目的:观察糖肾方对自发性2型糖尿病模型(OLETF)大鼠脂代谢及肝脏脂变的作用,探讨相关的作用机制。方法:45只雄性OLETF大鼠随机分成OLETF组、糖肾方组(1.60g/kg)和蒙诺组(0.833mg/kg)。18只LETO大鼠作为正常组。各实验组从动物12周龄起开始给药。分别在36周龄和56周龄取材,检测血脂水平,观察肝组织病理组织学变化并进行半定量分析,逆转录聚合酶链式反应(RT-PCR)分析SREBP-1及G6PDmRNA在肝组织中的表达。结果:糖肾方能显著降低OLETF组大鼠总胆固醇(TC)水平(P〈0.01),减轻肝脂病变,显著改善肝脏组织大、小空泡的发生面积(P〈0.05);抑制SREBP-1mRNA在肝脏中的表达(P〈0.05);上调G6PDmRNA在肝脏中的表达(P〈0.001)。结论:糖肾方可以改善OLETF大鼠的血脂水平异常及肝脂变,其可能的机制是通过降低SREBP-1和增加G6PDmRNA在肝脏的表达,减少脂肪在肝脏中的淤积及降低TG的合成。
Objective: To study the effects of Tangshen Formula (TSF) on lipid metabolism and hepatic steatosis on Otsuka Long-Evans Tokushima Fatty (OLETF) Rats and investigate the mechanism. Methods: OLETF rats were randomly divided into model group, TSF group (1.60g/kg) and Monopril group (0.833mg/kg). 18 male Long-Evans Tokushima Otsuka (LETO) rats were used as control group. All animals were administered at 12 weeks of age, and sacrificed at 36 and 56 weeks of age respectively. The serum levels of lipids were measured, hepatic pathology were observed, and the mRNA expression of SREBP-1 and G6PD by RT-PCR were examined. Results: Compared with control group, the serum level of total cholesterol (TC) in model group was significantly higher at 56 weeks of age(P0.01), and the serum levels of triglyceride (TG) in model group were also significantly increased at 36 and 56 weeks of age. TSF could significantly decreased serum level of TC of OLETF rats, importantly, the histological evaluation of rat liver demonstrated that TSF reduced lipid accumulation of OLETF rats. RT-PCR revealed that TSF decreased the mRNA expression of SREBP -1 and G6PD in the liver of OLETF rats(P0.001). Conclusions: TSF could rectify disorder of lipid metabolism and improve hepatic steatosis of OLETF Rats, and its mechanisms may be related to inhibit the expression of SREBP-1 and G6PD mRNA in liver.