不同剂量乌司他丁对脓毒症心肌功能障碍小鼠的保护作用及其机制研究

doi:10.3969/j.issn.1002-1949.2019.11.016

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摘要目的探讨不同剂量乌司他丁(Ulinastatin, UTI)对脓毒症心肌功能障碍（sepsis-induced myocardial dusfunction, SIMD）小鼠的保护作用及其机制。方法 32只雄性昆明小鼠随机分为四组（n=8）：正常对照（Control）组、SIMD组、SIMD+小剂量乌司他丁（5万U/kg）（LU）组、SIMD+大剂量乌司他丁（10万U/kg）（HU）组。心脏超声观察小鼠左室射血分数（left ventricular ejection fractions, LVEF）及缩短分数（left ventricular fractional shortening, LVFS），并留取小鼠静脉血及心脏组织，苏木精-伊红染色法（hematoxylin-eosin staining, HE）观察心脏组织学改变，酶联免疫吸附法(enzyme linked immune sorbent assay, ELISA)测定血浆肌钙蛋白Ⅰ（cardiac troponin, cTnI）、肌酸激酶（creatine kinase, CK）、肿瘤坏死因子-α（tumor necrosis factor-α, TNF-α）、白细胞介素-1β（Interleukin-1β, IL-1β）水平，Western 印记法测定Toll样受体4（Toll-like receptor 4, TLR4）在心脏组织的蛋白表达。结果 SIMD组与Control组比较，LVEF、LVFS明显下降（分别为49.38±6.97 vs. 80.63±5.13, 25.13±5.44 vs. 49.25±4.27, P＜0.01），血浆cTnI（ng/mL）、CK(U/L)、TNF-α(μg/L)、IL-1β（μg/L）水平以及心脏组织TLR4蛋白表达明显升高（分别为3.66±0.61 vs. 2.75±0.33, 3480.70±714.05 vs. 1485.19±444.28, 185.57±43.73 vs. 42.15±19.06, 61.63±21.36 vs.31.57±5.49, 0.94±0.13 vs. 0.61±0.12, P＜0.01）。SIMD+HU组与SIMD组比较，LVEF、LVFS明显升高（分别为68.13±5.22 vs. 49.38±6.97, 37.38±4.21 vs. 25.13±5.44, P＜0.01），血浆cTnI、CK、TNF-α、IL-1β水平以及心脏组织TLR4蛋白表达明显下降（分别为2.91±0.39 vs. 3.66±0.61, 2309.91±575.94 vs. 3480.70±714.05, 124.73±27.18 vs. 185.57±43.73, 40.78±12.09 vs. 61.63±21.36, 0.71±0.14 vs. 0.94±0.13,P＜0.01）。SIMD+LU组与SIMD组比较，LVEF、LVFS有升高趋势，血浆cTnI、TNF-α、IL-1β水平以及心脏组织TLR4蛋白表达有下降趋势，但差异无统计学意义。Control组心脏形态学结构正常，SIMD组及SIMD+LU组可见部分心肌纤维断裂、间质水肿、细胞间隙变大、炎症细胞浸润等改变，SIMD+HU组心脏组织学改变较SIMD组好转。结论大剂量乌司他丁对SIMD小鼠具有心脏保护作用，其机制可能与乌司他丁抑制心脏组织中TLR4表达进而抑制下游炎症因子释放有关，小剂量乌司他丁效果不明显。

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关键词 ：脓毒症（sepsis）, 脓毒症心肌功能障碍（SIMD）, 乌司他丁（UTI）, Toll样受体4（TLR4）, 心脏

基金资助:河北省医学科学研究重点课题计划（20160156）

通讯作者: 胡振杰（1965-），男，博士，博士生导师，主任医师，教授，E-mail： syicu@vip.sina.com

作者简介: 陈玉红（1981-），女，博士，副主任医师，E-mail： 272409990@qq.com。

引用本文:

陈玉红，张坤，胡振杰. 不同剂量乌司他丁对脓毒症心肌功能障碍小鼠的保护作用及其机制研究[J]. 中国急救医学, 2019, 39(11): 1089-1094.
Chen Yu-hong, Zhang Kun, Hu Zhen-jie. The cardiac protective effects of Ulinastatin in different dose for sepsis-induced myocardial dysfunction mice. Chinese Journal of Critical Care Medicine, 2019, 39(11): 1089-1094.

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http://www.cnemergency.org.cn/CN/10.3969/j.issn.1002-1949.2019.11.016 或 http://www.cnemergency.org.cn/CN/Y2019/V39/I11/1089

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