甲泼尼龙减轻大鼠呼吸机相关性肺损伤机制与p38 MAPK/NLRP3通路的关系  

Relationship between mechanism underlying methylprednisolone-induced alleviation of ventilator-induced lung injury and p38MAPK/NLRP3 pathway in lung tissues of rats

作　　者：姚忠岩[1] 瞿敏[1] 孙文波[1] 娄宁 陈鹏[1] 孙秀伟[1] 黄冬冬[2] Yao Zhongyan;Qu Min;Sun Wenbo;Lou Ning;Chen Peng;Sun Xiuwei;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,061001 [2]沧州医学高等专科学校医学系诊断教研室,061001

出　　处：《中华麻醉学杂志》2021年第12期1528-1531,共4页Chinese Journal of Anesthesiology

摘　　要：目的评价甲泼尼龙减轻大鼠呼吸机相关性肺损伤(VILI)机制与p38丝裂原活化蛋白激酶(p38 MAPK)/核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)通路的关系。方法清洁级雄性SD大鼠60只,体重270~320 g,4~5月龄,采用随机数字表法分为3组(n=20):对照组(C组)、机械通气组(V组)和甲泼尼龙组(M组)。C组不行机械通气,自主呼吸空气4 h;V组机械通气(RR 40次/min,V_(T)40 ml/kg,I∶E 1∶1,PEEP 0,FiO221%)4 h;M组机械通气前20 min静脉注射甲泼尼龙10 mg/kg。机械通气4 h时,收集肺泡支气管灌洗液(BALF)和肺组织,测定BALF IL-1β、IL-18、TNF-α浓度与肺湿重/干重(W/D)比值,观察肺组织病理学结果。Western blot法检测肺组织p38 MAPK、磷酸化p38 MAPK(p-p38 MAPK)、NLRP3、凋亡相关斑点样蛋白(ASC)、天门冬氨酸特异性半胱氨酸蛋白酶-1(caspase-1)的表达水平。结果与C组比较,V组肺组织W/D比值、BALF IL-1β、IL-18和TNF-α浓度升高,p-p38MAPK、NLRP3、ASC和caspase-1表达上调(P<0.05),M组差异无统计学意义(P>0.05);与V组比较,M组肺组织W/D比值、BALF IL-1β、IL-18和TNF-α浓度降低,p-p38MAPK、NLRP3、ASC和caspase-1表达下调(P<0.05)。结论甲泼尼龙减轻大鼠VILI的机制可能与抑制p38MAPK/NLRP3通路活性,减轻肺组织炎症反应有关。Objective To evaluate the relationship between the mechanism underlying methylprednisolone-induced alleviation of ventilator-induced lung injury(VILI)and p38 mitogen-activated protein kinase(p38 MAPK)/nucleotide binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)pathway in lung tissues of rats.Methods Sixty clean-grade male Sprague-Dawley rats,weighing 270-320 g,aged 4-5 months,were divided into 3 groups(n=20 each)using a random number table method:control group(group C),mechanical ventilation group(group V),and methylprednisolone group(group M).Group C breathed air spontaneously for 4 h without mechanical ventilation.Group V was mechanically ventilated(RR 40 times/min,V_(T) 40 ml/kg,I∶E 1∶1,PEEP 0,FiO221%)for 4 h.Group M received intravenous methylprednisolone 10 mg/kg at 20 min before mechanical ventilation.At 4 h of mechanical ventilation,broncho-alveolar lavage fluid(BALF)was collected to measure the concentrations of interleukin-1beta(IL-1β),IL-18,and tumor necrosis factor-alpha(TNF-α)and wet/dry lung weight ratio(W/D ratio),and lung tissues were obtained for microscopic examination of the histopathological changes and for detection of the expression of p38MAPK,phosphorylated p38MAPK(p-p38MAPK),NLRP3,apoptosis-related speck-like protein containing a CARD(ASC),and cysteinyl aspartate-specific protease-1(caspase-1)(using Western blot).Results Compared with group C,the W/D ratio of lung tissues and concentrations IL-1β,IL-18 and TNF-α in BALF were significantly increased,and the expression of p-p38MAPK,NLRP3,ASC and caspase-1 was up-regulated in group V(P<0.05),and no significant change was found in group M(P>0.05).Compared with group V,the W/D ratio of lung tissues and concentrations of IL-1β,IL-18 and TNF-α in BALF were significantly decreased,and the expression of p-p38MAPK,NLRP3,ASC and caspase-1 was down-regulated in group M(P<0.05).Conclusion The mechanism by which methylprednisolone alleviates VILI may be related to inhibition of p38MAPK/NLRP3 pathway activity and reduction of in

关 键 词：甲泼尼龙 呼吸机相关性肺损伤 NLR家族 热蛋白结构域包含蛋白3 P38丝裂原活化蛋白激酶类 

分 类 号：R614[医药卫生—麻醉学]