周正宇 吴淑燕 李新寅 薛智谋 童建

　　基金项目:苏州市应用基础研究计划资助项目(SYS201011)

　　作者单位：215006苏州大学实验动物中心(周正宇、李新寅、薛智谋)，放射医学与公共卫生学院(童建)

　　通讯作者:童建,E-mail:tongjian@suda.edu.cn

　　【摘要】目的研究雷帕霉素对1型糖尿病(T1DM)小鼠的影响及其分子机制。方法40 mg/kg的STZ腹腔注射C57BL/6小鼠连续5 d建立T1DM模型，正常和T1DM小鼠按2 mg/kg 腹腔注射RAPA连续两周。监测血糖、体重、进食量和饮水量;观测胰岛炎、主要脏器的超微结构和凋亡和自噬的发生;检测脾脏Th1/Th2分群和调节性T细胞。结果RAPA对正常小鼠一般特性及主要脏器的超微结构无明显影响。但可使T1DM小鼠血糖升高、体重下降、采食和饮水量增加(P<0.05)，并加重其胰岛炎程度;诱导其胰腺、肾脏、脾脏和胸腺细胞自噬或凋亡，并使LC3、Beclin1、Caspase-3的表达增加;减少正常和T1DM小鼠的Th1细胞，增加Th2细胞，并上调CD4+CD25+T细胞的数量。结论RAPA既可诱导免疫耐受，发挥免疫抑制作用，又可通过自噬直接破坏胰岛从而加重T1DM代谢紊乱和并发症。

　　【关键词】糖尿病,1型;雷帕霉素;自噬

　　doi:12.3969/j.issn.1006-6187.2011.02.015

　　Effects of rapamycin on immune function of T1DM mouse and the related molecular mechanism

　　ZHOU Zheng-yu, WU Shu-yan, LI Xin-yin, et al. Medical College of Soochow University, Suzhou, 215006, China

　　Corresponding author: TONG Jian, E-mail:tongjian@suda.edu.cn

　　【Abstract】Objective　　To study the effect of rapamycin on immune function of T1DM mouse and its molecular mechanism.MethodsT1DM model of mice was estabolished by multiple low dose of streptozotocin peritoneal injections. Blood glucose, body weight, food intake and water drinking were observed. And islet pathology, ultrastructure, apoptosis and autophagy of kidney, spleen, thymus and pancreas as well as the swarming of spleen T cells were examined.ResultsPapamycin-treated T1DM mice showed that: (1) blood glucose, food intake and amount of water drinking were increased, and BW decreased; (2) Insulitis worsened and expressions of LC3, beclin-l and caspase-3 were increased; (3) Autophagy and apoptosis of the four organs occurred; (4) Numbers of Th2 cells and CD4+CD25+ T cell were increased and Th1 cells decreased.ConclusionsRapamycin can induce an immune tolerance with immune suppresive effects, but can induce autophagy of islet cells with abnormal metabolism and worsened complications.

　　【Key words】Diabetes mellitus, type 1; Rapamycin; Autophagy