补中益气丸对早期糖尿病大鼠肝氧化损害及肝糖原作用的机制

目的:研究补中益气丸对STZ糖尿病大鼠肝脏NO3-、ONOO-、MDA、糖原及肝损害的影响及机制.方法:通过2次腹腔注射链脲佐菌素(STZ)制作大鼠糖尿病模型,第1次腹腔注射STZ55mg/kg,第8天行第2次腹腔注射同等剂量STZ.每周大鼠尾尖采血测空腹血糖值,造模成功的SD大鼠随机分为糖尿病组,常规喂养4wk;补中益气丸组给予补中益气丸水溶液,每只大鼠用量为8g/kg,每天1次,连续28d.采用分光光度法测定鼠肝脏ONOO-、MDA、糖原,通过HE染色病理检查和积分系统估计肝损害程度.结果:糖尿病大鼠出现明显的糖尿病症状,肝病理检测发现肝细胞变小,肝窦变窄,肝细胞核变小浅染,肝小叶结构不清,肝索结构紊乱存在充血和少量炎性细胞浸润,尤其在肝1区肝组织MDA、ONOO-水平显著升高,肝糖原显著降低.补中益气丸组大鼠肝细胞、肝细胞核、肝窦、肝索、肝小叶异常及充血和炎症明显改善,糖尿病症状亦明显改善;肝组织MDA、ONOO-水平显著降低,肝糖原显著升高.相关分析发现,肝糖原与MDA、ONOO-、肝细胞索结构紊乱、充血、炎症呈显著负相关,与肝细胞大小、肝细胞核大小、肝血窦大小呈显著正相关;肝组织MDA、ONOO-水平与肝细胞大小、肝细胞核大小、肝血窦大小呈显著负相关,与肝细胞索结构紊乱、充血、炎症呈显著正相关.结论:补中益气丸可能通过改善STZ糖尿病大鼠肝脏氧化应激,改善胰岛素信号通路、激活磷酸酶脱磷酸化活性,进而升高糖原合成酶活性和肝糖原含量,改善肝氧化代谢和肝的氧化损伤.

Effect of Buzhong Yiqi Pill on oxidative damage and glycogen synthesis in the liver of early diabetic rats

AIM:To evaluate the effect of Buzhong Yiqi Pill on the levels of ONOO-,malondialdehyde(MDA),and glycogen,and oxidative damage in the liver of early diabetic rats.METHODS:Diabetes was induced by two intraperitoneal injections of streptozocin(STZ,55 mg/kg):one on day 1 and the other on day 8.Diabetic rats were randomly divided into diabetes group(untreated)and Buzhong Yiqi Pill group(given Buzhong Yiqi Pill 8 g/kg,i.g.for 28 consecutive days).The concentrations of ONOO-,MDA,and glycogen in the liver weredetermined by colorimetric methods,and hepatic pathology was evaluated by hematoxylin and eosin(HE)staining using a scoring system.RESULTS:Diabetic rats developed significant diabetes symptoms,and had obviously decreased level of glycogen and increased levels of MDA and ONOO-in hepatic tissue.Treatment with Buzhong Yiqi Pill significantly increased the level of glycogen,decreased the levels of MDA and ONOO-,and improved diabetes symptoms and histological changes in the liver.A negative correlation was found between the level of glycogen and those of MDA/ONOOand between the level of glycogen and the severity of diabetes symptoms.CONCLUSION:Buzhong Yiqi Pill decreased the synthesis of free radicals in hepatic tissue possibly by promoting the insulin signaling pathway to activate glycogen synthase,increase hepatic glycogen production and improve liver oxidative metabolism and damage.