姜黄素调控骨髓间充质干细胞移植治疗大鼠心肌梗死的作用及机制

SUN  Hao-dan1; XU  Xin-ru1; XU  Le2; AN  Chun-yu1; WANG  Xiao-xin1; L Yang1; WANG  Hai-ping1*

doi:10.16098/j.issn.0529-1356.2026.04.009

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解剖学报 ›› 2026, Vol. 57 ›› Issue (4) : 459-466. DOI: 10.16098/j.issn.0529-1356.2026.04.009

组织学胚胎学发育生物学

姜黄素调控骨髓间充质干细胞移植治疗大鼠心肌梗死的作用及机制

孙浩丹¹徐新茹¹徐乐²安春雨¹王晓鑫¹吕洋¹王海萍^1*

作者信息 +

Effect and mechanism of curcumin on bone marrow mesenchymal stem cells transplantation in the treatment of myocardial infarction in rats

SUN Hao-dan¹, XU Xin-ru¹, XU Le², AN Chun-yu¹, WANG Xiao-xin¹, LÜ Yang¹, WANG Hai-ping^1*

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文章历史 +

摘要

目的探讨姜黄素（Cur）对骨髓间充质干细胞（BMSCs）移植治疗心肌梗死（MI）的调控，并研究其是否通过内质网应激（ERS）相关通路发挥作用。方法将40只SD大鼠随机分为假手术组(sham组)、MI模型组（MI组）、BMSCs移植组（BMSCs组）和姜黄素预处理BMSCs移植组（Cur组）。通过结扎左冠状动脉前降支建立MI模型，sham组只穿线不结扎。模型构建后，BMSCs组和Cur组分别于心肌梗死区注射未处理BMSCs或经姜黄素预处理的BMSCs。移植4周后，通过超声心动图指标评估心功能：左心室射血分数（LVEF）、左心室短轴缩短率（LVFS）、左心室舒张末期容积（LVEDV）、左心室收缩末期容积（LVESV），采用HE染色和Masson染色观察心肌组织病理变化与纤维化程度；TUNEL染色检测细胞凋亡；免疫荧光染色评估血管新生情况；Western blotting分析ERS相关蛋白：Bcl-2、Bax、活化的-Caspase (c-Casp)-3、Casp-12及葡萄糖调节蛋白-78 (GRP-78)、CCAAT/增强子结合蛋白同源蛋白（CHOP）的表达。结果与sham组相比，MI组大鼠LVEDV和LVESV显著增大（P<0.05），LVEF和LVFS明显降低（P<0.05），心肌组织排列紊乱，纤维化面积显著增加，细胞凋亡率升高，ERS相关蛋白Bax、Casp-12、CHOP、GRP-78表达上调（P<0.05），而Bcl-2表达下调（P<0.05）。与MI组相比，BMSCs移植改善了心功能并减轻心肌损伤，而Cur组的效果更明显，进一步增强LVEF和LVFS（P<0.05），下调LVEDV和LVESV（P<0.05），心肌纤维化面积和细胞凋亡率也明显下降（P<0.05），ERS通路蛋白Bax、c-Casp-3、Casp-12、CHOP、GRP-78表达均下降（P<0.05），Bcl-2表达显著升高（P<0.05）。结论姜黄素预处理可能通过抑制ERS介导的细胞凋亡通路，增强BMSCs移植在心肌梗死后的治疗作用。

Abstract

Objective To investigate the effect of curcumin (Cur) on myocardial infarction (MI) treated with by bone marrow mesenchymal stem cells (BMSCs) transplantation and to study whether it exerts its effects through endoplasmic reticulum stress (ERS)-related pathways. Methods Forty SD rats were randomly divided into sham-operated group (sham), MI model group (MI), BMSCs transplantation group (BMSCs), and curcumin-pretreated BMSCs transplantation group (Cur). An MI model was established by ligation of the left anterior descending coronary artery. In the sham group, only sutures were threaded without ligation. After modeling, untreated BMSCs or Cur-pretreated BMSCs were injected into the infarct area of the BMSCs group and the Cur group, respectively. Four weeks after transplantation, cardiac function indicators including left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV) were assessed by echocardiography. Myocardial histopathological changes and fibrosis were observed by HE staining and Masson staining. TUNEL staining was used to detect cell apoptosis. Immunofluorescence staining was used to assess angiogenesis. Western blotting was used to analyze the expression of ERS-related proteins: Bcl-2, Bax, intracellular apoptotic proteins cleaved Caspase (c-Casp)-3, Casp-12, glucose-regulated protein-78 (GRP-78), and CCAAT/enhancer-binding protein homologous protein (CHOP). Results Compared with the sham group, the MI group rats showed significantly increased LVEDV and LVESV (P<0.05), significantly decreased LVEF and LVFS (P<0.05), disordered myocardial tissue arrangement, significantly increased fibrosis area, increased apoptosis rate, and upregulated expression of ERS-related proteins Bax, c-Casp-3, Casp-12, CHOP, and GRP-78 (P<0.05), while downregulated expression of Bcl-2 (P<0.05). Compared with the MI group, BMSC transplantation improved cardiac function and reduced myocardial injury, with the Cur group showing more significant effects. It further enhanced LVEF and LVFS (P<0.05), downregulated LVEDV and LVESV (P<0.05), and significantly decreased the area of myocardial fibrosis and the rate of apoptosis (P<0.05). The expression of ERS pathway proteins Bax, c-Casp-3, Casp-12, CHOP, and GRP-78 also decreased (P<0.05), while Bcl-2 expression increased significantly (P<0.05). Conclusion Cur pretreatment may enhance the therapeutic effect of BMSC transplantation after myocardial infarction by inhibiting the ERS-mediated apoptosis pathway.

导出引用

孙浩丹徐新茹徐乐安春雨王晓鑫吕洋王海萍. 姜黄素调控骨髓间充质干细胞移植治疗大鼠心肌梗死的作用及机制[J]. 解剖学报. 2026, 57(4): 459-466 https://doi.org/10.16098/j.issn.0529-1356.2026.04.009

SUN Hao-dan , XU Xin-ru , XU Le , AN Chun-yu , WANG Xiao-xin , LÜ Yang , WANG Hai-ping.

Effect and mechanism of curcumin on bone marrow mesenchymal stem cells transplantation in the treatment of myocardial infarction in rats

[J]. Acta Anatomica Sinica. 2026, 57(4): 459-466 https://doi.org/10.16098/j.issn.0529-1356.2026.04.009

中图分类号： R329.2 R541.1

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