L-精氨酸通过抑制凋亡途径对脂多糖导致的急性肺损伤的作用(英文)  

Effects of L-arginine on lipopolysaccharides-induced acute lung injury by inhibiting apoptotic pathway

作　　者：李立萍[1] 张建新[1] 李兰芳[1] 

机构地区：[1]河北省医学科学院药物研究所,河北石家庄050021

出　　处：《中国药理学与毒理学杂志》2009年第6期417-422,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：supported by Scientific Research Foundation of the State Human Resource Ministry for Returned Chinese Scholars(9900789);Hebei Province Doctoral Foundation(99547015D)~~

摘　　要：目的探讨一氧化氮供体L-精氨酸(L-Arg)对大鼠不同病程阶段的急性肺损伤(ALI)的影响及机制。方法采用注射内毒素脂多糖(LPS)的方法制备大鼠肺损伤模型。健康雄性SD大鼠,随机分为:①对照组;②LPS组;③L-Arg治疗组。各组按治疗时间又分为给LPS1h后治疗3h(1h+3h)组和给LPS6h后治疗3h(6h+3h)组,并在给予LPS1和6h后再分别ip给予生理盐水(对照组及LPS组)和L-Arg500mg.kg-1(L-Arg治疗组)治疗3h。采用流式细胞术检测肺细胞凋亡率;Western蛋白印迹法检测胱天蛋白酶3(caspase3)蛋白的表达;免疫组化法测定Bcl-2和Bax蛋白的表达;电镜观察肺组织病理变化。结果与对照组比较,LPS1h+3h及LPS6h+3h组细胞凋亡率和caspase3蛋白表达明显升高,Bcl-2蛋白表达下降,Bax表达增加,Bcl-2/Bax比值降低,肺组织出现明显的病理变化。与LPS1h+3h组相比,L-Arg1h+3h组细胞凋亡率〔(23.8±2.8)%vs(15.4±2.3)%〕,caspase3(0.80±0.06vs0.67±0.10)和Bax蛋白表达(0.115±0.012vs0.091±0.014)显著降低,Bcl-2蛋白表达(0.067±0.011vs0.075±0.009)和Bcl-2/Bax比值(0.586±0.114vs0.833±0.142)显著升高;肺组织病理改变明显减轻。L-Arg6h+3h组细胞凋亡率和caspase3蛋白表达低于LPS6h+3h组,肺组织病理改变稍有减轻。结论较早给予L-Arg可减轻ALI,其机制可能与降低caspase3和Bax蛋白表达、增强Bcl-2蛋白表达有关。AIM To investigate the effect and mechanism of L-arginine（L-Arg） on lipopolysaccharides（LPS）-induced acute lung injury（ALI）.METHODSModels of ALI were established by injection（iv） with LPS 5 mg·kg-1 in male SD rats.The rats were randomly divided into 3 groups：① saline group;② LPS group;③ L-Arg group.The rats in each group were further divided into 2 subgroups according to L-Arg-supplemented time：1 h＋3 h group and 6 h＋3 h group.L-Arg 500 mg·kg-1 or saline（saline and LPS groups） was administrated at 1 or 6 h after LPS injection,respectively.The treatment lasted for 3 h,and the rats were sacrificed at 4 or 9 h after LPS injection.Apoptotic rate,caspase 3,and Bcl-2 and Bax were evaluated by flow cytometry,Western blot analysis and immunohistochemistry,respectively;meanwhile,the pathological changes of lung tissue were observed by electron microscope.RESULTS Compared with saline group,apoptosis of pulmonary cells and caspase 3 expression were significantly increased,Bcl-2 was decreased,while Bax was elevated in alveolar and airway epithelial cells in LPS group.Compared with LPS 1 h＋3 h group,L-Arg 1 h＋3 h decreased apoptotic pulmonary cells〔（23.8±2.8）% vs（15.4±2.3）%〕;moreover,expressions of caspase 3（0.80±0.06 vs 0.67±0.10） and Bax（0.115±0.012 vs 0.091±0.014） were significantly decreased,while expression of Bcl-2（0.067±0.011 vs 0.075±0.009） and Bcl-2/Bax ratio（0.586±0.114 vs 0.833±0.142） in alveolar and airway epithelial cells were markedly increased,and lung damage was alleviated.L-Arg 6 h＋3 h also reduced apoptotic pulmonary cells and caspase 3 expression compared with LPS group,but the lung injury relieved slightly.CONCLUSION Relatively early administration of L-Arg can protect lungs from LPS-induced injury through inhibiting cell apoptosis,as well as increasing the expression of anti-apoptotic protein Bcl-2 and decreasing the expression of proapoptotic protein Bax and caspase 3.

关 键 词：精氨酸 细胞凋亡 呼吸障碍 

分 类 号：R96[医药卫生—药理学]