热休克蛋白70对中暑大鼠急性肺损伤的保护作用及机制研究  

Protective effects of heat shock protein 70 on the acute lung injury of rats with heat stroke and its mechanism

作　　者：耿焱[1] 彭娜[2] 童华生[2] 潘志国[2] 刘云松[2] 马强[3] 苏磊[2] 

机构地区：[1]解放军303医院重症医学科,南宁530021 [2]广州军区广州总医院重症医学科,广州510010 [3]南方医科大学抗体工程研究所,广州510515

出　　处：《解放军医学杂志》2017年第4期295-300,共6页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金(81671896,81471839);中国博士后科学基金(2012M512181);广西省自然科学基金(2016GXNSFAA380313);广东省自然科学基金(2016A030310288,2014A030313601);广东省科技计划项目(2013B031800010)~~

摘　　要：目的观察热休克蛋白70(HSP70)对急性肺损伤的保护作用。方法 64只SD大鼠按随机数字表法分为假加热正常对照组(Sham组)、中暑组(HS组)、中暑加谷氨酰胺处理组(HS+GLN组)和中暑加槲皮素处理组(HS+QU组),每组16只。Sham组大鼠置于温度23℃,湿度55%±5%环境中,其余3组大鼠置于模拟热气候动物舱(舱内温度39℃,相对湿度65%)内。监测大鼠直肠温度、收缩压和脉率,比较各组大鼠热应激反应的差异。以收缩压从峰值开始下降作为中暑的开始,之后将大鼠移至常温复温。分别在中暑恢复期0h和6h处死大鼠,每个时间点8只,留取支气管肺泡灌洗液(BALF)后分离肺脏组织行组织学观察。采用酶联免疫法检测BALF中的IL-1β、TNF-α和IL-6浓度,以及肺组织匀浆中的HSP70浓度。结果与HS组和HS+QU大鼠比较,HS+GLN组大鼠承受更多的热负荷后才发生HS(P<0.001),起病后的中位生存时间明显延长(P<0.001)。与Sham组比较,HS组大鼠肺组织匀浆HSP70浓度呈时间依赖性升高(P<0.001);HS+GLN组HSP70浓度在各个时点与HS组比较均明显升高(P<0.001),而HS+QU组的HSP70表达则受到明显抑制时点与Sham组比较差异无统计学意义(P>0.05),但明显低于HS组和HS+GLN组(P<0.001)。与HS组和HS+QU组比较,HS+GLN组大鼠BALF中的IL-1β、TNF-α和IL-6浓度明显降低(P<0.001),病理结果显示其肺损伤更轻(P<0.001),而HS+QU组则相反。结论 HSP70具有保护HS大鼠急性肺损伤的作用,其机制可能与增强大鼠热耐受能力和抑制HS大鼠肺部炎症相关。Objective To investigate the protective effect of heat shock protein （HSP） 70 on the acute lung injury （ALI） of rats with heat stroke. Methods Sixty four rats were randomly （by employing a random number table） assigned into a sham-heated group （Sham group）, heat stress group （HS group）, and HS plus gluttamine treatment group （HS＋GLN group） and HS plus quercet in treatment group （HS＋O.U group）, 16 each. All rats were housed in a artificial climate chamber, with the rats in the sham groups exposed to a temperature of 23 ℃ and humidity of 55% ± 5%, while the rats of HS, HS＋GLN and HS＋QU groups to an ambient temperature of 39 ℃ and humidity of 65%. During heat stress or sham heating, rectal temperature （Tr）, systolic blood pressure （SBP） and pulse rate （PR） were monitored to observe the difference in heat stress response among the groups. The time point at which the SBP started to drop from the peak level was taken as the point of HS onset. At the onset of HS, heat exposure was terminated, then the rats were immediately removed from the chamber, and returned to room temperature. The rats were scarified Oh and 6h after HSonset respectively. After bronchoalveolar lavage fluid （BALF） was collected, the lungs of all animals were harvested for pathological examination of lung injury. The concentrations of IL-1β, TNF-α and IL-6 in BALF and HSP70 in Lung homogenate were measured by using an enzyme linked immunosorbent assay kit. Results Compared with HS and HS＋Q_U groups, the rats in HS＋GLN group required significantly greater heat load to induce HS （P〈0.001）, and had longer survival time span after HS onset. Compared with Sham group, the concentration of HSP70 in lung homogenate in HS group increased in a time-dependent manner （P〈0.001）. In comparison with HS group, the concentration of HSP70 in lung homogenate from HS＋GLN group was significantly elevated at each time point （P〈0.001）, while the treatment with QU significantly inhibited the e

关 键 词：中暑 HSP70热休克蛋白质类 肺损伤 

分 类 号：R594.12[医药卫生—内科学]