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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。
Objective To study the effect and mechanism of rapamycin on type 1 diabetes mellitus (T1DM) mice. Methods T1DM model was established by intraperitoneal injection of 40 mg / kg STZ into C57BL / 6 mice for 5 days. Normal and T1DM mice were injected intraperitoneally with 2 mg / kg RAPA for 2 weeks. The blood glucose, body weight, food intake and water intake were monitored. Insulitis was observed, the ultrastructure of major organs and the occurrence of apoptosis and autophagy were observed. Th1 / Th2 population and regulatory T cells were detected in spleen. Results RAPA had no obvious effect on the general characteristics of normal mice and the ultrastructure of major organs. But could increase blood glucose, weight loss, feed intake and water intake of T1DM mice (P <0.05), and aggravate the degree of insulitis; induce the autophagy or apoptosis of the pancreas, kidney, spleen and thymus LC3, Beclin1, Caspase-3 expression increased; Th1 cells in normal and T1DM mice were reduced, Th2 cells were increased, and the number of CD4 ~ + CD25 ~ + T cells was increased. Conclusion RAPA can induce immune tolerance, play an immunosuppressive role, but also directly destroy the islets by autophagy to aggravate T1DM metabolic disorders and complications.