左西孟旦改善大鼠心肺复苏后急性肾损伤的机制研究  被引量:3

Mechanism of levosimendan on acute kidney injury after cardiopulmonary resuscitation in rats

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作  者:赵立 田磊[1] 王世伟 贾天元 杨伟强[1] 杨倩[1] 陆晓晔[1] 朱长清[1] Zhao Li;Tian Lei;Wang Shiwei;Jia Tianyuan;Yang Weiqiang;Yang Qian;Lu Xiaoye;Zhu Changqing(Department of Emergency,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200127,China)

机构地区:[1]上海交通大学医学院附属仁济医院急诊科,上海200127

出  处:《中华急诊医学杂志》2022年第1期55-60,共6页Chinese Journal of Emergency Medicine

基  金:国家自然科学基金面上项目(81971803);上海市卫生健康委员会科研项目(20184Y0126)。

摘  要:目的探索左西孟旦在改善大鼠心肺复苏后急性肾损伤中的机制。方法将25只健康成年雄性SD大鼠采用随机数字表法分为左西孟旦治疗组(治疗组, 10只)、实验组(10只)和对照组(5只)。治疗组和实验组采用窒息法建立心脏骤停-心肺复苏模型, 治疗组在复苏期间及复苏后予以左西孟旦干预, 实验组在复苏期间及复苏后予以等剂量生理盐水处理, 对照组不进行心脏骤停和心肺复苏操作, 予以等剂量生理盐水处理。复苏6 h后将3组大鼠处死, 检测大鼠血清中肌酐(serum creatinine, Scr)、尿素氮(blood urea nitrogen, Bun)、白介素-1β(interleukin-1β, IL-1β)、白介素-6(interleukin-6, IL-6)和肿瘤坏死因子α(tumor necrosis factor-α, TNF-α), HE染色观察肾脏组织损伤情况, 同时采用Paller评分量化肾脏损伤情况, TUNEL法检测凋亡, Western印迹检测磷酸化的细胞外调节蛋白激酶(phosphorylated extracellular regulated protein kinases, p-ERK)情况。正态分布计量资料多组间均数比较采用单因素方差分析, 两组间比较采用LSD-t检验。结果与对照组比较, 实验组大鼠血Scr(85.02±1.31)μmol/L、Bun(7.36±0.13)mmol/L、Paller评分(7.3±0.2)分、IL-1β(302.20±17.35)pg/mL、IL-6(564.60±23.24)pg/mL和TNF-α(1346.00±83.73)pg/mL明显高于对照组[(15.94±0.96)μmol/L、(2.95±0.18)mmol/L、(0.7±0.2)分、(7.27±0.44)pg/mL、(51.30±2.87)pg/mL、(10.39±0.52)pg/mL](均P<0.01)。与实验组相比较, 左西孟旦治疗组大鼠血Scr(63.88±2.01)μmol/L、Bun(5.45±0.47)mmol/L、Paller评分(4.8±0.2)分、IL-1β(78.61±3.66)pg/mL、IL-6(297.90±13.64)pg/mL和TNF-α(276.20±20.18)pg/mL明显降低(均P<0.01)。TUNEL染色显示, 左西孟旦能够改善肾组织细胞凋亡(P<0.01)。治疗组大鼠肾组织p-ERK蛋白表达高于实验组(P<0.01)。结论左西孟旦能够改善大鼠心肺复苏后急性肾损伤, 减轻肾组织细胞凋亡, 其机制可能与激活ERK信号通路有关。Objective To investigate the mechanism of levosimendan on acute kidney injury after cardiopulmonary resuscitation(CPR)in rats.Methods Twenty-five healthy adult male SD rats were randomly divided into three groups:control group(n=5),levosimendan group(n=10)and experimental group(n=10).A cardiac arrest-cardiopulmonary resuscitation model was established using smothering method in the experimental group and levosimendan group.The levosimendan group was treated with levosimandan during and after resuscitation,while the experimental group was given equivalent volume of saline solution during and after resuscitation,and the control group was only given equivalent volume of saline without performance of CPR.The rats in the three groups were sacrificed at 6 h after resuscitation.The serum and kidney tissue samples were collected.Serum biochemical indicators[serum creatinine(Scr),blood urea nitrogen(Bun),interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)]were measured.HE staining and Paller score were used to identify the degree of kidney damage.Apoptosis was estimated by TUNEL staining.Western blot was used to detect the expression levels of phosphorylation of extracellular regulated protein kinases(p-ERK).One-way analysis of variance was used to compare the mean values of nonnally distributed measurement data between groups.Comparisons between groups were performed using the least significant differencet test.Results Scr(85.02±1.31)μmol/L,Bun(7.36±0.13)mmol/L,Paller score(7.3±0.2),IL-1β(302.20±17.35)pg/mL,IL-6(564.60±23.24)pg/mL and TNF-α(1346±83.73)pg/mL in the experimental group were significantly higher than those of the control group[(15.94±0.96)μmol/L,(2.95±0.18)mmol/L,(0.7±0.2),(7.27±0.44)pg/mL,(51.30±2.87)pg/mL,and(10.39±0.52)pg/mL](all P<0.01).Compared with the experimental group,Scr(63.88±2.01)μmol/L,Bun(5.45±0.47)mmol/L,paller score(4.8±0.2),IL-1β(78.61±3.66)pg/mL,IL-6(297.90±13.64)pg/mL and TNF-α(276.2±20.18)pg/mL were significantly decreased in the levosi

关 键 词:心脏骤停 心肺复苏 急性肾损伤 左西孟旦 细胞外调节蛋白激酶 

分 类 号:R459.7[医药卫生—急诊医学] R692[医药卫生—治疗学]

 

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