1.湖南中医药大学中医诊断研究所,湖南省长沙市岳麓区含浦科教园学士路300号,410208
2.湖南中医药大学中医学院
3.上海中医药大学附属龙华医院
4.湖南中医药大学第一附属医院
5.湖南中医药大学医学院
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收稿:2022-08-26,
修回:2023-04-04,
纸质出版:2023-06-17
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于子璇,张书萌,张梦雪等.养心通脉方对心肌梗死血瘀证模型大鼠心肌能量代谢的影响[J].中医杂志,2023,64(12):1255-1262.
YU Zixuan,ZHANG Shumeng,ZHANG Mengxue,et al.Effects of Yangxin Tongmai Formula (养心通脉方) on Myocardial Energy Metabolism in Myocardial Infarction Model Rats with Blood Stasis Syndrome[J].Journal of Traditional Chinese Medicine,2023,64(12):1255-1262.
于子璇,张书萌,张梦雪等.养心通脉方对心肌梗死血瘀证模型大鼠心肌能量代谢的影响[J].中医杂志,2023,64(12):1255-1262. DOI: 10.13288/j.11-2166/r.2023.12.012.
YU Zixuan,ZHANG Shumeng,ZHANG Mengxue,et al.Effects of Yangxin Tongmai Formula (养心通脉方) on Myocardial Energy Metabolism in Myocardial Infarction Model Rats with Blood Stasis Syndrome[J].Journal of Traditional Chinese Medicine,2023,64(12):1255-1262. DOI: 10.13288/j.11-2166/r.2023.12.012.
目的
2
探讨养心通脉方治疗心肌梗死血瘀证的可能作用机制。
方法
2
50只大鼠随机选取38只在高脂饲料喂养下运用维生素D3灌胃+异丙肾上腺素腹部皮下注射的方法建立心肌梗死血瘀证模型。从造模成功的28只大鼠中选出24只随机分为模型组、养心通脉方组和阿托伐他汀钙组,每组8只,未进行造模的大鼠中8只作为空白组。养心通脉方组大鼠给予养心通脉方12 g/(kg·d)灌胃,阿托伐他汀钙组大鼠给予阿托伐他汀钙片1.8 mg/(kg·d)灌胃,空白组和模型组给予4 ml/(kg·d)蒸馏水灌胃,各组均每天1次,连续14天。HE染色法观察冠状动脉病理形态学改变,透射电镜观察心肌组织线粒体超微结构及数量变化,ELISA法检测心肌组织腺嘌呤核苷三磷酸(ATP)、血清一氧化氮(NO)与C1q肿瘤坏死因子相关蛋白3(CTRP3)水平,Western blot法测定心肌组织CTRP3蛋白表达水平。
结果
2
与空白组相比,模型组冠状动脉组织出现内膜增厚、内皮破损、炎性浸润等改变;心肌线粒体数量减少,膜结构变浅,部分破溃;心肌组织ATP、血清NO水平明显降低,心肌组织CTRP3蛋白表达及血清CTRP3水平明显下降(
P
<0.05)。与模型组比较,养心通脉方组和阿托伐他汀钙组冠状动脉内皮损伤情况均明显改善,心肌组织肌小节排列规律,心肌线粒体数量增加、结构完整,心肌组织ATP含量、血清NO含量显著升高,心肌组织CTRP3蛋白表达及血清CTRP3水平明显升高(
P
<0.05)。与养心通脉方组比较,阿托伐他汀钙组冠状动脉内皮损伤以及线粒体膜结构破坏成程度均较为明显,心肌组织ATP及CTRP3蛋白表达水平、血清CTRP3水平均明显升高(
P
<0.05)。
结论
2
养心通脉方能够显著改善心肌梗死血瘀证大鼠的心肌线粒体能量代谢功能,抵抗冠状动脉内皮损伤,其机制可能与升高脂肪因子CTRP3含量相关。
Objective
2
To explore the potential mechanism of
Yangxin Tongmai Formula
(养心通脉方, YXTM) in the treatment of myocardial infarction (MI) with blood stasis syndrome (BSS).
Methods
2
A total of 50 rats were selected, and 38 of them were randomly selected and fed with high fat diet, using intragastric administration of vitamin D3 plus intraperitoneal injection of isoproterenol to establish the MI rat model with BSS. Twenty-four out of the 28 successfully modeled rats were randomly divided into model group, YXTM group and atorvastatin calcium group, with eight rats in each group. Eight healthy rats were selected as blank group. The YXTM group and atorvastatin calcium group were given 12 g/(kg·d) of YXTM and 1.8 mg/(kg·d) of atorvastatin calcium tablets by gavage, respectively, while the blank group and the model group were administered with 4 ml/(kg·d) of distilled water by gavage. Each group was treated once a day for 14 consecutive days. The pathological changes of coronary arteries were observed by hematoxylin and eosin (HE) staining. The number and morphology of mitochondria in myocardial tissues were observed by transmission electron microscopy. The levels of adenosine triphosphate (ATP) in myocardial tissue, serum nitric oxide (NO) and C1q tumor necrosis factor-related protein 3 (CTRP3) were detected by ELISA kit. The expression of CTRP3 protein in myocardial tissue was determined by Western blot.
Results
2
Compared to the blank group, the model group showed intimal thickening, endothelial damage, inflammatory infiltration and other changes; the number of myocardial mitochondria in the model group decreased, and the membrane structure became shallower, and even ruptured, with decreased ATP in myocardial tissue, serum NO level, CTRP3 protein expression in myocardial tissue, and serum CTRP3 level (
P
<0.05). Compared to those in the model group, the coronary endothelial injury was significantly improved in the YXTM group and atorvastatin calcium group, and the arrangement of sarcomeres in myocardial tissue was regular, with increased number of myocardial mitochondria, complete structure of myocardial mitochondria, and increased content of ATP in myocardial tissue, serum NO level, CTRP3 protein expression in myocardial tissue, and serum CTRP3 level (
P
<0.05). Compared to those in the YXTM group, the coronary artery endothelial injury and mitochondrial membrane structure damage were more severe in the atorvastatin calcium group, and the ATP level and CTRP3 protein expression level in myocardial tissue and serum level of CTRP3 significantly increased (
P
<0.05).
Conclusion
2
YXTM can significantly improve myocardial mitochondrial energy metabolism and resist endothelial injury in rats with MI and BSS, and its mechanism may be related to the increase of adipokines CTRP3 content.
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