梓醇对糖尿病小鼠肝肾并发症与肝脏胆汁酸作用的研究

Effect of Catalpol on Hepatic and Renal Complications and Hepatic Bile Acid in db/db Mice

目的:考察梓醇对2型糖尿病小鼠糖代谢及其胆汁酸水平的影响。方法:取高糖高脂饲料喂养的实验用糖尿病纯合子(db/db)小鼠作为2型糖尿病模型,随机分为模型组、阳性药组和梓醇低剂量组、梓醇中剂量组、梓醇高剂量组,以糖尿病导入m基因杂合子(db/m)小鼠作为正常组,给药8周后,检测小鼠体质量、血糖、肝功能及视网膜病理变化,并利用超高效液相色谱法-三重四极杆-线性离子阱质谱(UPLC-QTRAP-MS/MS)分析肝脏胆汁酸水平。结果:与模型组比较,梓醇显著控制db/db小鼠体质量并降低其血糖、糖耐量、血清谷丙转氨酶(GPT)、谷草转氨酶(GOT)、总胆红素(T-Bil)、血清白蛋白、直接胆红素(D-Bil)和间接胆红素(I-Bil)水平,且有效降低脏器系数(P<0.05)及改善肝脏和视网膜损伤;同时发现,梓醇与二甲双胍显著降低糖尿病小鼠肝脏中的熊去氧胆酸(UDCA)水平(P<0.05),且提高了小鼠肝脏中的石胆酸(LCA)、脱氧胆酸(DCA)与鹅去氧胆酸(CDCA)水平(P<0.05)及叶酸(FA)、维生素B_(12)的水平。结论:梓醇能通过调节肝脏胆汁酸水平来调节2型糖尿病小鼠的糖代谢,改善肝脏和视网膜损伤,并降低周围神经病变的风险。

Objective:To investigate the effects of catalpol on glucolipid metabolism and its complications in type 2 diabetic db/db mice.Methods:The db/db mice were taken as a model of type 2 diabetes and randomly divided into model group,metformin group(positive)and catalpol low-,medium-and high-dose groups.The db/m mice were used as control group.After 8 weeks of treatment,the rat body weight,blood glucose,liver function,and retinal changes were detected,and hepatic bile acid was determined using ultra-performance liquid chromatography-quadrupole linear ion trap mass spectrometry(UPLC/Q-TRAP/MS).Results:Compared with the conditions in model group,catalpol regulated body weight,reduced blood glucose,improved glucose tolerance,decreased levels of serum alanine aminotransferase(GPT),glutamic oxaloacetic aminotransferase(GOT),total bilirubin(T-Bil),albumin(ALB),direct bilirubin(D-Bil)and indirect bilirubin(I-Bil)in db/db mice and their organ coefficient(P<0.05),and ameliorated liver and retinal damage.It was also found that catalpol and metformin down regulated the level of ursodeoxycholic acid(UDCA)(P<0.05)and up regulated the levels of lithocholic acid(LCA),deoxycholic acid(DCA)and chenodeoxycholic acid(CDCA)(P<0.05)as well as the contents of folic acid(FA)and vitamin B12(VB12)in the liver of diabetic mice.Conclusion:Catalpol may regulate glucose metabolism in type 2 diabetic mice by regulating hepatic bile acid,improving liver and retinal damage and lowering the risk of peripheral neuropathy.