硫化氢减弱脂多糖诱导的大鼠急性肺损伤并抑制磷酸化p38 MAPK蛋白表达  

Hydrogen sulfide reduces lipopolysaccharide-induced acute lung injury and inhibits expression of phosphorylated p38 MAPK in rats

作　　者：范亚敏[1] 黄新莉[2] 董泽飞[3] 凌亦凌[2] 

机构地区：[1]邢台医学高等专科学校眼科教研室,邢台054000 [2]河北医科大学病理生理教研室,石家庄050017 [3]邢台医学高等专科学校生理教研室,邢台054000

出　　处：《生理学报》2012年第6期666-672,共7页Acta Physiologica Sinica

基　　金：supported by the National Natural Science Foundation of China (No.30800440);the Natural Science Foundation of Hebei Province of China (No.C2007000830;C2008001040)

摘　　要：本文旨在研究硫化氢(hydrogen sulfide,H2S)抗脂多糖(lipopolysaccharide,LPS)致肺损伤(acute lung injury,ALI)时p38 MAPK信号通路的变化。将大鼠随机分为6组:对照组、LPS组、LPS+NaHS组、LPS+PPG(胱硫醚-γ-裂解酶抑制剂)组、NaHS组和PPG组。各组大鼠均于注射后6h处死并留取肺组织。光镜下观察肺组织形态学变化并计数肺泡间隔中多形核白细胞(polymorphonuclear leucocyte,PMN)数目;检测肺组织髓过氧化物酶(myeloperoxidase,MPO)活性、超氧化物歧化酶(superoxid dismutase,SOD)活性和丙二醛(malondialdehyde,MDA)含量;免疫组织化学染色观察细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)蛋白表达变化;Western blot方法检测肺组织中磷酸化p38 MAPK(p-p38 MAPK)蛋白表达的变化。结果显示,LPS组肺组织出现损伤性变化,同时肺组织中MPO活性、MDA含量、ICAM-1及p-p38 MAPK蛋白表达、肺泡间隔中PMN数目均高于相应对照组,而肺组织中SOD活性较对照组明显降低(均P<0.05),预先腹腔注射NaHS可明显减轻上述变化,预先注入PPG则加剧以上变化(均P<0.05)。肺组织中p-p38 MAPK与ICAM-1表达呈正相关(r=0.923,P<0.01)。结果提示,H2S改善LPS诱导的ALI与抑制p38 MAPK通路、减少ICAM-1的蛋白表达有关。To investigate the influence of hydrogen sulfide （H2S） on p38 MAPK signaling pathway during acute lung injury （ALI） caused by lipopolysaccharide （LPS）, the rats were randomly divided into six groups： control group, LPS group, LPS ＋ NaHS group, LPS ＋ PPG （cystathionine-γ-lyase inhibitor） group, NaHS group and PPG group. The rats were sacrificed 6 h after injection and lung tissues were obtained. The structure of lung tissues and the number of polymorphonuclear leucocyte （PMN） was observed under optical microscope; the lung myeloperoxidase （MPO） activity, superoxide dismutase （SOD） activity and malondialdehyde （MDA） content were tested; intercellular adhesion molecule-1 （ICAM-1） protein expression changes were detected by immunohistochemical staining; phosphorylated p38 MAPK （p-p38 MAPK） protein expression was detected by Western blotting. The results showed that the lung injury in LPS group was observed, at the same time the MPO activity, the content of MDA, ICAM-1 and p-p38 MAPK protein expressions, the number of PMN were all higher than those in control group （all P 0.05）. Pre-injection of NaHS alleviated the changes induced by LPS, while pre-injection of PPG aggravated those alterations （all P 0.05）. ICAM-1 and p-p38 MAPK protein expressionsin lung tissue were positively correlated （r = 0.923, P 0.01）. The results suggest that H2S may reduce LPS-induced ALI through inhibiting the conjugation of p38 MAPK and reducing the expression of ICAM-1.

关 键 词：硫化氢 急性肺损伤 细胞间黏附分子-1 P38 MAPK 

分 类 号：R363[医药卫生—病理学]