Experimental Study On Aberrant Lipid Metabolism Of PBMC From SLE And Regulation Mechanism(s) Of Oligomric Proantho Cyanidins

Objective The aberrant lipid metabolism is one of the major factors that lead to the dysfunction of lymphocytes in SLE patients.Experimental study on lipid alteration(s)in peripheral blood mononuclear cells(PBMC)from SLE patients with multidimensional mass spectrometry-based shotgun lipidomic(MDMS-SL)technology could promote understanding of pathological mechanism(s)for abnormal proliferation and dysfunction of lymphocyte subsets;Analyses the changes of these altered lipid species and immuno-inflammatory responses of PMBC with the treatment of oligomric proantho cyanidins(OPC-3)have been performed to disclose the related mechanism(s).Therefore,this study could uncover underpinning mechanism(s)for translational/precision medicine under treatment with TCM intervention.Methods The lipidomes from 33 individuals of SLE and year-and sex-matched normal people were analyzed using MDMS-SL method.After cultivated 12 h,the levels of IL-10,anti-phospholipid antibodies in the clear supernatant of live PBMC from the normal and the SLE treated with glucocorticoids and OPC-3 were measured with ELISA.Moreover,the PBMC collected from different group were subjected to lipidomics analysis to find the alterations of these observed-changed lipids in SLE patients.Results 15 types of lipid classes(about 149 species)in PBMC from normal and SLE were analyzed with MDMS-SL platform.the results suggested that,in compared with the normal,the total content of pPE in SLE decreased by 18%(p<0.05);the total concentrations of HNE and lysophospholipids(e.g.,LPC and LPE)were elevated by～70%(p<0.001),～147%(p<0.001)and 60%(p<0.001),respectively.Moreover,the total level of PS increased from 4.79±0.19 in normal to 5.44±0.23 nmol/mg protein in SLE patient(p<0.05).There were no significant differences in alteration of other lipid classes.After treated with glucocorticoids and OPC-3,the cytokines IL-10 and self-antibodies(i.e.,anti-dsDNA antibody,anti-cardiolipin antibody,and anti-phospholipid antibody)in clear supernatant and the changed lipid classes in SLE PBMC were almost corrected to the normal.Conclusion the alterations of lipid classes including decreased content of pPE and elevated HNE,lysophospholipid and end-products of lipid peroxidation HNE revealed by MDMS-SL suggested that increased oxidative stress exited in SLE PBMC.Meanwhile,the aberrant of lipid metabolism also could be used to interpret the dysfunction and abnormal immuno-inflammatory response of lymphocytes.After treated with natural antioxidative substance OPC-3,the changed lipid metabolism in PBMC was largely corrected,and immuno-inflammatory response was also regulated.The result suggested that the antioxidative substances in TCM may play key roles in clinical treatment of SLE.Moreover,the result further demonstrated that the aberrant lipid metabolism of PBMC is one of the main factors for the dysfunction of lymphocytes.