摘要
目的评价右美托咪对体外循环(CPB)大鼠肺组织Janus激酶2/信号转导子和转录激活子3(JAK2/STAT3)信号通路的影响。方法清洁级健康成年雄性SD大鼠24只,体重320~350 g,12~16周龄,采用随机数字表法分为3组(n=8):假手术组(S组)、CPB组和右美托咪定组(Dex组)。Dex组CPB前15 min开始静脉输注右美托咪定5μg/kg,CPB期间以5μg·kg^-1·h^-1的速率静脉输注。CPB结束后2 h时,取血样行血气分析,计算氧合指数(OI)和呼吸指数(RI)。放血处死大鼠,取肺组织,测定湿/干重(W/D)比值,观察病理学结果并行肺损伤评分;采用ELISA法检测肺组织TNF-α和IL-6含量;采用Western blot法确定p-JAK2/JAK2比值和p-STAT3/STAT3比值。结果与S组比较,其余2组肺损伤评分、W/D比值和RI升高,OI降低,TNF-α和IL-6含量、p-JAK2/JAK2比值和p-STAT3/STAT3比值升高(P<0.05);与CPB组比较,Dex组肺损伤评分、W/D比值和RI降低,OI降低升高,TNF-α和IL-6含量、p-JAK2/JAK2比值和p-STAT3/STAT3比值降低(P<0.05)。结论右美托咪定减轻CPB大鼠肺损伤的机制可能与抑制JAK2/STAT3信号通路,进而减轻肺组织炎症反应有关。
Objective To evaluate the effect of dexmedetomidine on Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway in lung tissues in a rat model of cardiopulmonary bypass(CPB).Methods Twenty-four clean-grade healthy male Sprague-Dawley rats,weighing 320-350 g,aged 12-16 weeks,were randomly divided into sham operation group(group S),CBP group,and dexmedetomidine group(group Dex),with 8 rats in each group.In group Dex,dexmedetomidine was intravenously infused in a dose of 5μg/kg starting from 15 min before CPB followed by infusion of 5μg·kg-1·h-1 during CPB.Blood samples were collected at 2 h after the end of CPB for blood gas analysis,and oxygenation index(OI)and respiratory index(RI)were calculated.Then the rats were sacrificed by bloodletting.The lung tissues were removed for microscopic examination of the pathological changes which were scored and for determination of wet/dry weight ratio(W/D ratio),contents of tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)(by enzyme-linked immunosorbent assay),and expression of JAK2,STAT3,phosphorylated JAK2(p-JAK2)and phosphorylated STAT3(p-STAT3)(by Western blot).The p-JAK2/JAK2 and p-STAT3/STAT3 ratios were calculated.Results Compared with group S,the lung injury score,W/D ratio and RI were significantly increased,OI was decreased,the contents of TNF-αand IL-6,p-JAK2/JAK2 ratio and p-STAT3/STAT3 ratio were increased in the other two groups(P<0.05).Compared with group CPB,the lung injury score,W/D ratio and RI were significantly decreased,OI was increased,the contents of TNF-αand IL-6,p-JAK2/JAK2 ratio and p-STAT3/STAT3 ratio were decreased in group Dex(P<0.05).Conclusion The mechanism by which dexmedetomidine attenuates CPB-induced lung injury may be related to inhibiting JAK2/STAT3 signaling pathway and reducing inflammatory responses in lung tissues of rats.
作者
赵石磊
曹惠鹃
李俞羲
张铁铮
孙莹杰
范红娜
Zhao Shilei;Cao Huijuan;Li Yuxi;Zhang Tiezheng;Sun Yingjie;Fan Hongna(Department of Anesthesiology,Northern Theater General Hospital,Shenyang 110016,China)
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2020年第4期425-428,共4页
Chinese Journal of Anesthesiology
基金
辽宁省自然科学基金(2019-ZD-1017,2020-MS-041)。
