山莨菪碱预处理对大鼠肝缺血再灌注诱发肺损伤的影响
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摘要
目的:探讨山莨菪碱预处理对大鼠肝缺血再灌注诱发肺损伤的影响。方法:48只SD健康雄性大鼠,采用随机数字表法,分为假手术组(S组)、肝缺血再灌注组(IR组)和山莨菪碱预处理组(A组),各16只。S组只做解剖肝门,IR组和A组制备70%大部分肝缺血再灌注损伤模型。A组于阻断肝血流前30 min,静脉注射山莨菪碱2 mg/kg,S组和IR组静脉注射等剂量的0.9%氯化钠溶液。大鼠于再灌注后3 h处死,取肺脏组织,HE染色,光镜下观察病理学结果。计算肺湿/干重(W/D)比值。采用硫代巴比妥酸法测定丙二醛(MDA),黄嘌呤氧化酶法测定超氧化物歧化酶(SOD),氧化氢还原法测定髓过氧化物酶(MPO)的表达;采用免疫组织化学法测定肺组织血红素氧合酶-1(HO-1)和诱导型一氧化氮合酶(iNOS)蛋白的表达。结果:肺组织HE染色病理改变,IR组和A组肺损伤较S组重,A组肺损伤较IR组轻;与S组比较,IR组和A组肺组织W/D比值、MDA含量、MPO活性、HO-1和iNOS蛋白表达均明显增高(P<0.01),SOD活性明显降低(P<0.01);与IR组比较,A组肺组织W/D比值、MDA含量、MPO活性、iNOS蛋白表达均明显降低(P<0.01),肺组织HO-1蛋白表达和SOD活性均明显升高(P<0.01)。结论:山莨菪碱预处理可减轻大鼠肝缺血再灌注诱发的肺损伤。
Objective:To investigate the effects of anisodamine pretreatment on the lung injury induced by hepatic ischemia-reperfusion in rats.Methods:Forty-eight healthy male Sprague-Dawley rats were randomly divided into the sham operation group(group S),hepatic ischemia-reperfusion group(group IR) and anisodamine group(group A) using a random number table(16 rats each group).The hepatic portal in group S was dissected,and the ischemia-reperfusion model of 70% liver in group IR and group A were established.The group A was injected with 2 mg/kg anisodamine before 30 min of blocking liver blood flow and the group S and group IR were injected with the same volume of 0.9% sodium chloride solution.The rats were sacrificed after 3 h of reperfusion,the lung tissue was harvested,stained using HE,and the result of which was observed under light microscope.The ratio of wet to dry(W/D) of lung weight was calculated.The levels of malondialdehyde(MDA),superoxide dismutase(SOD) and myeloperoxidase(MPO) in lung tissue were detected using thiobaituricacid,xanthinoxidase and Hydrogen oxide reduction method,respectively.The expression levels of heme oxygenase-1(HO-1) and inducible nitric oxide synthase(iNOS) in lung tissue were determined by immunohistochemistry.Results:The results of HE staining in lung tissue showed that the lung injury in IR and A groups were more serious than that in group S,and the lung injury in group A was lighter than that in group IR.Compared with the group S,the ratio of W/D,MDA content,MPO activity and HO-1 and iNOS protein expression level significantly increased(P<0.01),and the SOD activity significantly decreased in IR and A groups(P<0.01).Compared with the group IR,the ratio of W/D,MDA content,MPO activity and iNOS protein expression level significantly decreased(P<0.01),and the HO-1 protein level and SOD activity in lung tissue significantly increased in group A(P<0.01).Conclusions:Anisodamine pretreatment can alleviate the lung injury induced by hepatic ischemia-reperfusion in rats.
Objective:To investigate the effects of anisodamine pretreatment on the lung injury induced by hepatic ischemia-reperfusion in rats.Methods:Forty-eight healthy male Sprague-Dawley rats were randomly divided into the sham operation group(group S),hepatic ischemia-reperfusion group(group IR) and anisodamine group(group A) using a random number table(16 rats each group).The hepatic portal in group S was dissected,and the ischemia-reperfusion model of 70% liver in group IR and group A were established.The group A was injected with 2 mg/kg anisodamine before 30 min of blocking liver blood flow and the group S and group IR were injected with the same volume of 0.9% sodium chloride solution.The rats were sacrificed after 3 h of reperfusion,the lung tissue was harvested,stained using HE,and the result of which was observed under light microscope.The ratio of wet to dry(W/D) of lung weight was calculated.The levels of malondialdehyde(MDA),superoxide dismutase(SOD) and myeloperoxidase(MPO) in lung tissue were detected using thiobaituricacid,xanthinoxidase and Hydrogen oxide reduction method,respectively.The expression levels of heme oxygenase-1(HO-1) and inducible nitric oxide synthase(iNOS) in lung tissue were determined by immunohistochemistry.Results:The results of HE staining in lung tissue showed that the lung injury in IR and A groups were more serious than that in group S,and the lung injury in group A was lighter than that in group IR.Compared with the group S,the ratio of W/D,MDA content,MPO activity and HO-1 and iNOS protein expression level significantly increased(P<0.01),and the SOD activity significantly decreased in IR and A groups(P<0.01).Compared with the group IR,the ratio of W/D,MDA content,MPO activity and iNOS protein expression level significantly decreased(P<0.01),and the HO-1 protein level and SOD activity in lung tissue significantly increased in group A(P<0.01).Conclusions:Anisodamine pretreatment can alleviate the lung injury induced by hepatic ischemia-reperfusion in rats.
引文
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[10] 杨定华,张华,黄毓,等.HO-1的表达对肝脏缺血再灌注损伤的保护作用[J].南方医科大学学报,2009,29(11):2329.
[11] MATSUI T,NAGAFUJI T,KUMANISHI T,et al.Role of nitric oxide in pathogenesis underlying ischemic cerebral damage[J].Cellular Molecular Neurob,1999,19(1):177.
[2] NAUTA RJ,TSIMOYIANNIS E,URIBE M,et al.Oxygen-derived free radical in hepatic ischemia and reperfusion injury in the rat[J].Surg Gynecol Obstet,1990,17:120.
[3] 谭敬,周荣胜,刘庆波,等.肝缺血再灌注损伤对大鼠肺组织HO-1和iNOS表达的影响[J].山西医科大学学报,2015,46(9):861.
[4] ZHANG WW,XU ZP,CUI YY,et al.Peripheral cholinoceptor antagonist anisodamine counteracts cholinergic adverse effects and facilitates cognitive amelioration of rivastigmine[J].J Neural Transm,2009,116(12):1643.
[5] 孙凯,杨丽敏.山莨菪碱的药理和临床研究进展[J].世界临床药物,2010,31(3):182.
[6] 尹文,虎晓岷,袁静,等.山莨菪碱对多器官功能障碍综合征保护机制的实验研究[J].中国医师杂志,2004,6(1):8.
[7] 董满库,崔彦,陈昌玮,等.山莨菪碱对大鼠肝脏缺血再灌注损伤保护作用的实验研究[J].中国普外基础与临床杂志,2001,8(5):295.
[8] 董满库,崔彦,周立艳,等.山莨菪碱对肝脏缺血再灌注后氧自由基的影响[J].世界华人消化杂志,2003,11(1):82.
[9] 夏春秋,仲崇俊,张亚年.山莨菪碱对肺缺血(再灌注损伤的保护机制[J].中国微循环,2006,10(3):221.
[10] 杨定华,张华,黄毓,等.HO-1的表达对肝脏缺血再灌注损伤的保护作用[J].南方医科大学学报,2009,29(11):2329.
[11] MATSUI T,NAGAFUJI T,KUMANISHI T,et al.Role of nitric oxide in pathogenesis underlying ischemic cerebral damage[J].Cellular Molecular Neurob,1999,19(1):177.