乌司他丁对重症中暑小鼠心功能损害的保护作用及机制研究  

Protective effects of ulinastatin on cardiac dysfunction in mice with heat stroke and its mechanism

作　　者：吉晶晶[1,2] 李俊[2] 李慧[2] 孙学刚[3] 苏磊[2] 刘志锋[2] 

机构地区：[1]广州医科大学研究生院,广州510010 [2]广州军区广州总医院重症医学科全军热区创伤救治与组织修复重点实验室,广州510010 [3]南方医科大学中医药学院,广州510515

出　　处：《解放军医学杂志》2017年第4期290-294,共5页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金(81571940);军队"十二五"医学科研基金重点项目(BWS12J108);广东省自然科学基金团队项目(s2013030013217);广州市科技计划项目(201504281714528)~~

摘　　要：目的研究乌司他丁对重症中暑所致小鼠心功能损害的保护作用,并进一步探讨其可能机制。方法 BALB/c小鼠20只按随机数字表法分为常温+生理盐水组(Sham+NS组)、常温+乌司他丁组(Sham+UTI组)、热打击+生理盐水组(HS+NS组)、热打击+乌司他丁组(HS+UTI组)4组,每组5只。在热打击开始前腹腔注射乌司他丁10~5U/kg进行预处理。常温两组置于环境温度23.0±0.5℃条件下,热打击两组置于高温气候动物培养箱(温度36.5±0.5℃,湿度65.0%±2.0%)内,以直肠温度(T_r)达42℃作为重症中暑标准。达中暑标准后,移至常温(23.0±0.5℃)进行自然降温处理,降温6h后进行心脏超声检测,分离心肌组织,进行病理学观察,Western blotting检测总p38及磷酸化p38(p-p38)含量。结果在中暑热打击组中,HS+UTI组小鼠体温达42℃的时间较HS+NS组明显延长(P=0.044)。与Sham+NS组相比,HS+UTI组与HS+NS组动物心输出量(CO)均明显下降(P=0.017),炎症损伤评分明显升高(P<0.001),p-p38/p38比值升高(P<0.001),而HS+UTI组CO下降程度明显低于HS+NS组(P=0.030),对应的炎症损伤评分(P<0.001)及p-p38/p38比值(P=0.001)也均明显低于HS+NS组。结论重症中暑热打击可导致小鼠心肌炎性损伤和心功能障碍,而乌司他丁对重症中暑小鼠心功能具有保护作用,可能与其下调p-p38水平,减轻心肌组织炎症损伤有关。Objective To examine the effects ofulinastatin （UTI） on cardiac dysfunction in mice with heat stroke and its possible mechanism. Methods 20 mice were divided into four groups randomly： room temperature plus normal saline （Sham＋NS）, room temperature plus UTI （Sham＋UTI）, heat stress plus normal saline （HS＋NS）, heat stress plus UTI （HS＋UTI）, 5 each. 10SU/ kg UTI was delivered by intraperitoneal injection before the onset of the heat stress. Room temperature groups were housed at room temperature （23.0 ± 0.5 ℃）, while heat stress groups were kept in an incubator at 36.5 ± 0.5 ℃ and humidity of 65.0% ±2.0%. The rectal temperature （Tr） reaching 42℃ was taken as severe heat stroke, and the time in two heat stress groups was recorded. The mice were transferred to the room temperature （23.0 ±0.5 ℃） for natural cooling after the heat stroke onset. 6 hours after the treatment, cardiac output （CO） was ultrasonographically detected, the myocardium was separated for histopathological examination and the expression of total p38 and phosphorylated p38 （p-p38） was determined by Western blotting. Results The time to reach 42℃in HS＋UTI group was significantly prolonged （P=0.044）. Compared with the Sham＋NS group, the CO in HS＋NS and HS＋UTI group decreased significantly （P=0.017）, and the score of myocardial inflammation （P〈0.001） and p-p38/p38 ratio （P〈0.001） increased.The CO was significantly higher in HS＋UTI group than in HS＋NS group （P=0.030）, and the score of myocardial inflammation （P〈0.001） and p-p38/p38 ratio （P=0.001） were significantly lower. Conclusion Ulinastatin might improve the cardiac function in mice with heat stroke by decreasing the p-p38 and alleviating the inflammation response.

关 键 词：中暑 乌司他丁 心功能 炎症 

分 类 号：R594.12[医药卫生—内科学]