霉酚酸酯对非肥胖性糖尿病小鼠胰岛炎和胰岛β细胞凋亡的保护作用

The protective effect of mycophenolate mofetil (MMF) on insulitis and pancreatic β-cell apoptosis in NOD mice

目的:探讨霉酚酸酯(mycophenolate mofetil,MMF)对非肥胖性糖尿病小鼠(non-obese diabetic mice,NOD)胰岛炎和胰岛β细胞凋亡的保护作用。方法:8周龄NOD雌性小鼠22只分为两组,每组11只,干预组给予霉酚酸酯30mg/kg灌胃,对照组给予等量的生理盐水。两组小鼠饲养期间定期监测其血糖水平。30天实验结束时,每组取5只小鼠处死,行HE染色观察胰岛炎程度,TUNEL法检测胰岛β细胞凋亡率。余下小鼠观察到发生糖尿病或20周处死。结果:干预前两组小鼠血糖均在正常水平。干预期间和干预期满后,MMF干预组小鼠血糖与生理盐水对照组之间无差异(P>0.05);MMF组胰岛炎严重程度及胰岛β细胞凋亡率较生理盐水对照组明显减轻(P<0.01)。结论:MMF可以在早期抑制NOD小鼠的胰岛炎和胰岛β细胞凋亡,从而减轻胰腺损伤。如果在糖尿病发病前给予MMF可能延缓或防止糖尿病的发生。

Objective：To investigate the protective effect of mycophenolate mofetil（MMF） on insulitis and pancreatic β-cell apoptosis in NOD mice. Methods：Twenty-two female NOD mice of eight-week age were randomly divided into the following two groups：the control group and the MMF-treated group. MMF（30 mg/kg） was administered daily by intragastric intubations throughout the experimental period（30 days） and the control group received an equivalent amount of 0.9% NaCl intragastrically. Before and during all experi-ments, blood glucose of all mice were assessed. Following treatment, five mice of each group were anaesthetized and then were killed to remove pancreas immediately. The rest mice were sacrificed when they got diabetes or twenty-week age. The degree of insulitis and the morphological changes of pancreatic β-cells apoptosis were determined by light microscope and TUNEL assay. Results：The con centration of blood glucose in MMF-treated group were as same as those in the control group before and during the experimeni （P 〉 0.05）. The insulitis scores and severity of insulitis and the percentage of β-cell apoptosis in the MMF-treated mice were significantly lower than those of the control group （P 〈 0.01 ）. Conclusion：MMF treatment could ameliorate early pancreatic injury via the inhibi- tion of insulitis and β-cell apoptosis in NOD mice. It suggests that MMF could be effective in delaying and preventing diabetes especially if treatment is started before the onset of diabetes.