右美托咪定对机械通气相关性肺损伤大鼠肺组织细胞凋亡的影响  

Effects of dexmedetomidine on cell apoptosis in lung tissue in a rat model of ventilator - induced lung injury

作　　者：瞿敏[1] 茅顺洪 缴宝杰[1] 刘香阁[1] 杨强[1] 史丹丹[2] 马志红 李慧智 Qu Min , Mao Shun - hong , Jiao Bao -jie, Liu Xiang - ge , Yang Qiang , Shi Dan - dan, Ma Zhi -hong, Li Hui -zhi.(The Second Department of Anesthesiology, Cangzhou Center Hospital, Cangzhou 061001, Chin)

机构地区：[1]沧州市中心医院麻醉二科,河北沧州061001 [2]沧州市中心医院产二科,河北沧州061001 [3]沧州市人民医院颐和妇产,河北沧州361000 [4]泊头市医院麻醉科,河北泊头062150

出　　处：《中国急救医学》2018年第3期250-255,I0003,共7页Chinese Journal of Critical Care Medicine

摘　　要：目的 探讨右美托咪定（DEX）对机械通气相关性肺损伤大鼠肺组织细胞凋亡的影响。方法 清洁级雄性SD大鼠100只，采用随机数字表法将大鼠分为五组（每组n=20）：对照组（C组）、机械通气组（V组）和不同剂量右美托咪定组（DEX 1～3组）。机械通气参数设置：潮气量 40 mL/kg，呼吸频率 50次/min，吸呼比 1∶1,FiO2 21％。DEX 1～3组机械通气前20 min分别静脉输注DEX 0.5、2.5、5.0 μg/kg，机械通气期间DEX分别以0.5、2.5、5.0 μg/（kg·h）的速率静脉输注4 h。于插管即刻及机械通气1、2和4 h时采集股动脉血样，进行动脉血气分析，并记录PaO2，计算氧合指数（OI）。机械通气4 h时处死大鼠，回收肺泡支气管灌洗液（BALF），测定肺通透指数（LPI），取左肺下叶,测定肺湿/干质量（W/D）比值。采用Western blot法检测JNK、p-JNK、Bax、Bcl-2、 Caspase-3和唯BH3结构域促凋亡因子（BID、BIM）的表达水平。采用RT-PCR法检测JNK mRNA的表达。光镜下，观察肺组织病理学结果，测定肺泡损伤率（IAR），采用TUNEL法观察肺组织细胞凋亡情况并计算凋亡指数。结果 与C组比较，V组和DEX 1组OI降低，W/D比值、LPI、IAR（%）、AI（%）升高，p-JNK和JNK mRNA表达上调，促凋亡因子BID、BIM的表达增加，同时伴有Bax 表达增加，Bcl-2表达减少，Caspase-3表达增加（P＜0.05），DEX 2、3组上述指标差异无统计学意义（P＞0.05）；与V组比较，DEX 2、3组OI升高，W/D比值、LPI、IAR（%）、AI（%）降低，p-JNK和JNK mRNA表达下调，促凋亡因子BID、BIM表达减少，同时伴有Bax表达减少，Bcl-2表达增加，Caspase-3表达减少（P＜0.05），DEX 1组上述指标差异无统计学意义（P＞0.05）。与V组比较,DEX 2、3组肺组织病理损伤减轻，TUNEL法检测细胞凋亡减少。结论 DEX可减轻大鼠机械通气相关性肺损伤，与其抑制肺组织JNK磷酸化，下调唯BH3结构域Objective To investigate the effect of dexmedetomidine （DEX）on the apoptosis of lung tissue in a rat model of ventilator - induced lung injury. Methods One hundred pathogen - free male Sprague -Dawley rats, were randomly （random number） divided into 5 groups （n = 20 each） ： the control group （group C）, mechanical ventilation group （group V） and different dexmedetomidine doses of groups （DEX 1 - 3 group ）. Mechanical ventilation parameters： moisture content of 40 mL/kg, respiratory rate 50 breaths/min, I ： E ratio 1 ： 1, FiO2 is 21%. In DEX 1 -3 groups： dexmedetomidine 0.5, 2.5, and 5.0μg/kg were infused intravenously, respectively, over 20 min before ventilation, and then dexmedetomidine were infused intravenously for 4 h at a rate of 0.5, 2.5, and 5.0 μg/（ kg .h）, respectively, during mechanical ventilation. Immediately before tracheal intubation and at 1,2 and 4 h of ventilation,blood samples were collected from the femoral artery for blood gas analysis, the PaO2 was recorded, and oxygen index was calculated. At 4 h of mechanical ventilation, the rats were sacrificed. Bronchial alveolar lavage fluid （BALF） was recycled to determine the lung permeability index （LPI）, and the left lobe of the lungs was removed to determine the ratio of pulmonary wet/dry weight （ W/D）, and to detect of the expression of JNK, p - JNK, Bax, Bcl - 2, Caspase - 3 and BH3 - only domain pro - apoptotic factor （ BID, BIM） by Western blot. The expression of JNK mRNA was detected by RT- PCR. The pathological changes of lung tissues were observed under light microscope, and the alveolar injury rate （IAR） was determined. The lung cell apoptosis was observed and apoptosis index was calculated by TUNEL method. Results Compared with the group C, group V and group DEX 10I decreased, W/D ratio, LPI, IAR, AI and the expression of BID, BIM increased, p - JNK and JNK mRNA were up - regulated, accompanied by increased expression of Bax, Caspase - 3 , and decreased expression of Bcl - 2 （ P

关 键 词：右美托咪啶(DEX) 细胞凋亡 JNK丝裂原活化蛋白激酶类 唯BH3结构域促凋亡因子 

分 类 号：R605.973[医药卫生—急诊医学]