摘要
目的 探讨1, 25 (OH)2D3 阻断NOD/Lt小鼠发生1型糖尿病的免疫机制。方法 60只4周龄NOD/Lt小鼠(25g)分为2组,组1隔天腹腔注射1, 25 (OH)2D3 (5μg/kg),组2腹腔注射花生油作为对照。所有小鼠在第1天和第15天腹腔注射环磷酰胺以加速糖尿病的发生,第30天处死并观察。免疫组化检测Bcl 2,Bax在胰岛和T淋巴细胞的表达;流式细胞仪检测T淋巴细胞亚群分布及凋亡率;RT PCR检测Th1 /Th2 亚群的漂移。结果 1, 25 (OH)2D3 处理组糖尿病发病率下降,脾T淋巴细胞凋亡率增加〔(55. 8±5. 4)% vs(28. 9±3. 6)%,P<0. 05〕;CD4+Th2 亚群增加(IL 4和IL 10mRNA显著增加, P<0. 01)。结论 1, 25 (OH)2D3 通过加速T淋巴细胞的凋亡以减轻细胞免疫反应并最终延缓胰岛β细胞的凋亡,并使CD4+Th1 亚群向CD4+Th2 亚群漂移,导致NOL/Lt小鼠1型糖尿病发病率下降。
Objective To study the mechanism of 1,25-(OH)_2D_3-blocking the onset of type 1 diabetes in NOD/Lt mice. Methods Sixty of 4-week-old female NOD/Lt mice (25 g) were evenly divided into two groups. Mice in group 1 received intraperitoneal injection of 1,25-(OH)_2D_3 (5 μg/kg) every other day. Mice in group 2 received intraperitoneal injection of peanut oil as controls. All experimental mice were administered intraperitoneal injection of cyclophosphamide (180 mg/kg) on the first day and the 15th day of experiments to accelerate the process of diabetes. All mice were killed on the 30th day of experiment to observe the incidence of diabetes, the degree of insulitis; the expressions of Bcl-2 and Bax were detected with immunohistochemical technique. The distributions of T lymphocyte subpopulations in thymus and spleen and the apoptosis rate of T lymphocytes in spleen were observed by flowcytometry.ThesubpopulationshiftofTh_1/Th_2 was determined by RT-PCR. Results Intraperitoneal injection of 1,25-(OH)_2D_3 to NOD/Lt mice reduced the incidence of diabetes. The insulitis score was lower and the severity of insulitis attenuated in 1,25-(OH)_2D_3 group as compared with those in peanut oil group. However, the apoptosis rate of T lymphocyte in spleen was higher in 1,25-(OH)_2D_3 group than that in peanut oil group 〔(55.8±5.4)% vs (28.9±3.3)%, P<0.05〕. There was a shift from CD4+Th_1 to CD4+Th_2 cells in spleens in 1,25-(OH)_2D_3 group (significantly increased IL-4 and IL-10 mRNA). Conclusion 1,25-(OH)_2D_3 may protect NOD/Lt mice from developing into type 1 diabetes via increasing apoptosis of T lymphocyte which attenuates cytoimmune reaction and delays the apoptosis of islet β cells via shifting of CD4+Th_1 to CD4+Th_2 cells.
出处
《中华内分泌代谢杂志》
CAS
CSCD
北大核心
2005年第2期163-166,共4页
Chinese Journal of Endocrinology and Metabolism
基金
山西省自然科学基金(200219)
山西省归国留学人员科研基金(9913)