目的:研究柴黄益肾颗粒干预对糖尿病肾病(DN)大鼠肾脏脂质代谢异常的调节作用。方法:采用单侧肾切除加i.p.链脲佐菌素诱导的方法复制DN大鼠模型,将38只Wistar大鼠分成4组,包括空白组、模型组、模型+柴黄益肾颗粒组、空白+柴黄益肾颗粒组。模型+柴黄益肾颗粒组ig给予0.56 g·kg-1柴黄益肾颗粒,于造模成功后第20周,采集肾皮质样品进行基于超高压液相-四级杆飞行时间质谱联用仪(UPLC-QTOF MS)的脂质组学研究,考察干预前后脂质代谢物组的变化。结果:造模成功第20周时,大鼠肾皮质中多种甘油磷脂酰胆碱、甘油磷脂酰乙醇胺、甘油磷脂酰甘油醇、甘油磷脂酰肌醇、鞘磷脂酰胆碱等都显著下调,而胆固醇酯和甘油三酯则显著上升。柴黄益肾颗粒干预对部分异常脂质代谢表现出明显的改善作用,包括4种鞘磷脂酰胆碱和2种甘油磷脂酰胆碱,即SM(d18∶1/16∶1),SM(C33∶1),SM(C42∶2),SM(C42∶3),PC(36∶4)和PC(42∶10),其相对变化倍数分别为1.38,1.50,1.29,1.23,1.15和1.30。结论:柴黄益肾颗粒干预可以延缓大鼠DN的进展,该机制可能与其对脂质尤其是鞘脂代谢异常的调节有关。
Objective∶ To study the protective effect of Chaihuang Yishen granules on dysregulated lipids metabolism in kidney of rats with diabetic nephropathy(DN).Method: Wistar rats were undergone uninephrectomy and a single intraperitoneal injection of streptozocin(STZ) to induce diabetes,and administratered with 0.56 g·kg-1 Chaihuang Yishen granules.At the end of 20 weeks,renal cortex of rats was removed and UPLC-QTOF MS was used to lipidomic study and to investigate the alterations of abnormal lipidome after administration of Chaihuang Yishen granules.Result: At the end of 20 weeks,multiple species of significantly decreased glycerophosphocholines,glycerophosphoethanolamines,glycerophosphoglycerols,glycerophosphoinositols and sphingomyelins,and clearly elevated cholesterol esters and triglycerides were identified in renal cortex of rats with DN.Among them,several lipid metabolites,such as 2 glycerophosphocholines and 4 sphingomyelins-SM(d18∶ 1/16∶ 1),SM(C33∶ 1),SM(C42∶ 2),SM(C42∶ 3),PC(36∶ 4) and PC(42∶ 10),can be normalized towards their baseline by the intervention of Chaihuang Yishen granules with individually relative fold change: 1.38,1.50,1.29,1.23,1.15 and 1.30.Conlusion: Chaihuang Yishen gruanules can retard the development of DN in rats,which might be associated with its regulation in abnormally expressed lipids,especially sphingomyelins.