右美托咪啶对肺缺血/再灌注损伤大鼠促炎介质IL-1β、TNF-α水平的影响及其机制
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摘要
目的:评价右美托咪啶对大鼠肺缺血/再灌注损伤时促炎介质肿瘤坏死因子-α(TNF-α)、白介素1β(IL-1β)的影响及机制。方法:雄性健康SPF级SD大鼠50只,体重250~310 g,8~12周龄,采用随机数字表法分为5组(n=10):假手术组(sham组)、缺血/再灌注损伤组(I/R组)、右美托咪啶组(Dex组)、阿替美唑组(Atip组)、右美托咪啶+阿替美唑组(Dex+Atip组)。采用大鼠在体左侧肺门夹闭30 min再灌注2 h制备缺血/再灌注(I/R)模型,Dex组、Atip组、Dex+Atip组分别在肺门阻断前30 min腹腔注射右美托咪啶(20μg/kg)、阿替美唑(250μg/kg)、右美托咪啶(20μg/kg)和阿替美唑(250μg/kg),其余处理同I/R组。实验结束后留取左肺检测肺湿干重比(W/D)和肺水含量(TLW);光、电镜观察肺组织形态结构变化;ELISA检测血浆中IL-1β及TNF-α的水平。结果:与sham组相比,其余各组W/D、TLW、IL-1β和TNF-α的水平明显升高(P<0.05,P<0.01),光、电镜均显示肺组织结构出现明显损伤性变化;与I/R组、Atip组、Dex+Atip组相比,Dex组W/D、TLW、IL-1β及TNF-α的含量下降(P<0.05,P<0.01),光、电镜下肺组织损伤减轻;I/R组、Atip组、Dex+Atip组两两比较,以上各指标均无统计学差异。结论:右美托咪啶通过降低促炎介质IL-1β、TNF-α浓度减轻大鼠肺缺血/再灌注损伤,其机制可能与激动α_2-肾上腺素受体有关。
Objective: To evaluate the effects and mechanism of the Dexmedetomidine on the levels of proinflammatory mediators interleukin 1 beta( IL-1β) and tumor necrosis factor-α( TNF-α) in ischemia/reperfusion( I/R) rats. Methods: Fifty healthy SPF male SD rats,250 ~ 310 g,8 ~ 12 weeks,were randomly divided into five groups( n = 10) : sham operation group( sham group),I/R group,dexmedetomidine group( Dex group),atipamezole group( Atip group),dexmedetomidine plus atipamezole( Dex + Atip group). The I/R model was established by clipping hilus of left lung for 30 min and then reperfusion for 2 h. Dex group,Atip group and Dex + Atip group were performed by intraperitoneal injection dexmedetomidine( 20 μg/kg),atipamezole( 250 μg/kg),Dexmedetomidine( 20 μg/kg) + atipamezole( 250 μg/kg) respectively 30 min in advance before hilus of left lung was clipped,the rest of the process was the same with I/R group. After the experiment the rats were killed and the left lung tissues to determine the lung wet/dry weight( W/D)and total lung water content( TLW); Ultra structure of lung tissues were observed under light microscope and electron microscope; IL-1β and TNF-α levels were determined by using ELISA. Results: Compared with the sham group,the W/D、TLW、IL-1β and TNF-α in other groups were increased significantly( P < 0. 05). The structure damages of lung tissues observed under light microscope and electron microscope in other groups were more serious than that of sham group. Compared with I/R、Atip、Dex + Atip group,the levels of W/D、TLW,IL-1β and TNF-α in Dex group were lower( P < 0. 05),the structure damages of lung tissues observed under light microscopy and electron microscope in Dex group were slighter. There was no significant difference of the above parameters among I/R、Atip、Dex + Atip group. Conclusion: Dexmedetomidine can alleviate ischemia/reperfusion injury in rat lung through lowering the level of proinflammatory mediators IL-1β and TNF-α,the possible mechanism may be through stimulation of α_2 adrenaline receptors.
Objective: To evaluate the effects and mechanism of the Dexmedetomidine on the levels of proinflammatory mediators interleukin 1 beta( IL-1β) and tumor necrosis factor-α( TNF-α) in ischemia/reperfusion( I/R) rats. Methods: Fifty healthy SPF male SD rats,250 ~ 310 g,8 ~ 12 weeks,were randomly divided into five groups( n = 10) : sham operation group( sham group),I/R group,dexmedetomidine group( Dex group),atipamezole group( Atip group),dexmedetomidine plus atipamezole( Dex + Atip group). The I/R model was established by clipping hilus of left lung for 30 min and then reperfusion for 2 h. Dex group,Atip group and Dex + Atip group were performed by intraperitoneal injection dexmedetomidine( 20 μg/kg),atipamezole( 250 μg/kg),Dexmedetomidine( 20 μg/kg) + atipamezole( 250 μg/kg) respectively 30 min in advance before hilus of left lung was clipped,the rest of the process was the same with I/R group. After the experiment the rats were killed and the left lung tissues to determine the lung wet/dry weight( W/D)and total lung water content( TLW); Ultra structure of lung tissues were observed under light microscope and electron microscope; IL-1β and TNF-α levels were determined by using ELISA. Results: Compared with the sham group,the W/D、TLW、IL-1β and TNF-α in other groups were increased significantly( P < 0. 05). The structure damages of lung tissues observed under light microscope and electron microscope in other groups were more serious than that of sham group. Compared with I/R、Atip、Dex + Atip group,the levels of W/D、TLW,IL-1β and TNF-α in Dex group were lower( P < 0. 05),the structure damages of lung tissues observed under light microscopy and electron microscope in Dex group were slighter. There was no significant difference of the above parameters among I/R、Atip、Dex + Atip group. Conclusion: Dexmedetomidine can alleviate ischemia/reperfusion injury in rat lung through lowering the level of proinflammatory mediators IL-1β and TNF-α,the possible mechanism may be through stimulation of α_2 adrenaline receptors.
引文
[1]刘备,唐冬梅,杜宁,等.七氟烷预处理联合后处理对肺缺血再灌注损伤大鼠的保护作用及机制[J].山东医药,2015,55(17):17-19.
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[10]何金波,宋冬,罗梓垠,等.右美托咪定对大鼠I/R损伤肺组织TLR4表达及保护作用的影响[J].中国应用生理学杂志,2016,32(4):356-360.
[11]常春荣,韩东,孙尚敏,等.牙周基础治疗对慢性牙周炎患者龈沟液白细胞介素6、肿瘤坏死因子α及血清高敏C反应蛋白的影响[J].中国医科大学学报,2013,42(2):135-137.
[12]付锐,项和平,杨硎琦,等.降钙素原、C反应蛋白、肿瘤坏死因子、游离DNA对多发伤患者发生多器官功能障碍综合征的预测价值[J].中华急诊医学杂志,2013,22(8):850-854.
[13]袁艳平,李长贵.痛风性关节炎患者血清白细胞介素-1β、肿瘤坏死因子-α环氧化酶-2水平的动态变化研究[J].中华风湿病学杂志,2013,17(12):818-822.
[14]Man9ek-Keber M,Jerala R.Postulates for validating TLR4 agonists[J].Eur J Immunol,2015,45(2):356-370.
[15]黄翠源,潘灵辉,林飞,等.肺泡巨噬细胞TLR4/My D88信号通路参与并介导了机械通气所致的肺损伤[J].细胞与分子免疫学杂志,2015,31(2):182-185.
[16]刘亚坤,何金波,陈海娥,等.血必净注射液对缺氧/复氧大鼠心肌TLR4—NF-κB—TNF-α通路的影响[J].中国中西医结合杂志,2014,34(12):1463-1468.
[17]Xing B,Chen H,Wang L,et al.Ozone oxidative preconditioning protects the rat kidney from reperfusion injury via modulation of the TLR4-NF-κB pathway[J].Acta Cir Bras,2015,30(1):60-66.
[18]何金波,包财盈,叶玉柱,等.缺氧-复氧大鼠心肌中IL-1β浓度的动态变化及意义[J].中国应用生理学杂志,2015,31(1):27-30.
[19]Hua F,Tang H,Wang J,et al.TAK-242,an antagonist for Toll-like receptor 4,protects against acute cerebral ischemia/reperfusion injury in mice[J].J Cereb Blood Flow Metab,2015,35(4):536-42.
[20]尹红,吴健,陈卫民.小剂量右美托咪定持续输注对全麻高血压患者血流动力学的影响[J].临床麻醉学杂志,2013,29(12):1181-1183.
[2]倪程耀,陈新,吴胜军.免疫因素在大鼠肺缺血再灌注损伤中的作用[J].中国老年学杂志,2014,34(18):5192-5193.
[3]王赫,李晓倩,马虹,等.鞘内注射右美托咪啶预处理在兔脊髓缺血再灌注损伤的保护作用[J].中国医师杂志,2013,15(8):1032-1036.
[4]Bagcik E,Ozkardesler S,Boztas N,et al.Effects of dexmedetomidine in conjunction with remote ischemic preconditioning on renal ischemia-reperfusion injury in rats[J].Rev Bras Anestesiol,2014,64(6):382-390.
[5]Sahin T,Begec Z,Toprak HI,et al.The effects of dexmedetomidine on liver ischemia-reperfusion injury in rats[J].J Surg Res,2013,183(1):385-390.
[6]罗梓垠,郭长满,项冰倩,等.右美托咪定对肺缺血/再灌注损伤小鼠内质网应激相关分子Caspase-12表达的影响[J].中国应用生理学杂志,2016,32(2):164-168.
[7]Mantz J,Josserand J,Hamada S.Dexmedetomidine:new insights[J].Eur J Anaesthesiol,2011,28(1):3-6.
[8]崔云凤,宋智敏,周姝,等.右美托咪定辅舒芬太尼用于全麻病人的术后镇痛[J].中国实验诊断学,2013,17(2):321-323.
[9]Luan HF,Zhao ZB,Feng JY,et al.Prevention of etomidate-induced myoclonus during anesthetic induction by pretreatment with dexmedetomidine[J].Braz J Med Biol Res,2015,48(2):186-190.
[10]何金波,宋冬,罗梓垠,等.右美托咪定对大鼠I/R损伤肺组织TLR4表达及保护作用的影响[J].中国应用生理学杂志,2016,32(4):356-360.
[11]常春荣,韩东,孙尚敏,等.牙周基础治疗对慢性牙周炎患者龈沟液白细胞介素6、肿瘤坏死因子α及血清高敏C反应蛋白的影响[J].中国医科大学学报,2013,42(2):135-137.
[12]付锐,项和平,杨硎琦,等.降钙素原、C反应蛋白、肿瘤坏死因子、游离DNA对多发伤患者发生多器官功能障碍综合征的预测价值[J].中华急诊医学杂志,2013,22(8):850-854.
[13]袁艳平,李长贵.痛风性关节炎患者血清白细胞介素-1β、肿瘤坏死因子-α环氧化酶-2水平的动态变化研究[J].中华风湿病学杂志,2013,17(12):818-822.
[14]Man9ek-Keber M,Jerala R.Postulates for validating TLR4 agonists[J].Eur J Immunol,2015,45(2):356-370.
[15]黄翠源,潘灵辉,林飞,等.肺泡巨噬细胞TLR4/My D88信号通路参与并介导了机械通气所致的肺损伤[J].细胞与分子免疫学杂志,2015,31(2):182-185.
[16]刘亚坤,何金波,陈海娥,等.血必净注射液对缺氧/复氧大鼠心肌TLR4—NF-κB—TNF-α通路的影响[J].中国中西医结合杂志,2014,34(12):1463-1468.
[17]Xing B,Chen H,Wang L,et al.Ozone oxidative preconditioning protects the rat kidney from reperfusion injury via modulation of the TLR4-NF-κB pathway[J].Acta Cir Bras,2015,30(1):60-66.
[18]何金波,包财盈,叶玉柱,等.缺氧-复氧大鼠心肌中IL-1β浓度的动态变化及意义[J].中国应用生理学杂志,2015,31(1):27-30.
[19]Hua F,Tang H,Wang J,et al.TAK-242,an antagonist for Toll-like receptor 4,protects against acute cerebral ischemia/reperfusion injury in mice[J].J Cereb Blood Flow Metab,2015,35(4):536-42.
[20]尹红,吴健,陈卫民.小剂量右美托咪定持续输注对全麻高血压患者血流动力学的影响[J].临床麻醉学杂志,2013,29(12):1181-1183.