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。%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 AUGINSO-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.
展开▼
