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目的探讨链脲佐菌素(STZ)诱导的糖尿病大鼠脾脏免疫损伤及吡格列酮的干预作用。方法 48只8周龄健康雄性SD大鼠,随机分为糖尿病吡格列酮干预组(Pio组)、糖尿病甘精胰岛素干预组(INS组)、单纯糖尿病组(DM组)、正常对照组(CON组)。采用尾静脉注射STZ(45 mg/kg)方法建立糖尿病模型后,Pio组给予吡格列酮[20 mg/(k·d)]灌胃和生理盐水(0.1 ml/d)皮下注射,INS组给予甘精胰岛素[4 U/(kg·d)]皮下注射和生理盐水(2 ml/d)灌胃,DM组和CON组大鼠给予生理盐水(0.1 ml/d)皮下注射和生理盐水(2 ml/d)灌胃。各组大鼠同步饲养,自由进食和饮水。于造模成功后第16周末,处死大鼠并留取大鼠脾脏,分别进行测量重量,通过免疫组化的方法观察CD4~+、CD8~+细胞变化,通过免疫荧光及Masson染色方法观察脾脏免疫球蛋白和胶原纤维含量的变化。结果与CON组比较,DM组大鼠脾脏重量降低,脾脏CD4~+T细胞和CD8~+T细胞增加,而CD4~+/CD8~+T细胞比值降低,免疫荧光IOD值和胶原纤维量均增加(均P<0.05);而Pio组大鼠脾脏重量高于DM组,脾脏CD8~+T细胞低于DM组,CD4~+/CD8~+T细胞比值高于DM组,免疫荧光IOD值低于DM组,胶原纤维量低于DM组(均P<0.05);与INS组比较,Pio组大鼠脾脏免疫荧光IOD值低于INS组(P<0.01),脾脏重量高于INS组(P<0.05)。结论糖尿病大鼠脾脏出现T细胞亚群数目、比例的异常,免疫球蛋白的沉积和纤维化,脾脏萎缩,脾脏受到免疫损伤。吡格列酮可以一定程度上防止脾脏的上述改变,保护脾脏。
Objective To investigate the immunological injury induced by streptozotocin (STZ) in spleen of diabetic rats and the effect of pioglitazone on it. Methods Forty 8-week-old healthy male Sprague-Dawley rats were randomly divided into two groups: the diabetic Pioglitazone intervention group (Pio group), the diabetic insulin glargine intervention group (INS group), the simple diabetic group (DM group), the normal control group . After the diabetic model was established by injecting STZ (45 mg / kg) via the tail vein, Pioglitazone [20 mg / (kd)] was given intragastrically and saline (0.1 ml / d) Rats in DM group and CON group were injected subcutaneously with normal saline (0.1 ml / d) and normal saline (2 ml / d) by intragastric administration of insulin (4 U / kg / d) d) Gavage. Rats in each group were fed at the same time, fed freely and drinking water. At the end of the 16th week after the model was established, the rats were sacrificed and the spleens of the rats were taken for measurement of weight. The changes of CD4 ~ + and CD8 ~ + cells were observed by immunohistochemistry. The spleen was observed by immunofluorescence and Masson staining Changes in immunoglobulin and collagen fiber content. Results Compared with the CON group, the spleen weight, CD4 ~ + T cells and CD8 ~ + T cells in the DM group increased and the ratio of CD4 ~ + / CD8 ~ + T cells decreased (P <0.05). The spleen weight in Pio group was higher than that in DM group. The spleen CD8 ~ + T cells in DM group were lower than DM group. The ratio of CD4 ~ + / CD8 ~ + T cells in DM group was higher than that in DM group Compared with INS group, the IOD of immunofluorescence in Pio group was lower than that in INS group (P <0.01), and the weight of spleen was higher than that in INS group (P <0.05) P <0.05). Conclusion The number of T lymphocyte subsets, the abnormality of proportion, the deposition and fibrosis of immunoglobulin, the atrophy of the spleen and the immune injury of the spleen in the spleen of diabetic rats. Pioglitazone can prevent the above changes of spleen to a certain extent, protect the spleen.