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目的观察SHP-2D61G/+酪氨酸磷酸酶激活突变对组织白细胞浸润、细胞因子分泌及多器官损伤的影响。方法分别以SHP-2D61G/+激活突变敲入的模型小鼠和野生型C57BL/6小鼠为研究对象,ELISA法检测小鼠血清和白细胞培养上清液中IL-2及TNF-α浓度;采用常规组织切片和HE染色观察心、肺、脾等组织病理学改变;放射免疫法检测血清中丙氨酸转氨酶和心肌肌钙蛋白I的水平。结果 SHP-2D61G/+激活突变小鼠脾、肺组织中白细胞浸润较野生型对照小鼠明显增加,心肌肥大,出现明显炎症损伤型组织学变化;与野生型对照相比,突变小鼠血清及白细胞培养上清液中IL-2和TNF-α浓度均显著增加(P<0.01),血清丙氨酸转氨酶及心肌肌钙蛋白I水平亦显著增高(P<0.01)。结论 SHP-2D61G/+激活突变增强白细胞分泌炎症因子的能力,促进组织白细胞严重浸润和脾、肺、心等多器官损伤,进而导致多器官功能障碍。
Objective To investigate the effects of SHP-2D61G / + tyrosine phosphatase activating mutation on leukocyte infiltration, cytokine secretion and multiple organ damage. Methods SHP-2D61G / + activation mutant knockout mice and wild type C57BL / 6 mice were used as the research objects. The concentrations of IL-2 and TNF-α in the serum and leukocyte culture supernatants were determined by ELISA. Pathological changes of heart, lung and spleen were observed by routine histological sections and HE staining. Serum levels of alanine aminotransferase and cardiac troponin I were measured by radioimmunoassay. Results The leukocyte infiltration in SHP-2D61G / + -activated mutant mice was significantly higher than that in wild-type control mice and myocardial hypertrophy with obvious histological changes of inflammatory injury. Compared with the wild-type control, the serum and The concentration of IL-2 and TNF-α in leukocyte culture supernatants were significantly increased (P <0.01), serum alanine aminotransferase and cardiac troponin I levels were also significantly increased (P <0.01). Conclusion The SHP-2D61G / + activation mutation enhances the ability of leukocytes to secrete inflammatory factors, and promotes the severe infiltration of tissues and splenic, lung, and heart organ damage, leading to multiple organ dysfunction.