红景天苷对胰岛β细胞保护作用研究及机制探讨

摘要

目的：考察红景天苷的降糖功效及其对胰岛β细胞的保护作用。方法采用 C57BL/6小鼠一次性注射链脲佐菌素(STZ)150 mg/kg 建立小鼠糖尿病模型,红景天苷剂量为100 mg/kg,每日1次灌胃给药,每5日检测小鼠空腹血糖,30 d 后检测小鼠胰岛素水平并进行口服糖耐量实验(OGTT)。同时分离正常小鼠胰岛培养3 d 后,通过 Ki67免疫荧光染色及 TUNEL染色方法考察红景天苷(50μmol/L)对胰岛β细胞增殖与凋亡的作用。通过 RT-PCR 方法检测β细胞增殖相关基因 insulin、Pdx-1、GLP-1R、IL-1β转录水平变化。结果与 STZ 组相比较,红景天苷组(STZ/Sal)能够有效降低小鼠空腹血糖,并表现出胰岛素水平增加的趋势,其 OGTT 实验也得到显著改善。而小鼠胰岛染色实验表明,红景天苷可以明显促进β细胞增殖,减少高糖诱导的β细胞凋亡。并且红景天苷促进 insulin、Pdx-1、GLP-1R 等基因的 mRNA 水平升高,降低炎症因子 IL-1β的mRNA 水平。结论本研究证实红景天苷有效保护胰岛β细胞,促进β细胞增殖并抑制其凋亡,从而实现降低血糖的作用。%ABSTRACT:OBJECTIVE To investigate the hypoglycemic action and β-cell protective effect of salidroside in streptozotocin (STZ) induced diabetic mice and cultured mouse islets.METHODS C57BL∕6J mice were injected with a single dose of 1 50 mg∕kg freshly prepared STZ with citrate buffer as control.The salidroside intervention with a dosage of 100 mg∕kg∕d was ini-tiated on the 8th day after STZ injection and conducted for 30 d.Fasting blood glucose levels were measured every five days. After 30 d treatment,the oral glucose tolerance test(OGTT)was performed,and blood samples were collected to detect plas-ma insulin concentrations.The isolated mouse islets were cultured with salidroside(50 μmol∕L) or DMSO for 3 d.Ki67 stai-ning and TUNEL assay were performed to investigate the effects of salidroside on β-cell proliferation and apoptosis.Mean-while,the mRNA levels of insulin,Pdx-1,GLP-1R and IL-1βin islets were detected by RT-PCR.RESULTS Compared with the STZ group,salidroside displayed significantly hypoglycemic effects,together with increased plasma insulin contents as well as improved OGTT.The Ki67 staining in cultured islets showed the proliferation ofβ-cell was remarkably increased by salidro-side,while the β-cell apoptosis induced by high glucose was strongly inhibited by salidroside.Moreover,the mRNA levels of insulin,Pdx-1 and GLP-1R were up-regulated by salidroside significantly.However,the mRNA level of IL-1βwhich is a cyto-kine involved inβ-cell apoptosis was down-regulated by salidroside.CONCLUSION The present study demonstrates that sali-droside can ameliorate the hyperglycemia in STZ diabetic mice by protecting β-cell survival with increased β-cell proliferation and decreasedβ-cell apoptosis.