CAJ | 학술논문

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,又可通过白噬直接破坏胰岛从而加重T1DM代谢紊乱和并发症.
목적 연구뢰파매소대1형당뇨병(T1DM)소서적영향급기분자궤제.방법 40 mg/kg적STZ복강주사C57BL/6소서련속5 d건립T1DM모형,정상화T1DM소서안2 mg/kg복강주사RAPA련속량주.감측혈당、체중、진식량화음수량;관측이도염、주요장기적초미결구화조망화자서적발생;검측비장Th1/Th2분군화조절성T세포.결과 RAPA대정상소서일반특성급주요장기적초미결구무명현영향.단가사T1DM소서혈당승고、체중하강、채식화음수량증가(P<0.05),병가중기이도염정도;유도기이선、신장、비장화흉선세포자서혹조망,병사LC3、Beclin1、Caspase-3적표체증가;감소정상화T1DM소서적Th1세포,증가Th2세포,병상조CD4+CD25+T세포적수량.결론 RAPA기가유도면역내수,발휘면역억제작용,우가통과백서직접파배이도종이가중T1DM대사문란화병발증.
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. 　