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覃浩昌, 杨漾, 张慧卿, 郑淋淋, 李扬, 余嗣澳, 陈聪, 廖菁.芎芪方调控氧化三甲胺对心肌缺血再灌注损伤的影响[J].湖南中医药大学学报英文版,2025,45(5):803-809.[Click to copy
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| 芎芪方调控氧化三甲胺对心肌缺血再灌注损伤的影响 |
| 覃浩昌,杨漾,张慧卿,郑淋淋,李扬,余嗣澳,陈聪,廖菁 |
| (湖南中医药大学, 湖南 长沙 410208;湖南中医药大学第一附属医院, 湖南 长沙 410007) |
| 摘要: |
| 目的 基于“心与小肠相表里”芎芪方调控氧化三甲胺（TMAO）保护心肌缺血再灌注损伤（MIRI）的作用机制。方法 将50只雄性SD大鼠随机分为假手术组、模型组、芎芪方组、3,3-二甲基-1-丁醇（DMB）组、芎芪方+DMB组，每组10只。各给药组给予相应药物干预，假手术组、模型组给予等体积生理盐水，每天1次连续灌胃14 d。通过结扎大鼠冠状动脉左前降支的方法建立MIRI大鼠模型。造模结束后，腹主动脉取血，HE染色观察心肌及空肠组织病理改变；ELISA法检测大鼠血清肌酸激酶同工酶MB（CK-MB）、乳酸脱氢酶（LDH）、丙二醛（MDA）、超氧化物歧化酶（SOD）、白细胞介素（IL）-1β、IL-6；三重四极液相色谱-质谱联用技术检测大鼠血清TMAO水平。结果 与假手术组比较，模型组大鼠心肌与空肠组织形态出现心肌纤维断裂、炎性浸润及空肠绒毛肿胀、断裂等病理损伤，血清CK-MB、LDH、MDA、IL-1β、IL-6及TMAO水平均升高（P＜0.05），而SOD活性降低（P＜0.05）。与模型组比较，芎芪方组、DMB组、芎芪方+DMB组心肌及空肠组织损伤程度均有改善，血清CK-MB、LDH、MDA、IL-1β、IL-6、TMAO水平降低（P＜0.05），SOD活性升高（P＜0.05）。与芎芪方组相比，DMB组大鼠心肌纤维断裂、心肌细胞变形、组织空泡增多的情况较严重，血清CK-MB、LDH、MDA、IL-1β、TMAO水平明显升高（P＜0.05），SOD活性明显降低（P＜0.05）芎芪方+DMB组大鼠心肌组织细胞轻微溶解，有少量炎症细胞浸润，细胞间隙变大，血清CK-MB、LDH、MDA、IL-1β水平明显升高（P＜0.05）。与DMB组相比，芎芪方+DMB组心肌纤维溶解、炎性浸润减轻，但空肠绒毛肿胀加剧，血清CK-MB、LDH、MDA、IL-1β、IL-6、TMAO水平降低（P＜0.05），SOD活性显著升高（P＜0.05）。结论 “心与小肠相表里”是现代医学从肠论治MIRI患者的重要科学依据，芎芪方可能通过调控TMAO介导的炎症信号通路，减轻氧化应激及炎症级联反应，从而在MIRI应激事件中对缺血再灌注心肌发挥预防性保护作用。 |
| 关键词: 心肌缺血再灌注损伤 心与小肠相表里 氧化三甲胺 川芎 黄芪 |
| DOI：10.3969/j.issn.1674-070X.2025.05.004 |
| Received:March 10, 2025 |
| 基金项目:国家自然科学基金项目（81704065）；湖南省自然科学基金项目（2023JJ30455，2025JJ60804）；湖南省教育厅科学研究项目（22A0274，23C0172）；湖南省中医药科研计划项目（A2023030，B2023022）；湖南中医药大学研究生创新项目（2023CX172）；湖南中医药大学平台开放基金项目（2022FPKFJJ04）。 |
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| Effects of Xiongqi Formula on myocardial ischemia-reperfusion injury by regulating trimethylamine N-oxide |
| QIN Haochang, YANG Yang, ZHANG Huiqing, ZHENG Linlin, LI Yang, YU Si'ao, CHEN Cong, LIAO Jing |
| (Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China) |
| Abstract: |
| Objective To explore the mechanism of action of Xiongqi Formula (XQF) in regulating trimethylamine N-oxide (TMAO) to protect against myocardial ischemia-reperfusion injury (MIRI) based on "the heart and small intestine being exteriorly and interiorly related to each other". Methods Fifty male Sprague-Dawley rats were randomly divided into five groups (10 rats per group): sham-operated, model, XQF 3,3-dimethyl-1-butanol (DMB), and XQF+DMB. The sham-operated and model groups received an equivalent volume of saline. All groups underwent intragastric administration for 14 consecutive days. The MIRI model was established by ligating the rat left anterior descending coronary artery. After modeling, blood was collected from the rat abdominal aorta. HE staining was used to observe histopathological changes in the rat myocardial and jejunal tissues. ELISA was used to determine serum creatine kinase isoenzyme MB (CK-MB), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), interleukin (IL)-1β, and IL-6 in rats. Triple quadrupole liquid chromatography-mass spectrometry was used to measure serum TMAO levels in rats. Results Compared with the sham-operated group, the rat myocardial and jejunal tissues in the model group showed pathological damage such as myocardial fiber rupture, inflammatory infiltration, and jejunal villus swelling and rupture. The serum levels of CK-MB, LDH, MDA, IL-1β, IL-6, and TMAO significantly increased (P<0.05), while the SOD activity decreased (P<0.05). Compared with the model group, the XQF, DMB, and XQF+DMB groups showed attenuated myocardial and jejunal damage, with reduced serum CK-MB, LDH, MDA, IL-1β, IL-6, and TMAO levels (P<0.05) and increased SOD activity (P<0.05). Compared with the XQF group, the DMB group displayed more severe myocardial fiber rupture, cardiomyocyte deformation, vacuolization, elevated serum CK-MB, LDH, MDA, IL-1β, and TMAO levels (P<0.05), and reduced SOD activity (P<0.05). The XQF + DMB group showed mild myocardial cell dissolution, slight inflammatory infiltration, widened intercellular spaces, and increased CK-MB, LDH, MDA, and IL-1β levels (P<0.05). Compared with the DMB group, myocardial fiber dissolution and inflammatory infiltration in the XQF+DMB group were alleviated but jejunal villus swelling was aggravated; the serum CK-MB, LDH, MDA, IL-1β, IL-6, and TMAO levels decreased (P<0.05), while the SOD activity increased (P<0.05). Conclusion "The heart and small intestine being exteriorly and interiorly related to each other" is an important scientific basis for modern medicine to treat MIRI from the perspective of the intestine. XQF may exert a preventive protective effect against myocardial ischemia-reperfusion in MIRI stress events by regulating the TMAO-mediated inflammatory signaling pathway and thereby alleviating oxidative stress and inflammatory cascade. |
| Key words: myocardial ischemia-reperfusion injury the heart and small intestine being exteriorly and interiorly related to each other trimethylamine N-oxide Chuanxiong (Chuanxiong Rhizoma) Huangqi (Astragali Radix) |
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