γ-氨基丁酸对1型糖尿病小鼠胰岛功能及脾CD4、主要组织相容复合物分子Ⅱ表达影响的研究

Impacts of GABA on islets of pancreas and CD4 and MHC-Ⅱ expression of spleen in T1DM mice

目的探讨T1DM中γ-氨基丁酸(GABA)对胰岛α、β细胞及脾抗原提呈功能的影响。方法腹腔注射STZ,同时通过自由饮水方式摄入GABA建立T1DM的GABA干预小鼠模型,56只小鼠分为正常对照(NC)组(n=8)、T1DM组(n=24)及GABA组(n=24)。检测各组FBG、胰腺Ins、胰升血糖素(Glu)、脾CD4、主要组织相容复合物分子Ⅱ(MHC-Ⅱ)的表达。结果 GABA组FBG在第14天升高,28 d后降低(P<0.01)。与NC组比较,T1DM、GABA组Ins阳性细胞从第14天起平均光密度值升高(P<0.05),从第7天起面数密度值降低(P<0.05或P<0.01)。但从第28天起,GABA组面数密度值较T1DM组升高(P<0.05)。T1DM、GABA组Glu阳性细胞面数密度值较NC组升高(P<0.05)。与NC组比较,TIDM、GABA组CD4表达从第14天起升高(P<0.05或P<0.01)。GABA组CD4表达在第28天低于TIDM组(P<0.05)。与NC组比较,TIDM、GABA组MHC-Ⅱ蛋白表达在第28天升高(P<0.05);GABA处理组MHC-Ⅱ表达在第42天低于TIDM组(P<0.05)。结论 GABA为一种免疫抑制物质,其能抑制T1DM小鼠过强的免疫功能且促进胰岛β细胞数量增加,稳定BG。

Objective To determine the effects of γ-aminobutyric acid(GABA)on islets and antigen presentation function of spleen in T1DM mice.Methods C57/BL6 J mice were injected by STZ to induce T1DM model.56 mice were then divided into GABA intervention group(GABA),T1DM group and normal control group(NC).All these mice were sacrificed for detecting fasting blood glucose(FBG),the mean density of insulin and glucagon of islets,and CD4 and MHC-Ⅱ expression of spleen.Results Firstly,the level of FBG increased but then decreased in the later phase in GABA group(P<0.01).Secondly,compared with NC group,the mean density of insulin of islets in both T1DM and GABA groups increased from day 14 after STZ injection(P<0.05),along with a losing of insulin-positive cells.Compared with T1DM group,the number of insulin-positive cells in GABA group increased from day 28(P<0.05).However,it had no significant impact on glucagon-positive cells.Furthermore,in contrast to T1DM group,lower expression of CD4 at day 28(P<0.05)and lower MCH-Ⅱ expression at day 42(P<0.05)were observed in GABA group.Conclusion GABA may help stabilize blood sugar in T1DM by increasing the number of β cells and delaying the activity of overactive T cells and antigen presentation cells of spleen.