L-瓜氨酸对大鼠胃缺血再灌注损伤的保护作用  

The protective effect of L-citrulline against ischemia/reperfusion-induced gastric mucosal lesions in rats

作　　者：缑灵山[1] 尹翠[1] 田霞[1] 孙凌燕[1] 印晓星[1] 刘毅[1] 

机构地区：[1]徐州医学院药学院,江苏徐州221002

出　　处：《解放军医学杂志》2011年第2期167-169,共3页Medical Journal of Chinese People's Liberation Army

基　　金：江苏省自然科学基金(BK2009253);徐州医学院研究生创新基金(XYCX200913)

摘　　要：目的研究L-瓜氨酸(L-Cit)对胃缺血再灌注损伤(GI/R)的保护作用及其机制。方法雄性SD大鼠50只,随机分为7组,即假手术组,GI/R组,L-Cit高(900mg/kg)、中(600mg/kg)、低(300mg/kg)剂量组,L-Cit(900mg/kg)+L-硝基精氨酸甲酯(L-NAME)组,氨基胍组,每组6～8只。后6组大鼠建立GI/R模型。药物均用生理盐水稀释,L-Cit于缺血前1h灌胃给药,L-NAME(10mg/kg)和氨基胍(100mg/kg)于缺血前30min皮下注射给药。实验结束后取胃计数胃黏膜损伤指数,观察胃黏膜细胞形态学变化,测定胃黏膜组织中一氧化氮(NO)、丙二醛(MDA)含量及超氧化物歧化酶(SOD)、髓过氧化物氧化酶(MPO)、总一氧化氮合酶(TNOS)、诱导型NOS(iNOS)和结构型NOS(cNOS)活性并进行组间比较。结果 L-Cit对缺血再灌注诱发的大鼠胃黏膜损伤具有抑制作用,低、中、高剂量组的损伤抑制率分别为57.4%7、6.0%9、3.9%,且可维持胃黏膜缺血及再灌注期SOD活力,降低TNOSi、NOS、MPO活性,上调cNOS活性,减少MDA含量,减轻缺血再灌注后胃黏膜病理损伤。结论 L-瓜氨酸对缺血再灌注引起的胃黏膜损伤具有保护作用,其作用机制可能与调节NOS活性、抑制淋巴细胞浸润、清除和抑制胃缺血再灌注时氧自由基产生有关。Objective To study the protective effect and underlying mechanisms of L-citrulline against gastric mucosal lesions induced by ischemia/reperfusion（I/R） in rats.Methods Fifty SD rats were randomly divided into 7 groups（n=6-8）.Under anesthesia,the celiac artery was clamped for 30 minutes,and then the circulation was recovered by removal of the clamp.The total area of erosions and the content of nitrite/nitrate（NO） and malondialdehyde（MDA） in the gastric mucosa were examined 60 minutes after the reperfusion.Moreover,the enzymatic activities of superoxide dismutase（SOD）,total NO synthase（NOS）,constitutive NOS（cNOS）,inducible NOS（iNOS） and myeloperoxidase（MPO） were determined.Histological analysis of the lesions was also carried out.Results Following I/R,hemorrhagic lesions were generated in the mucosa.Prior administration of L-citrulline（300,600,900 mg/kg） before ischemia significantly ameliorated the gastric damage induced by I/R in a dose-dependent manner.The index of lymphocyte infiltration,NO content and lipid peroxidation were reduced significantly（P〈0.05）.In addition,the increase of activities of total NOS and iNOS,and the decrease of cNOS activity in the gastric mucosa were also significantly attenuated by L-citrulline.Conclusion L-citrulline has a protective effect against I/R-induced gastric mucosal lesions in rats at least partly by inhibiting oxidative stress and reducing lymphocyte infiltration into the mucosa via regulating the production of NO.

关 键 词：瓜氨酸 胃黏膜 再灌注损伤 一氧化氮合酶 

分 类 号：R573.13[医药卫生—消化系统]