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何涛,刘建和,杨耀闾,张杼惠,曹蛟,冯君.柴胡三参胶囊对心肌缺血再灌注损伤大鼠心脏的保护作用及铁死亡机制研究[J].湖南中医药大学学报英文版,2023,43(2):218-224.[Click to copy
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| 柴胡三参胶囊对心肌缺血再灌注损伤大鼠心脏的保护作用及铁死亡机制研究 |
| 何涛,刘建和,杨耀闾,张杼惠,曹蛟,冯君 |
| (湖南中医药大学第一附属医院, 湖南 长沙 410007;国家中医心血管病临床医学研究中心分中心, 湖南 长沙 410007) |
| 摘要: |
| 目的 研究柴胡三参胶囊对心肌缺血再灌注损伤（myocardial ischemia reperfusion injury, MIRI）大鼠心脏的保护作用。方法 取84只SPF级大鼠随机分为假手术组、模型组、地尔硫䓬组和柴胡三参胶囊低、中、高剂量组，每组14只。术前对大鼠进行灌胃，假手术组及模型组大鼠灌胃等溶剂生理盐水。假手术组只穿线不结扎，其余各组均用无菌缝合线结扎大鼠冠状动脉左前降支30 min并松线90 min构建心肌缺血再灌注模型，再灌注结束后立即取血，剥离心脏。比较各组心律失常积分，运用TTC染色法计算心肌梗死面积，运用HE染色法镜下观察心肌组织病理改变，Western blot法检测心肌组织中铁死亡相关蛋白表达水平。结果 与假手术组相比，模型组大鼠心律失常积分升高（P<0.05），心肌细胞排列紊乱，细胞核大小参差不齐，大量细胞肥大、水肿、变性，心肌梗死区域显著增加（P<0.05），铁死亡相关蛋白混合谱系激酶3（mixed lineage kinase 3, MLK3）、c-Jun氨基末端激酶（c-Jun N-terminal kinase, JNK）、肿瘤抑制蛋白p53（tumor suppressor protein p53, p53）的表达显著升高（P<0.01）。与模型组相比，柴胡三参胶囊低剂量组大鼠在心律失常积分、心肌细胞损伤改善、心肌梗死面积和铁死亡相关蛋白MLK3、JNK、p53的表达上差异无统计学意义（P>0.05）；柴胡三参胶囊中、高剂量组和地尔硫䓬组大鼠心律失常积分明显降低（P<0.05），心肌细胞损伤改善，细胞排列较整齐，水肿程度减轻，心肌梗死面积减少（P<0.05），铁死亡相关蛋白MLK3、JNK、p53的表达显著降低（P<0.01）。结论 柴胡三参胶囊中、高剂量可减轻MIRI大鼠心律失常，减少心肌梗死面积，减轻心肌病理损伤，降低铁死亡相关蛋白表达水平，其机制可能与抑制心肌铁死亡有关。 |
| 关键词: 柴胡三参胶囊 心肌缺血再灌注损伤 铁死亡 混合谱系激酶3 c-Jun氨基末端激酶 肿瘤抑制蛋白p53 |
| DOI：10.3969/j.issn.1674-070X.2023.02.007 |
| Received:May 09, 2022 |
| 基金项目:湖南省自然科学基金青年基金项目（2021JJ40419）；湖南省教育厅科学研究项目（21A034）；湖南省卫健委科研计划项目（202116001377）；湖南省中医药管理局科研课题项目（B2023019）；湖南中医药大学校级科研项目（2020XJJJ039）；湖南中医药大学研究生创新课题项目（2021CX21）。 |
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| Protective effects of Chaihu Sanshen Capsule on hearts of rats with myocardial ischemia reperfusion injury and the mechanism of ferroptosis |
| HE Tao,LIU Jianhe,YANG Yaolv,ZHANG Zhuhui,CAO Jiao,FENG Jun |
| (The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China;Sub-center of National Clinical Research Center of Cardiovascular Diseases of Chinese Medicine, Changsha, Hunan 410007, China) |
| Abstract: |
| Objective To study the protective effects of Chaihu Sanshen Capsule on hearts of rats with myocardial ischemia reperfusion injury (MIRI). Methods Eighty-four SPF rats were randomly divided into sham operation group, model group, diltiazem group, and low-, medium-, high-dose Chaihu Sanshen Capsule groups, with 14 rats in each group. The rats were given intragastric administration before operation, and the rats in sham operation group and model group received normal saline. In sham operation group, only threading was performed without ligation. In the other groups, the left anterior descending coronary artery of rats was ligated with sterile suture for 30 min and loosened for 90 min to construct the myocardial ischemia reperfusion model. After the reperfusion, blood was taken immediately and the heart was stripped. Arrhythmia scores were compared among groups, TTC staining was used to calculate the area of myocardial infarction, HE staining was taken to observe pathological changes of myocardial tissue under microscope, and Western blot was used to detect the expression level of ferroptosis-related protein in myocardial tissue. Results Compared with sham operation group, model group showed higher arrhythmias scores (P<0.05), disordered arrangement of myocardial cells, uneven sizes of nucleus, hypertrophic, edematous and degenerated cells, and the signficant increase in infarct area of myocardial tissues (P<0.05). In addition, the expression of mixed lineage kinase 3 (MLK3), c-Jun N-terminal kinase (JNK) and tumor suppressor protein p53 (p53) was significantly higher (P<0.01). While there was no significant difference between model group and low-dose Chaihu Sanshen Capsule group in arrhythmia score, improvement of myocardial cell injury, myocardial infarction area and the expression of ferroptosis-related proteins MLK3, JNK, p53 (P>0.05). Compared with model group, the medium-and high-dose Chaihu Sanshen Capsule groups and diltiazem group demonstrated significantly lower arrhythmia scores (P<0.05), improved myocardial cell damage, the neatly arranged cells, the decreased agree of edema, the less infarction area of myocardial tissues (P<0.05), and significant lower expression of ferroptosis related proteins MLK3, JNK, and p53 (P<0.01). Conclusion The medium- and high-dose Chaihu Sanshen Capsule can alleviate arrhythmia in MIRI rats, lessen myocardial infarction area, reduce myocardial pathological damage, and decrease the expression levels of ferroptosis-related proteins. The mechanism may be related to the inhibition of myocardial ferroptosis. |
| Key words: Chaihu Sanshen Capsule myocardial ischemia reperfusion injury ferroptosis mixed lineage kinase 3 c-Jun N-terminal kinase tumor suppressor protein p53 |
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