含服硝石雄黄散保护小鼠缺血心肌的实验研究
作者:
作者单位:

1.广西中医药大学,南宁 530200;2.广西中医药大学附属瑞康医院,南宁 530011;3.广西高发传染病中西医结合转化医学重点实验室,南宁 530200

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R-33


Protection of ischemic myocardium in mice by buccal administration of Xiaoshixionghuang San
Author:
Affiliation:

1.Guangxi University of Traditional Chinese Medicine, Nanning 530200, China. 2. Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine, Nanning 530011. 3. Guangxi Key Laboratory of Translational Medicine of Integrated Traditional Chinese and Western Medicine with High Infectious Diseases, Nanning 530200

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    摘要:

    目的 探索硝石雄黄散保护小鼠缺血心肌的作用机制。 方法 将 C57BL/ 6J 小鼠随机分为空白组(Blank)、假手术组(sham)、模型组(AMI)、雄黄组(XH)、硝石组(XS) 和硝石雄黄组(XSXH)。 分别在造模后第12、24 和 36 h,采用 ELISA 法检测各组血清肌钙蛋白 I( cardiac troponin I, cTnI)、肌酸激酶同工酶( creatine kinase isoenzymes, CK-MB)和乳酸脱氢酶( lactate dehydrogenase, LDH) 水平;在造模后第 14 天,采用一氧化氮( nitric oxide, NO)试剂盒检测各组血清中总 NO 的含量;采用苏木素-伊红染色法检测小鼠梗死心肌的病理损伤,经 2,3,5-氯化三苯基四氮唑染色后测定心脏梗死面积;在服用雄黄和硝石雄黄散 12 h 和第 14 天,采用相关试剂盒检测各组血清中谷丙转氨酶、碱性磷酸酶、谷草转氨酶、肌酐和尿素氮等肝肾功能指标。 结果 硝石雄黄组小鼠血清中cTnI、CK-MB 和 LDH 水平较模型组、雄黄组和硝石组显著降低(P<0. 05);假手术组血清中 NO 水平较高,发生心肌缺血后,NO 水平显著降低( P< 0. 05);与模型组比,雄黄组和硝石组能显著提高心肌梗死小鼠的 NO 水平(P<0. 01);与单味硝石或雄黄相比,硝石雄黄组 NO 含量显著升高(P<0. 001);与模型组相比,硝石雄黄组小鼠心肌梗死面积显著减小(P<0. 05);该方具有明显改善小鼠心肌病理损伤的作用。 与空白组相比,雄黄组的肝肾功能各项指标显著升高(P<0. 01),硝石雄黄组的肝肾功能指标无显著差异(P>0. 05)。 结论 在心肌缺血时,当 LArginine-eNOS-NO 通路被抑制后,硝石雄黄散可通过 NO3--NO2--NO 通路调节小鼠体内的 NO 水平,对小鼠缺血心肌起到显著的保护作用;且对小鼠的肝肾功能无明显的急性毒性和亚急性毒性影响。

    Abstract:

    Objective To explore the effect and mechanism of Xiaoshixionghuangsan in regulating NO levels to protect ischemic myocardium in mice. Methods C57BL/ 6J mice were randomly divided into Blank, sham, model (AMI), Xionghuang (XH), Xiaoshi (XS) and Xiaoshixionghuang ( XSXH) groups. Following establishment of the mouse myocardial infarction model, Blank, sham operation, and model groups were given normal saline, whereas the other groups were given corresponding intervention drugs. Serum levels of cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB), and lactate dehydrogenase ( LDH) were detected by ELISA at 12, 24 and 36 h after modeling. On the fourteenth day after modeling, total NO contents in serum were detected with an NO kit, pathological damage of the infarcted mouse myocardium was detected by hematoxylin and eosin staining, and the infarcted area was measured by 2,3,5-triphenyltetrazolium chloride staining. At 12 h and 14 days after Xiaoshixionghuang San administration, serum alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, creatinine, and urea nitrogen were detected by staining. Results Serum levels of cTnI, CK-MB and LDH in the XSXH group were significantly lower compared with AMI, XH and XS groups (P<0. 05). Serum NO levels in the sham group were high, but were significantly decreased in the AMI group (P<0. 05). Compared with the AMI group, NO levels in mice with myocardial infarction were significantly increased in XH and XS groups ( P< 0.01). Compared with single XS or XH, NO contents in the XSXH group were significantly increased ( P< 0. 001). Compared with the AMI group, myocardial infarct sizes in the XSXH group were significantly reduced (P<0. 05). In addition, the decoction markedly improved the degree of pathological damage to the myocardium in mice. Compared with the Blank group, indexes of liver and kidney function in the XH group were significantly increased (P<0. 01), and there was no significant difference in these indexes in the XSXH group (P>0. 05). Conclusions When the classical pathway L-Arginine-eNOS-NO pathway is inhibited during myocardial infarction, Xiaoshixionghuang San can regulate the level of NO in mice through the NO3--NO2--NO pathway to elicit a significant protective effect on ischemic mouse myocardium without obvious toxic effects on liver or kidney function.

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黄汕梅,李 畅,马梓珊,郭玉洪,赵洋洋,刘 原,银帮巧,刘 鹰,唐耀平.含服硝石雄黄散保护小鼠缺血心肌的实验研究[J].中国比较医学杂志,2022,32(9):19~26.

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  • 收稿日期:2022-04-06
  • 在线发布日期: 2023-01-16
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