基于多维质谱“鸟枪法”探讨运脾和络方对2型糖尿病大鼠骨骼肌脂肪异位沉积的影响

Effects of Yunpi Heluo Formula on skeletal muscle ectopic fat deposition of T2DM rats based on multi-dimensional mass spectrometry-based shotgun lipidomics

目的:探讨运脾和络方对2型糖尿病(T2DM)大鼠骨骼肌脂肪异位沉积的影响。方法:采用高脂饲料喂养ZDF大鼠建立T2DM模型,将大鼠随机分为模型组和运脾和络组,另设正常组普通饲料喂养。干预10周后检测各组大鼠体质量、空腹血糖及脂质含量,观察各组大鼠骨骼肌病理改变,并运用多维质谱"鸟枪法"脂质组学技术进一步进行模式判别,分析各组大鼠骨骼肌脂质代谢的变化,筛选潜在生物标记物并进行代谢物网络分析。结果:与正常组比较,模型组大鼠体质量增加,血糖升高,脂质含量升高(P<0.01,P<0.05),病理观察显示脂肪沉积;与模型组比较,运脾和络组大鼠体质量减轻,血糖下降,脂质含量有不同程度下降,病理观察显示脂肪沉积改善。脂质组学通过采用有监督式方法OPLS-DA进行建模分析,筛选并鉴定出14个生物标记物,运脾和络可回调各生物标记物的异常改变。结论:运脾和络方可改善T2DM大鼠骨骼肌脂肪异位沉积,其机制可能与改善骨骼肌线粒体功能和调节脂肪酸代谢及磷脂代谢有关。

Objective:To investigate the effect of Yunpi Heluo Formula(YPHL)on skeletal muscle ectopic fat deposition of type 2 diabetes mellitus(T2DM)rats.Methods:ZDF rats were fed with high fat diet to establish a T2DM model.The rats were randomly divided into model group and YPHL group,and the control group were fed with normal diet.The body weight,fasting glucose,lipid content in each experimental groups were tested and pathological changes of skeletal muscle were observed after ten weeks.In addition,we made mode discrimination and analyzed lipid metabolism changes to screening potential biomarkers and make metabolite network analysis in each group by multi-dimensional mass spectrometry-based shotgun lipidomics.Results:Compared with the normal group,the weight,blood glucose and lipid content increased in model group(P<0.01,P<0.05)and pathological observation showed steatosis and deposition in skeletal muscle;compared with the model group,the above index were improved in YPHL group.Fourteen biomarkers were screened and identified by OPLS-DA.The abnormal changes of each biomarker could be adjusted by YPHL.Conclusion:YPHL can improve the ectopic deposition of skeletal muscle fat in T2DM rats by improving skeletal muscle mitochondrial function and regulating fatty acid and phospholipid metabolism.