大黄酸对db/db小鼠胰岛功能及炎症氧化损伤标志物表达的影响

Effects of rheinic acid on markers of insulin secretion, inflammation and oxidative injury in db/db mice

目的通过先天性2型糖尿病动物模型db／db小鼠，探讨大黄酸对胰岛功能及炎症、氧化损伤标志物表达的影响。方法选取30只4周龄db／db雄性小鼠，随机分成治疗组和对照组，每组15只。治疗组每日固定时间给予大黄酸（120mg／kg，1％纤维素钠溶解）灌胃，对照组给予相同体积的1％纤维素钠，连续给药8周。投药结束后行经腹腔葡萄糖耐量试验（IPGTF）并测定胰岛素水平，用曲线下面积（AUG）代表胰岛素分泌水平，并通过计算IPGTT的0—30min胰岛素AUC评估早期胰岛素分泌功能。同时对小鼠胰腺进行胰岛素、核因子．KB（NF—KB）及8．羟基脱氧鸟苷（8-OHdG）免疫组织化学染色。结果与对照组相比，治疗组糖负荷后0，30，60，120min的血糖水平明显下降，而30，60，120min的胰岛素水平明显升高，尤其是早期相胰岛素水平升高更明显。同时，大黄酸治疗组小鼠胰岛素染色明显增强，NF-KB及8-OHdG表达明显受抑制。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，恢复早期胰岛素分泌功能，保护胰岛功能：同时早期大黄酸治疗明显减少炎症、氧化损伤标志物的表达。

Objective To investigate the effects of rheinic acid on markers of early-phase insulin secretion, inflammation and oxidative injury by constructing the congenital type 2 diabetic db/db mice model. Methods Thirty db/db mice at 4 weeks of age were randomly allocated to be treated with rheinic acid （120 mg/kg supplemented with 1% sodium cellulose solution） in treatment group or an aliquot of 1% sodium cellulose in control group （n=15） for 8 weeks. This was followed by intraperitoneal glucose tolerance test （IPGTr） for measurement of early-phase insulin se- cretion based on the area under curve（AUC） at 0-30 min. Immunohistochemical staining was employed to assay the level of insulin, NF-KB and 8-OHdG in the pancreas. Results Compared with control group, the treatment of rheinic acid resulted in substantially reduced blood glucose concentrations at 0, 30, 60 and 120 min yet markedly increased levels of insulin at 30, 60 and 120 min （all P〈0.05）. Meanwhile, the treatment group was characterized by significantly augmented insulin expression yet attenuated expression of NF-KB and 8-OHdG. Conclusion Early-phase adminis- tration of rheinic acid may significantly improve glucose tolerance, restore early-phase insulin secretion and substantially suppress the expression of markers associated with inflammation and oxidative injury, thus protecting the normal pancreatic function in db/db mice.