喂食槲皮素对Ⅰ型糖尿病大鼠的生化及血浆代谢组学研究

Biochemical and Plasma Metabolomics of Quercetin Feeding Rats with Type I Diabetes

目的:探究喂食槲皮素对链脲佐菌素诱导的Ⅰ型糖尿病大鼠的治疗效果及引起的代谢通路变化。方法:采用腹腔注射链脲佐菌素60 mg/kg建立Ⅰ型糖尿病大鼠模型,随机分为模型(T1DM)组、槲皮素低剂量(T1DM+QUE(25))组、槲皮素高剂量(T1DM+QUE(50))组。治疗组给予相应浓度的槲皮素(mg/kg),正常对照组(Normal)与T1DM组给予与治疗组相应体积的空白溶剂,持续喂养8周后收集血样进行乙酰乙酸、糖化血红蛋白、丙氨酸氨基转移酶、血脂等检测,收集肌肉组织样品检测糖原合成酶水平。并以LC-MSMS进行血浆代谢组学分析。结果:与T1DM组相比,T1DM+QUE(50)组血浆中的乙酰乙酸、天门冬氨酸氨基转移酶水平显著降低(P<0.05),脂蛋白脂酶、总抗氧化能力水平显著上升(P<0.05),其水平相较T1DM组更接近Normal组,而糖化血红蛋白、丙氨酸氨基转移酶、低密度脂蛋白、总胆固醇水平也有一定改善,但不显著;肌肉中的糖原合成酶蛋白表达亦有显著改善(P<0.05)。代谢组学分析结果显示槲皮素喂食主要干预鞘脂的代谢与合成、类固醇激素生物合成、视黄醇代谢、花生四烯酸代谢等代谢通路。结论:槲皮素喂食可改善Ⅰ型糖尿病大鼠脂质及胆固醇代谢,缓解肝损伤,通过影响脂质代谢及调节炎症相关通路而达到一定的治疗效果。

Objective:To investigate the therapeutic effects of feeding quercetin on streptozocin-induced type 1 diabetic rats and the associated metabolic pathway changes.Methods:Type 1 diabetic rat models were established by intraperitoneal injection of streptozotocin at a dose of 60 mg/kg.Rats were randomly divided into the model(T1DM)group,quercetin low-dose treatment(T1DM+QUE(25))group,and quercetin high-dose treatment(T1DM+QUE(50))group.The treatment groups were given quercetin at the corresponding concentrations(mg/kg),while the normal control group(Normal)and the T1DM group were given an equivalent volume of blank solvent.After 8 weeks of continuous feeding,plasma samples were collected for the detection of acetoacetic acid,glycosylated hemoglobin,alanine aminotransferase,and blood lipids.Muscle tissue samples were collected to measure glycogen synthase levels.Plasma metabolomics analysis was performed using LC-MS/MS.Results:Compared with that in the T1DM group,acetoacetic acid,aspartate aminotransferase in plasma in the T1DM+QUE(50)group decrease(P<0.05),while total antioxidant capacity levels in lipoprotein lipase increased(P<0.05),and their levels were closer to Normal group than T1DM group.The levels of glycosylated hemoglobin,alanine aminotransferase,low-density lipoprotein and total cholesterol were also improved,but not significantly.The expression of glycogen synthase protein in muscle was also significantly improved(P<0.05).Metabolomics analysis results showed that quercetin feeding mainly interfered with sphingolipid metabolism and synthesis,steroid hormone biosynthesis,retinol metabolism,arachidonic acid metabolism and other metabolic pathways.Conclusions:Feeding quercetin can improve lipid and cholesterol metabolism in type 1 diabetic rats,alleviate liver damage,and achieve certain therapeutic effects by influencing lipid metabolism and modulating inflammation-related pathways.