右美托咪定在LPS致大鼠心脏损伤中的保护作用及其相关机制研究

doi:10.11843/j.issn.0366-6964.2019.09.021

摘要/Abstract

摘要： 本试验旨在探究右美托咪定（DEX）对脓毒血症致大鼠心肌损伤的保护作用机制。选取体重180~220 g的健康雄性SD大鼠30只，随机均分为3组：空白对照组（CON组）、模型组（LPS组）、DEX干预组（DEX组）。LPS组和DEX组通过腹腔注射10 mg·kg^-1LPS建立脓毒血症模型，DEX组在腹腔注射LPS前30 min注射30 μg·kg^-1右美托咪定预处理；CON组腹腔注射等量灭菌生理盐水。4 h后剖杀打开腹腔，通过大鼠腹主动脉采集血液并获取心肌组织，检测血清中肌酸激酶（CK）、乳酸脱氢酶（LDH）含量；HE染色观察心肌组织病理学变化；Western blot法检测心肌组织中NOX2、NLRP3、IL-1β和IL-18表达水平。结果显示：与CON组相比，LPS组大鼠血清中CK、LDH含量极显著升高（P<0.01或P<0.001），组织病理学观察发现心肌组织损伤加重，心肌纤维间隔增宽；NOX2及下游NLRP3炎症小体相关蛋白表达量均显著或极显著（P<0.05，P<0.01或P<0.001）升高。DEX组大鼠上述指标均较LPS组显著或极显著（P<0.05，P<0.01或P<0.001）下降，并与CON组无显著差异（P>0.05）。结果表明，DEX通过降低NOX2活性，抑制NLRP3炎症小体活化，最终下调炎症因子表达量，改善大鼠脓毒血症引起的心肌损伤。

Abstract: The aim of this study was to explore the protective mechanism of dexmedetomidine (DEX) on myocardial injury induced by LPS in rats. Firstly, thirty healthy male SD rats, weighing 180-220 g, were randomly and evenly divided into three groups:control group (CON), lipopolysaccharide group (LPS) and DEX group (DEX), with 10 rats in each group. The sepsis model was established by intraperitoneal injection of 10 mg·kg^-1 LPS in rat of LPS, and DEX group; and in DEX group, the rats were pretreated with 30 μg·kg^-1 DEX 30 minutes before LPS injection. Four hours later, the abdominal cavities of rats were opened by dissection, blood samples were collected from abdominal aorta, and at the same time, myocardial tissues were obtained. Serous creatine kinase (CK) and lactic dehydrogenase (LDH) levels were measured. HE staining was used to detect myocardial pathological changes in rats. Western blot was applied to detect the expression of NOX2, NLRP3, IL-1β and IL-18 in myocardial tissue. Results were as follows:Compared with CON group, serous CK and LDH levels in LPS group increased significantly (P<0.01 or P<0.001); histopathological observation revealed that myocardial tissue injury was aggravated, and myocardial fibrous septum was widened. The expression of NOX2 and downstream NLRP3 inflammatory body-related proteins were increased significantly (P<0.05, P<0.01 or P<0.001). The above indexes in DEX group were significantly lower than those in LPS group (P<0.05, P<0.01 or P<0.001), and there was no significant difference between DEX group and CON group (P>0.05).The results showed that DEX inhibited the activation of NLRP3 inflammatory bodies by reducing the activity of NOX2. Finally, the expression of inflammatory factors was reduced to improve myocardial injury induced by sepsis in rats.

中图分类号:

S854.5

白静纯, 姚玉杰, 刘涛, 董博文, 于世明, 范宏刚. 右美托咪定在LPS致大鼠心脏损伤中的保护作用及其相关机制研究[J]. 畜牧兽医学报, 2019, 50(9): 1920-1925.

BAI Jingchun, YAO Yujie, LIU Tao, DONG Bowen, YU Shiming, FAN Honggang. Pathogenesis of Lipopolysaccharide on Rat Heart Injury and Protective Mechanism of Dexmedetomidine[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2019, 50(9): 1920-1925.

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