed by hematoxylin-eosin and Masson staining.The in vivo immune response was evaluated by immunofluorescence staining and the expression of key proteins in the PI3K/Akt pathway was detected by Western blot. Results The rat models of myocardial infarction and dECM patch transplantation were successfully established.Compared with sham group，MI group had significantly decreased LVEF and LVFS（P<0.05），remarkably increased LVIDs（P<0.05），aggravated myocardial fibrosis，significantly increased myocardial infarct size（P<0.05），and notably down-regulated expression of p-PI3K and p-Akt proteins（P<0.05）.Compared with MI group，LVEF and LVFS significantly increased while LVIDs significantly reduced in MI+dECM group（all P<0.05）；the myocardial fibrosis was alleviated and myocardial infarct size reduced in MI + dECM group（P<0.05）；no obvious immune cell infiltration was observed in MI + dECM group；moreover，the expression levels of p -PI3K and p -Akt were significantly up-regulated (P<0.05). Conclusion The xenogeneic dECM patch may improve cardiac function and reduce myocardial fibrosis after myocardial infarction by activating the PI3K/Akt signaling pathway.And it does not cause obvious immune rejection，showing good tissue compatibility.These findings suggest that the xenogeneic dECM patch is a promising myocardial repair material for clinical application.

关键词

异源脱细胞基质补片 / 心肌梗死 / PI3K/Akt信号通路 / 心功能 / 心脏修复

Key words

xenogeneic dECM patch / myocardial infarction / PI3K/Akt signaling pathway / cardiac function / myocardial repair

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基金资助

博士科研启动经费资助项目(2024BS-16)