【摘要】 目的探究雷帕霉素（RAPA）对高脂血症小鼠的治疗效果及其作用机制。方法 60只雄性C57BL/6小鼠随机分为对照组、模型组和RAPA组,每组20只。对照组给予基础饲料喂养,模型组和RAPA组则给予高脂饲料喂养以建立高脂血症小鼠模型。连续喂养6周后,RAPA组小鼠以1 mg·kg^-1·d^-1的剂量腹腔注射RAPA,对照组和模型组小鼠腹腔注射等体积的生理盐水,连续给药4周。采用全自动生化分析仪测定小鼠TC、TG、LDL-C、HDL-C血脂含量;采用Western blot检测小鼠血管内皮细胞mTORC1活性及自噬水平;采用流式细胞仪检测小鼠外周血Th17和Treg细胞表达水平;采用ELISA法检测小鼠血清IL-17、IL-6、IL-10和TGF-β含量。结果与对照组相比,模型组小鼠TC、TG及LDL-C血清含量显著升高（P<0.05）。RAPA组小鼠TC、TG、LDL-C血清含量较模型组显著下降（P<0.05）。模型组小鼠Phospho-S6K1和P62表达水平较对照组明显升高,RAPA组小鼠的Phospho-S6K1和P62表达水平较模型组显著下调（P<0.05）。与对照组相比,模型组小鼠外周血Th17细胞比例及其分泌的IL-17、IL-6血清浓度明显上升,Treg细胞比例及其分泌的IL-10、TGF-β血清浓度明显下降,Th17/Treg细胞比率上升（P<0.05）。与模型组小鼠相比,RAPA组小鼠外周血Th17细胞比例及IL-17、IL-6血清浓度明显下降,Treg细胞比例及IL-10、TGF-β血清浓度显著上升,Th17/Treg细胞比率下降（P<0.05）。结论 RAPA可能通过抑制m TORC1的活化,增强小鼠体内的自噬水平,改善Th17/Treg细胞的免疫失衡,从而调节小鼠体内的血脂代谢。更多还原

【Abstract】 To investigate the therapeutic effect of rapamycin on hyperlipidemia mice and the mechanism, total of 60 male C57 BL/6 mice were recruited and randomly divided into control group, model group and RAPA group,with 20 mice in each group. The control group was given basal feed, and the model group and the RAPA group were fed with high-fat diet to establish a hyperlipidemia mouse model. Six weeks later, the RAPA group was injected intraperitoneally with RAPA at a dose of 1 mg·kg-1·d-1, whereas the control group and the model group were injected with an equal volume of normal saline for 4 weeks. The contents of TC, TG, LDL-C and HDL-C in mice were determined by automatic biochemical analyzer, while Western blot was used to detect mTORC1 activity and autophagy in mouse vascular endothelial cells. The expression levels of Th17 and Treg cells in peripheral blood were detected by flow cytometry. And the contents of serum IL-17, IL-6, IL-10 and TGF-β were detected by ELISA.Compared with the control group, the serum levels of TC, TG and LDL-C in the model group increased significantly(P<0.05). The serum levels of TC, TG and LDL-C in RAPA group were significantly lower than those in model group(P<0.05); the expression levels of Phospho-S6 K1 and P62 in the model group were significantly higher than those in the control group. The expression levels of Phospho-S6 K1 and P62 in the RAPA group were significantly decreased as compared with the model group(P<0.05). Compared with the control group, the proportion of Th17 cells in peripheral blood and the serum levels of IL-17 and IL-6 in the model group significantly were higher(P<0.05). Compared with the control group, the proportion of Treg cells and the serum levels of IL-10 and TGF-beta significantly decreased, and the ratio of Th17/Treg cells significantly increased(P<0.05). Compared with model mice, the percentage of Th17 cells in peripheral blood and the serum levels of IL-17 and IL-6 in RAPA group significantly decreased, the proportion of Treg cells and serum levels of IL-10 and TGF-beta significantly increased in RAPA group, and the ratio of Th17/Treg cells significantly decreased in RAPA group(P<0.05). In conclusion,RAPA may regulate the immune imbalance of Th17/Treg and the autophagy in hyperlipidemia mice by inhibiting mTORC1 activation.更多还原