Betatrophin对1型糖尿病小鼠胰岛β细胞功能的保护作用研究

Protective effect of betatrophin on islet β-cell function in T1DM mice

目的探究胰岛再生激素(betatrophin)对1型糖尿病(T1DM)小鼠胰岛β细胞功能的保护作用。方法选取135只小鼠,随机数字表法分为对照组、模型组、干预组各45只。模型组、干预组持续5 d腹腔注射链脲佐菌素溶液制备T1DM小鼠模型,对照组不做任何处理,干预组建模成功即刻经尾静脉注射betatrophin过表达腺病毒。分析各组胰岛β细胞免疫组化染色情况,并比较三组小鼠betatrophin蛋白水平、胰岛素释放试验结果及糖代谢指标、脂代谢指标。结果干预组betatrophin蛋白水平明显高于模型组、对照组(P<0.05);干预组PAS染色可见胞浆内紫红色,而模型组无紫红色染色;干预组、模型组T1DM建模成功后胰岛β细胞体积、产物数量较对照组明显小,干预组干预后胰岛β细胞染色强度明显小于模型组,但产物数量较模型组多;干预组、对照组注射胰岛素后0 min、30 min、60 min、90 min、120min血糖水平明显低于模型组(P<0.05),即干预组血糖对胰岛素敏感性大于模型组;与模型组比较,干预组、对照组空腹血糖、空腹胰岛素、2 h血糖、2 h胰岛素、总胆固醇(TC)、甘油三酯(TG)、血清总胆固醇(TC)、低密度脂蛋白(LDLC)明显降低,高密度脂蛋白(HDL-C)明显升高,差异有显著性(P<0.05)。结论Betatrophin可有效保护T1DM小鼠胰岛β细胞功能并促进胰岛素分泌,在提高小鼠对胰岛素敏感性及调节糖脂代谢方面有积极作用,或可为T1DM新型治疗策略提供参考。

Objective To explore protective effect of betatrophin on isletβ-cell function in mice with type 1 diabetes mellitus(T1 DM).Methods 135 mice were divided into control group,model group and intervention group by random number table method,45 cases in each group.In model group and intervention group,5 d intraperitoneal injection of streptozotocin was performed to prepare T1 DM mouse models,the control group was not given any treatment.Immediately after successful modeling in intervention group,betatrophin overexpression adenovirus was injected by tail vein.The immunohistochemical staining of isletβcells in each group was analyzed.The betatrophin protein level,insulin release test,glucose metabolism indexes and lipid metabolism indexes were compared between model group and intervention group.Results The level of betatrophin protein in intervention group was significantly higher than that in model group and control group(P<0.05).PAS staining showed that there was prunosus inside endochylema in intervention group,while there was no prunosus staining in model group.After successful T1 DM modeling,volume of isletβ-cells and number of products in intervention group and model group were significantly less than those in control group.After intervention,intensity of isletβ-cell staining in intervention group was significantly lower than that in model group,while number of products was more than that in model group.At 0 min,30 min,60 min,90 min,and 120 min after insulin injection,blood glucose level in intervention group and control group was significantly lower than that in model group(P<0.05).The glucose sensitivity to insulin in intervention group was greater than that in model group.Compared with model group,fasting blood glucose,fasting insulin,2 h blood glucose,2 h insulin,TC,TG and LDLC were significantly lower in intervention and control group,while HDLC was significantly higher(P<0.05).Conclusion Betatrophin can effectively protect isletβ-cell function and promote insulin secretion in T1 DM mice,which plays positive roles on increasing insulin sensitivity and regulating glucose-lipid metabolism.And it may provide reference for new treatment strategies of T1 DM.