重组人IL-6对NOD小鼠IDDM发病的影响及机制研究

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目的 探讨重组人白细胞介素 6(rhIL 6)对NOD小鼠自发性和环磷酰胺 (CY)诱发性Ⅰ型糖尿病 (IDDM)的影响及相关机制。方法 通过观察NOD小鼠用药后血糖和尿糖水平、胰腺组织病理学特征 ,及血清抗CD3抗体、LPS诱导的炎症因子IFN γ、TNF α水平的变化 ,以及CY诱导ID DM发生率 ,确定rhIL 6的抗IDDM作用。结果  4wk龄♀NOD小鼠连续注射rhIL 6 1 6wk后 ,胰岛炎即胰腺淋巴细胞、单核细胞浸润明显减少 ,糖尿病的发病率明显降低(33 % )。与空白对照组相比 ,血清中炎症因子IFN γ、TNF α水平也呈显著的下降趋势。 1 2wk龄NOD小鼠连续 8wk应用rhIL 6 ,糖尿病发生率则无明显变化 ,且实验中未观察到rhIL 6对CY诱发IDDM的保护作用。结论 rhIL 6早期预防用药可降低NOD小鼠自发性IDDM的发生 ,该保护作用可能与其降低炎症因子TNF α、IFN γ分泌有关 Objective To investigate the effect of recombinant human interleukin 6 (rhIL 6) on idiopathic and cyclophosphamide (CY) -induced type 1 diabetes mellitus (IDDM) in NOD mice and its related mechanisms. Methods The levels of blood glucose and urine glucose, the histopathological features of pancreas, serum anti-CD3 antibody, the levels of IFNγ and TNFα induced by LPS, and the incidence of IDDM induced by CY were observed to determine the effect of rhIL 6 anti-IDDM effect. Results 4wk ♀NOD mice were injected rhIL 6 1 6wk, pancreatitis and pancreatic lymphocytes, monocytes infiltration significantly reduced, the incidence of diabetes was significantly reduced (33%). Compared with the blank control group, serum inflammatory cytokines IFNγ, TNFα levels also showed a significant downward trend. 1 2-week-old NOD mice were treated with rhIL 6 for 8 weeks. The incidence of diabetes did not change significantly. No protective effect of rhIL 6 on CYP-induced IDDM was observed in the experiment. Conclusion Early prevention of rhIL-6 can reduce spontaneous IDDM in NOD mice, which may be related to the decrease of inflammatory cytokines TNFα and IFNγ
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