Study On The Aberrant Metabolism Of Renal Lipid In The Pathogenesis Of Lupus Nephritis And The Regulation Mechanism Of Jieduquyuziyin Decoction

Objective To analyze the changes of lipid in renal tissue of MRL/lpr lupus mice and MRL/MPJ mice in early disease state and after treatment with Chinese and prednisone,and to explore the changes of early lipid biomarkers in combination with relevant serum indexes and pathological results,so as to reveal the possible pathogenesis of lupus kidney.Objective to analyze the changes of lipid biomarkers in early stage of MRL/lpr lupus erythematosus and normal MRL/MPJ mice by means of multi-dimensional mass spectrometry "shotgun" liposome(MDMS-SL).At the same time,it provides new possible ideas and new research directions for clinical treatment,through different treatment measures,to explore the abnormal lipid metabolism in different periods and different treatments,and try to find new targets of treatment intervention.Methods MRL/MPJ mice aged 4 weeks were selected as blank control group,and female MRL/lpr lupus mice of the same week were selected as model group and experimental group.MRL/lpr lupus mice were randomly divided into 3 groups(model group,prednisone group and traditional Chinese medicine group)and were given different intervention measures.After 2 weeks of adaptive feeding,the mice were given drugs,and the mice were killed 2 weeks and 8 weeks later.The relevant biological samples were collected and the urine protein of mice was determined.The level of inflammatory factors in serum of mice was detected by ELISA.The one kidney was fixed with paraformaldehyde.After dehydration and fixation,paraffin sections were made,HE staining and immunohistochemical staining were used to observe the changes of kidney tissue.The left kidney was made into tissue homogenate by ultrasonic pulverization after grinding tissue,and the lipids were extracted by chloroform/methanol solvent system.The lipid extract was analyzed by MDMS-SL technology,and the differences of lipid molecules in the model group,the experimental group and the control group were compared.Results 1.Even as a classical model of lupus mice,compared with MRL/MPJ mice,MRL/lpr had no lupus symptoms,no Inflammatory cells infiltration and abnormal immune complex deposition in the early stage(8 weeks old).For 14-week-old mice,there were significant differences in urinary protein level and inflammation level between the model group and the blank group.There has been infiltration of Inflammatory cells and abnormal deposition of immune complexes.2.MDMS-SL technique was used to analyze many kinds of lipid molecules in renal tissue of each group,among which six kinds of lipid molecules PS,SM,CER,LPE,ST and HNE were analyzed qualitatively and quantitatively.There are also differences in kidney-related lipids in 8-week-old mice,and this difference may further lead to the progression of the disease,and the difference in kidney in 14-week-old mice is greater than that in 8-week-old mice.The changes of the contents of PS,SM,CER,LPE,ST and HNE lipids in the model group meant that the oxidation level of the body increased.3.The effects of prednisone and Luangchuangding on the improvement of lipids were not the same,except for the effect of LPE,the other five kinds of lipids were significantly improved.However,the two have different effects on regulating lipids.Traditional Chinese medicine has a greater effect on regulating PS,ST and CER in the early stage,and almost the same effect on the regulation of HNE and SM.The intervention of early use of traditional Chinese medicine may be better to reduce the symptoms of lupus nephritis.Conclusion 1.The biochemical level and pathological state of lupus mice are different between 8-week-old and 14-week-old lupus mice.The 14-week-old mice have shown significant pathological changes of LN.2.Lipids are closely related to the condition of lupus kidney.Abnormal lipid metabolism will aggravate cell apoptosis,affect the level of oxidative stress,and aggravate the symptoms and condition of LN.Prednisone or Luangchuangding may improve the disease state of LN by regulating lipid metabolism,improving the physiological state of cells,reducing the level of oxidative stress and reducing inflammation.