Gab2在SHP-2激活突变导致的小鼠肥大细胞异常增殖活化及其导致器官损伤中的作用  

Gab2 in Relation to Abnormal Proliferation and Activation in Mice Mast Cell and Organ Impairment Induced by Activating Mutant SHP-2 Tyrosine Phosphatase

作　　者：陈吉[1] 陈卓[1] 汪心怡[1] 郑红[1] 瞿成奎[1,2] 汪思应[1] 

机构地区：[1]安徽医科大学基础医学院,合肥230032 [2]CaseWesternReserveUniversity,Cleveland,USA,44106

出　　处：《实验动物与比较医学》2013年第5期329-333,共5页Laboratory Animal and Comparative Medicine

基　　金：国家自然科学基金（编号：30873046,30973424,81272258）;教育部博士点基金（编号：200803660005）;安徽省出国留学回国人员科技项目（编号：2009-2011）

摘　　要：目的 观察接头蛋白Gab2对激活突变SHP-2导致的肥大细胞异常增殖活化是否具有调控作用,对激活突变SHP-2小鼠器官损伤有无影响.方法 用Gab2-/-、SHP-2D61G/＋小鼠杂交建立四种基因型（SHP-2＋/＋、Gab2-/-、SHP-2D61G/＋、SHP-2D61G/＋/Gab2-/-）小鼠为研究对象;取小鼠骨髓细胞用IL-3诱导建立肥大细胞,用MTS法检测不同基因型小鼠肥大细胞对细胞因子刺激增殖反应性;用ELISA法检测小鼠血清及肥大细胞分泌炎症因子水平,放射免疫法检测小鼠血清中丙氨酸转氨酶（ALT）和心肌肌钙蛋白I（cTnI）的水平;用病理组织学技术检测小鼠组织白细胞浸润及器官损伤情况.结果 Gab2缺失后,SHP-2激活突变导致的小鼠肥大细胞异常增殖及活化现象明显改善,对细胞因子增殖反应性下降,相应细胞因子分泌减少,心脏及肝脏组织损伤减轻.结论 Gab2缺失降低了SHP-2激活突变导致的小鼠肥大细胞异常增殖活化和心脏及肝脏组织损伤.Objective To investigate the roles of adaptor protein Gab2 in mast cell abnormal proliferation,activation,and organ damage in SHP-2D61G/＋ mutant mice.Method Four kinds of mouse model genotyped as SHP-2＋/＋,Gab2-/-,SHP-2D61G/＋,and SHP-2D61G/＋/Gab2-/-were generated from crossbreeding of Gab2-/-and SHP-2D61G/＋ mouse.Mouse mast cell was generated from bone marrow cell induced by IL-3,and the proliferation of different genotype mast cells stimulated with cytokine was analyzed by MTS assay;Inflammatory cytokines levels in mouse serum and mast cell secretion were measured by ELISA,and alanine aminotransferase （ALT） and cardiac troponin I （cTnI） levels in serum was determined by radioimmunoassay; leukocyte infiltration in mouse tissues and organ impairment were detected with histopathologic detection.Results The results showed that Gab2 knockout reduced the mice mast cell abnormal proliferation and activation induced by SHP-2D61G/＋ mutation,decreased cytokines secretion accordingly of SHP-2D61G/＋ mice,as well as reduced heart and liver impairment.Conclusion Gab2 knockout weakens the mice mast cell abnormal proliferation and activation induced by SHP-2D61G/＋ mutation,and mitigates the heart and liver damage.

关 键 词：SHP-2 Gab2 肥大细胞异常增殖及活化 器官损伤 

分 类 号：R-332[医药卫生]