【摘要】 目的大黄酸(4,5-二羟基蒽醌-2-羧酸)是大黄的蒽醌衍生物之一。本研究旨在通过db/db小鼠这一先天性2型糖尿病动物模型,探讨大黄酸对血糖水平的影响以及对胰岛β细胞的作用。方法 30只4周龄db/db小鼠随机分为两组:对照组(1%纤维素钠,n=15),大黄酸组(120 mg/kg,n=15),给予连续鼻饲灌胃给药8周。投药结束后行经腹腔葡萄糖耐量试验(IPGTT)并测定相应胰岛素水平,其曲线下面积(AUC)分别代表糖耐量和胰岛素分泌水平,并通过计算IPGTT的0 min至30 min胰岛素曲线下面积以评估早期相胰岛素分泌功能。同时行胰岛素免疫组化染色,通过免疫组化染色计算β细胞含量,并用TUNEL法检测胰岛β细胞的凋亡。结果与对照组相比,大黄酸治疗组糖负荷后0,30,60和120 min的血糖水平明显下降,同时30,60和120 min的胰岛素水平明显升高,尤其是早期相胰岛素水平(AUCINS0-30)明显升高。同时大黄酸治疗组胰岛素染色明显增强,胰岛β细胞含量明显增高,凋亡细胞明显减少。结论早期大黄酸治疗可以明显改善db/db小鼠的葡萄糖耐量,恢复早期相胰岛素分泌,并能抑制胰岛β细胞的凋亡,保护胰岛功能。大黄酸的这一作用可能使之成为一种新的预防或治疗2型糖尿病的手段。更多还原

【Abstract】 Objective To investigate the hypoglycemic action of rhein(4,5-dihydroxyanthraquininone-2-carboxylic acid),one of the anthraquininone derivatives isolated from rhubarb,and study its effects on pancreatic beta-cells in db/db mice.Methods Thirty 4-week-old db/db mice were randomized for an 8-week treatment with intragastric administration of rhein(120 mg/kg,n=15) or placebo(1% natrium cellulose solution,n=15).After the treatment,intraperitoneal glucose tolerance test(IPGTT) was performed and the area under curve(AUC) of insulin levels in IPGTT was calculated to evaluate insulin secretory function.The AUCINS0-30 was calculated to evaluate the early-phase insulin secretion.Immunohistochemical staining for insulin was performed to estimate the beta-cell mass,and beta-cell apoptosis was detected using TUNEL assay.Results Compared with the control group,rhein-treated group showed significantly reduced blood glucose concentrations at 0,30,60 and 120 min after glucose load with significantly higher insulin levels at 30,60 and 120 min.The early-phase insulin secretion was also obviously increased.The beta-cell mass was obviously rescued by the 8-week treatment with rhein,which also notably improved the staining intensity of insulin and suppressed beta-cell apoptosis compared with the control.Conclusions Early rhein treatment significantly improves glucose tolerance by restoring the early-phase insulin secretion in db/db mice and inhibiting the apoptosis of the beta-cells,suggesting the potential of rhein as a novel therapeutic agent for type 2 diabetes.更多还原