重组旋毛虫蛋白rTsP38对小鼠肠缺血/再灌注肠损伤的保护作用及机制研究  

The protective effects of rTsP38 on intestinal ischemia /reperfusion injury in mice and its underlying mechanisms

作　　者：刘卫锋[1] 温仕宏[1] 李云胜[1] 沈建通[1] 刘克玄[1] 

机构地区：[1]中山大学附属第一医院麻醉科,广州广东510080

出　　处：《中国药理学通报》2014年第9期1235-1241,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81171847;81270456)

摘　　要：目的探讨重组旋毛虫蛋白rTsP38对小鼠肠缺血/再灌注(I/R)损伤的保护效应,并从巨噬细胞角度初步探讨其机制。方法 BALB/c小鼠随机分为假手术组(S组)、肠I/R伤组(I组)、rTsP38免疫组(T组)和佐剂免疫组(A组)。建立I/R模型前6周,分别给予下述试剂,共3次,每次间隔14 d。S组和I组予PBS 0.2 ml,T组予rTsP38 0.2 ml(含25μg与等体积弗氏完全或不完全佐剂乳化混匀的rTsP38),A组予0.1 ml PBS+0.1 ml弗氏完全或不完全佐剂。结果 I组小鼠肠黏膜损伤严重,改良Chiu's评分明显增高,中性粒细胞明显增多,进食量和体重均明显下降,M2型巨噬细胞标志物Arg-1表达下降,M1型巨噬细胞NOS2表达增加。T组小鼠血清IgG1明显升高(P<0.01),改良Chiu's评分明显降低,中性粒细胞明显减少,细胞增殖明显增多,绒毛高度明显增高,进食量和体重均明显增加,Arg-1和NOS2表达均明显增高,且以Arg-1为主。结论 rTsP38促进Th2型免疫反应和M1向M2型巨噬细胞转变,从而减轻小鼠肠I/R所致肠损伤,促进肠黏膜修复和肠功能恢复。Aim To investigate the the protective effects of a novel recombinant Trichinella spiralis 38 ku protein （ rTsP38 ） on intestinal I/R injury and the po-tential mechanisms. Methods Male BALB/c mice were randomly divided into sham group （ group S） , in-jury group （ group I） , rTsP38 vaccinated group （ group T） and adjuvants vaccinated group （ group A ） , and received subcutaneously phosphate buffer solution （PBS）, PBS, rTsP38, or adjuvants, respectively, at 2-week intervals 6 weeks before the surgical proce-dure. Results Intestinal I/R caused severe intestinal injury evidenced by significant increases in modified Chiu ＇s score and neutrophils infiltration, accompanied by decreases in daily food intake and body weight. The mRNA level of arginase-1 （ Arg-1 ） was decreased and the mRNA level of inducible nitric oxide synthase 2 （ NOS2） was increased in group I. RTsP38 significant-ly ameliorated intestinal injury and improved intestinal function following intestinal I/R accompanied by de-crease in neutrophils infiltration and increase in cell proliferation in the intestine, compared to mice without rTsP38 pretreatment. Fold changes of Arg-1 mRNA level were significantly increased in group T. Conclu-sions These findings indicate that rTsP38 exerts pro-tection on intestinal I/R injury in mice via promoting M2 macrophages polarization.

关 键 词：再灌注损伤 巨噬细胞 小肠 炎症 中性粒细胞 旋毛虫 

分 类 号：R-332[医药卫生] R329.24