Combing DCE-MRI and fatty acid metabolomics to evaluate the function of bone marrow endothelial progenitor cells in diabetic rabbits with critical limb ischemia
Objective:To evaluate bone marrow endothelial progenitor cells(BMEPCs)functions of proximal femur in diabetes mellitus(DM)combined with critical limb ischemia(CLI)rabbits via dynamic contrast enhanced magnetic resonance imaging(DCE-MRI)microvascular permeabilities and fatty acid metabonomics.Materials and Methods:Eighteen rabbits were randomly selected from 36 male New Zealand big ear white rabbits to build DM model rabbits by intravenous injection of alloxan.Among them,12 DM rabbits were successfully modeled and 6 rabbits that failed to be modeled were euthanized.12 DM rabbits and 12 non-DM rabbits underwent right femoral artery ligation as DM combined with CLI(DM+CLI)group and simple CLI group.In the two groups,10 rabbits in each group survived after surgery.Six non-DM rabbits underwent surgery to expose the right femoral artery without ligation as sham operation control(Control)group(n=6)and all survived.DCE-MRI examination of the right proximal femur was performed in each group at week 0 and 4 after operation.The number of peripheral blood endothelial progenitor cells and right proximal femur BMEPCs,migration and angiogenesis function of BMEPCs and bone marrow fatty acid liquid chromatography-mass spectrometry metabonomics were measured at week 4 after operation,as well as bone marrow microvessel density(MVD)calculated.Results:Compared with CLI group and Control group,DM+CLI group presented higher Ktrans,Kep,Ve at week 4 after operation,while MVD of bone marrow decreased(P<0.05).In addition,the contents of palmitoleic acid,the ratio of monounsaturated fatty acid/polyunsaturated fatty acid and activity of stearoyl-CoA desaturase 1 index decreased(P<0.05)and elongase activity index increased(P<0.05).The abilities of mobilization,migration and angiogenesis of BMEPCs were impaired in DM+CLI group(P<0.05).At week 4 after operation,the Ktrans,Kep and Ve of right proximal femur bone marrow,the related indexes of bone marrow fatty acid anabolism were positively correlated with BMEPCs migration and angiogenesis functions(P<0.05).Correlation analysis of DM+CLI group and CLI group was performed,and the mobilization ability of BMEPCs was negatively correlated with Ktrans,Kep and Ve.Conclusions:It is feasible to evaluate BMEPCs functions in DM+CLI rabbits combining DCE-MRI with fatty acid metabonomics,which can provide visual imaging evidence for the pathophysiological mechanism for lipid regulation therapy to improve functions of BMEPCs and prevent amputation.
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