右美托咪定对VILI大鼠肺泡上皮屏障功能的影响及PKC在其中的作用  

Effects of dexmedetomidine on alveolar epithelial barrier function in rats with VILI and the role of PKC

作　　者：瞿敏[1] 孙文波[1] 姚忠岩[1] 焦翠丽 张秀青 李书花[1] 黄冬冬[2] Qu Min;Sun Wenbo;Yao Zhongyan;Jiao Cuili;Zhang Xiuqing;Li Shuhua;Huang Dongdong(Department of Anesthesiology,Cangzhou Center Hospital,Cangzhou 061001,China;Department of Medical Diagnosis,Cangzhou Medical College,Cangzhou 061001,China)

机构地区：[1]沧州市中心医院麻醉科,沧州061001 [2]沧州医学高等专科学校医学诊断教研室,沧州061001

出　　处：《中华麻醉学杂志》2022年第6期695-699,共5页Chinese Journal of Anesthesiology

摘　　要：目的评价右美托咪定对呼吸机相关性肺损伤(VILI)大鼠肺泡上皮屏障功能的影响及蛋白激酶C(PKC)在其中的作用。方法清洁级雄性SD大鼠100只,体重270~320 g,4~5月龄,采用随机数字表法分为5组(n=20):对照组(C组)、VILI组(V组)、PKC抑制剂组(B组)、右美托咪定组(D组)和右美托咪定+PKC激动剂组(DP组)。采用潮气量40 ml/kg机械通气4 h的方法制备VILI模型。B组于机械通气前1 h肌肉注射PKC抑制剂双吲哚马来酰亚胺Ⅰ0.12 mg/kg;D组和DP组于机械通气前20 min静脉注射右美托咪定5.0μg/kg,机械通气期间以5.0μg·kg^(-1)·h^(-1)的速率静脉泵注;DP组于机械通气前30 min腹腔注射PKC激动剂佛波醇-12-肉豆蔻酸-13-乙酸酯15μg/kg。机械通气4 h时,测定氧合指数(OI)、肺通透指数(LPI)、肺湿重/干重(W/D)比值,观察肺组织病理学结果,行肺损伤评分。采用Western blot法和RT-PCR法分别检测肺组织PKC、occludin、ZO-1及其mRNA的表达水平。结果与C组比较,V组和DP组OI降低,LPI、W/D比值和肺损伤评分升高,PKC及其mRNA表达上调,occludin和ZO-1及其mRNA表达下调(P<0.05),B组与D组上述指标差异无统计学意义(P>0.05);与V组比较,B组、D组和DP组OI升高,LPI、W/D比值和肺损伤评分降低,PKC及其mRNA表达下调,occludin和ZO-1及其mRNA表达上调(P<0.05);与D组比较,DP组OI降低,LPI、W/D比值和肺损伤评分升高,PKC及其mRNA表达上调,occludin和ZO-1及其mRNA表达下调(P<0.05)。结论右美托咪定可减轻VILI大鼠肺泡上皮屏障功能损伤,其机制与抑制PKC激活,上调occludin和ZO-1表达有关。Objective To evaluate the effects of dexmedetomidine on alveolar epithelial barrier function in rats with ventilator-induced lung injury(VILI),and the role of protein kinase C(PKC).Methods One hundred clean-grade male Sprague-Dawley rats,weighing 270-320 g,aged 4-5 months,were divided into 5 groups(n=20 each)using a random number table method:control group(group C),VILI group(group V),PKC inhibitor group(group B),dexmedetomidine group(group D),and dexmedetomidine plus PKC agonist group(DP group).The VILI model was developed by mechanical ventilation with a tidal volume of 40 ml/kg for 4 h in anesthetized animals.Group C breathed air autonomously for 4 h without mechanical ventilation.Group V was mechanically ventilated for 4 h.In group B,bisindolvlmaleimide I 0.12 mg/kg was injected intramuscularly 1 h before mechanical ventilation.In D and DP groups,dxmedetomidine 5.0μg/kg was injected intravenously at 20 min before mechanical ventilation,and dexmedetomidine was intravenously infused at the rate of 5.0μg·kg^(-1)·h^(-1) during mechanical ventilation.In group DP,PKC agonist phorbol-12-myristic acid-13-acetate 15μg/kg was intraperitoneally injected at 30 min before mechanical ventilation.At 4 h of mechanical ventilation,oxygenation index(OI),lung permeability index(LPI)and wet/dry lung weight(W/D)ratio were measured,the pathological changes of lung tissues were observed,and lung injury was assessed and scored.The expression of PKC,occludin and ZO-1 protein was detected by Western blot,and the expression of PKC mRNA,occludin mRNA and ZO-1 mRNA was determined by real-time polymerase chain reaction.Results Compared with group C,OI was significantly decreased,LPI,W/D ratio and lung injury score were increased,the expression of PKC protein and mRNA was up-regulated,and the expression of occludin and ZO-1 protein and mRNA was down-regulated in V and DP groups(P<0.05),and no significant change was found in the parameters mentioned above in B and D groups(P>0.05).Compared with group V,OI was significantly increased,LP

关 键 词：右美托咪啶 呼吸机相关性肺损伤 肺泡 上皮 蛋白激酶C 

分 类 号：R614[医药卫生—麻醉学]