异甘草酸镁对山羊心肌缺血再灌注损伤的保护作用及机制研究Protective effect and mechanism of magnesium isoglycyrrhizinate on myocardial ischemia-reperfusion injury in goats
王铎,刘晓林,赵冀山,李晓琼,王义华,甘甜,李猛
摘要(Abstract):
目的 通过建立萨能奶山羊心肌缺血再灌注损伤冠状动脉微循环障碍模型,探讨异甘草酸镁对山羊心肌再灌注损伤的保护作用及机制。方法 将16只山羊随机分为对照组、栓塞组,异甘草酸镁低、高剂量组4组。异甘草酸镁组采用灌胃的方法,分别给予4 mg/kg、10 mg/kg异甘草酸镁、每日1次,对照组、栓塞组予以等量的0.9%生理盐水,连续灌胃7d。对照组仅行冠状动脉造影,其余3组冠状动脉造影后,球囊封堵左回旋支30 min后予以微球栓塞。模型建立72 h后检测山羊血清中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、半胱氨酸蛋白酶3(Casepase-3)、B细胞淋巴因子2(Bcl-2)、Bcl-2相关X蛋白(Bax)及白细胞介素-10(IL-10)、白细胞介素-6(IL-6)的水平。所有山羊于建模1周后采用空气栓塞法处死并取出心脏,采用苏木素-伊红和2,3,5-氯化三苯基四氮唑(TTC)染色观察梗死面积及病理变化。结果 (1)异甘草酸镁高剂量组和低剂量组较栓塞组外周血清中MDA[(2.11±0.11)nmol/ml比(3.26±0.19)nmol/ml比(4.29±0.06)nmol/ml,P<0.001]降低,GSH含量[(0.33±0.02)μmol/ml比(0.23±0.02)μmol/ml比(0.12±0.01)μmol/ml,P<0.001]升高,SOD活力[(134.78±4.24)U/ml比(123.05±5.21)U/ml比(107.57±4.28)U/ml,P<0.001]明显增加,高低剂量组间存在明显差异且呈现出剂量依赖关系(P<0.001);IL-10水平[(42.97±1.99)pg/ml比(34.35±1.78)pg/ml比(22.63±2.22)pg/ml,P<0.001]明显增加,IL-6水平[(74.94±3.50)pg/ml比(115.08±4.35)pg/ml比(152.93±5.45)pg/ml,P<0.001]则显著减少。(2)异甘草酸镁高剂量组和低剂量组较栓塞组Bcl-2[(55.10±1.24)ng/ml比(43.76±1.40)ng/ml比(30.56±2.21)ng/ml]明显增加,而Bax水平[(70.98±2.12)ng/ml比(87.96±3.10)ng/ml比(112.46±6.51)ng/ml]明显降低,Casepase-3酶活性水平[(17.67±1.05)pmol/L比(27.13±1.75)pmol/L比(39.27±1.14)pmol/L]显著下降,且与浓度呈正相关,差异均有统计学意义(均P<0.001)。(3)与栓塞组相比,异甘草酸镁组梗死面积明显缩小,组织病理学显示心肌纤维断裂、细胞水肿、坏死、中性粒细胞浸润等损伤明显减轻,且呈现出剂量依赖关系。结论 异甘草酸镁可以通过减轻山羊心肌缺血再灌注损伤中的炎症反应来维护心肌细胞膜的稳定性,保护山羊的心脏功能,从而使其可能成为心肌梗死的一种保护剂。
关键词(KeyWords): 缺血再灌注损伤;氧化应激;凋亡;异甘草酸镁
基金项目(Foundation): 内蒙古自治区自然科学基金项目(2022MS08047)
作者(Author): 王铎,刘晓林,赵冀山,李晓琼,王义华,甘甜,李猛
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