| BackgroundLupus nephritis(LN)is one of the most common and most serious complications of systemic lupus erythematosus(SLE),and its treatment determines the quality of life and prognosis of patients.Cyclophosphamide has been shown to be effective in improving and controlling the progression of LN in animal models and clinical treatments,known as the treatment of LN milestones.But because of its bone marrow suppression,gonadal suppression,infection,malignant tumors and other side effects,so that its application subject to certain restrictions.So it is an important research direction to find a drug that is more effective or similar in efficacy to cyclophosphamide and is well tolerated.All-trans retinoic acid(ATRA)is the active metabolite of vitamin A and is currently used clinically in the treatment of acute promyelocytic leukemia and is widely used in the treatment of solid tumors such as thyroid cancer,breast cancer,small cell lung cancer And prevention,is commonly used in clinical differentiation inducer.But the Medline search has not yet seen the clinical report on the treatment of LN,there is no treatment with the classic drug cyclophosphamide treatment of LN compared the report.In recent years,retinoic acid in many kidney disease animal model showed better immune regulation and renal protection,ATRA has blocked kidney fibrosis,reduce glomerular hypertrophy,protect the function of the kidney.Retinoic acid may be a new method for the treatment of kidney disease,providing new ideas for the prevention and treatment of LN..ObjectiveThe effects of cyclophosphamide and all-trans retinoic acid on the expression of MRL / lpr in mice with lupus nephritis were observed after mouse anti-dsDNA antibody,serum creatinine(Scr),blood urea nitrogen(BUN),plasma alanine aminotransferase(ALT),serum albumin(ALB),urinary creatinine(Ucr),Histomorphological changes and expression of TGF-?1 and MCP-1 protein and m RNA in renal tissue.To compare the therapeutic effect of cyclophosphamide and all-trans retinoic acid in the model of MRL / lpr in lupus nephritis mice,and to explore whether the protective effect of cyclophosphamide and all-trans retinoic acid on renal structure and function during the course of LN difference.MethodsThe MRL / lpr mice were randomly divided into 3 groups: ATRA group(10mg · Kg-1 · d),model group(10mg · Kg-1 · d),cyclophosphamide group(100mg · Kg-1 · d),Each group of 6,CTX group intraperitoneal injection,continuous administration of two days,the other two groups daily intragastric administration 8 weeks after the death.After the end of the experiment,mice were collected with blood samp.Blood Urea Nitrogen(BUN),Serum creatinine(Scr),serum albumin(ALB),serum total protein(STP),plasma Alanine transaminase(ALT),anti-double stranded DNA antibody(dsDNA).(TGF-?1)and monocyte regulatory protein(MCP-1)in the kidney of mice were detected by immunohistochemical method.The changes of renal tissue structure were observed by Periodic Acid-Schiff stain(PAS)And the expression of TGF-?1 MCP-1 in renal tissue was analyzed by semi-quantitative analysis using protein-pro Plus software.real-time fluorescent quantitative PCR(RT-qPCR)was used to detect the mRNA expression of TGF-?1 and MCP-1 in renal tissues.SPSS19.0 software was used for statistical analysis.The results of measurement data were expressed as mean ± standard deviation.There was a single factor analysis of variance between the two groups.The t test was used to compare the two groups.The test level was ? = 0.05.ResultsCompared with the model group,ATRA treatment group and CTX treatment group BUN,Scr and Ucr blood indexes of renal function were decreased,compared with statistical difference(P<0.05),blood ALT,blood ALB,serum dsDNA antibody titers wereof no significant difference between the three groups.The levels of TGF-1,MCP-1 protein and mRNA in renal tissue of CTX treatment group were significantly lower(P<0.05).The levels of TGF-beta,MCP-1 protein and mRNA were significantly lower in ATRA treated mice(P<0.05).The BUN,Scr and Ucr levels of TGF-,mRNA protein and MCP-1 in renal tissue of CTX treated group were significantly lower than those of ATRA group(P<0.05).Conclusions1.Cyclophosphamide(CTX)and all trans retinoic acid(ATRA)and exenatide can decrease the levels of BUN and Scr in LN mice and decrease the expression of TGF-?1and MCP-1 protein in renal tissue and delay the development of lupus nephritis2.In mice with lupus nephritis,cyclophosphamide and all trans retinoic acid were used to improve renal function;3.All trans retinoic acid has the function of anti inflammation,inhibiting fibrosis and protecting renal function,which provides a basis for clinical use of ATRA in the treatment of lupus nephritis... |
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