红景天苷对胰岛β细胞保护作用研究及机制探讨
Study on Protective Effects of Salidrosides on Pancreatic β-Cell Survival
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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）150mg/kg建立小鼠糖尿病模型，红景天苷剂量为100mg/kg，每日1次灌胃给药，每5日检测小鼠空腹血糖， 30d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3d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 150mg/kg freshly prepared STZ with citrate buffer as control. The salidroside intervention with a dosage of 100mg/kg/d was initiated on the 8th day after STZ injection and conducted for 30d. Fasting blood glucose levels were measured every five days. After 30d treatment， the oral glucose tolerance test(OGTT) was performed， and blood samples were collected to detect plasma insulin concentrations. The isolated mouse islets were cultured with salidroside(50μmol/L) or DMSO for 3d. Ki67 staining and TUNEL assay were performed to investigate the effects of salidroside on β-cell proliferation and apoptosis. Meanwhile， the mRNA levels of insulin，Pdx-1，GLP-1R and IL-1β in 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 of β-cell was remarkably increased by salidroside， 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-1β which is a cytokine involved in β-cell apoptosis was down-regulated by salidroside. CONCLUSION The present study demonstrates that salidroside can ameliorate the hyperglycemia in STZ diabetic mice by protecting β-cell survival with increased β-cell proliferation and decreased β-cell apoptosis.
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Keywords:
- salidroside /
- diabetes /
- pancreatic β-cell /
- proliferation /
- apoptosis
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