The Experimental Study Of Postponed Effect Of All-Trans Retinoic Acid On Glomerulosclerosis

PartⅠAIM:To study the postponed effects of all-trans retinoic acid(ATRA)on experimental glomerulosclerosis in rats.METHODS:Eighty Wistar male Rats(eitht-week-old)were randomly assigned into following groups:sham operated group(A group,n=20),model group(B group,n=20),benazepril treatment group(C group,n=20),ATRA treatment group(D group,n=20).Rats in A group was subjected to sham operation and injected with normal saline after one week through the tail vein.Rats in other groups were uninephrectomized and injected with adriamycin(5 mg·kg^-1)after one week through the tail vein.Then the rats in C group were administered orally by benazepril(10mg·kg^-1·d^-1)and the rats in D group were administered orally by ATRA(20mg·kg^-1·d^-1),rats were killed at the 12th week.Giving normal saline of the equal volume to the rats in A group and B group.At 0,12 weeks,we measured serum total protein(TP)and albumin(Alb),serum creatinine(Scr),blood urea nitrogen(BUN).At 0,3,5,7,9 and 12 weeks,we Collect the 24-hour urine of the rats from each group which were placed individually in metabolic cages.Routine HE staining for Kidney morphology and glo- merulosclerosis was evaluated by glomerulosclerosis index system.RESULTS:Compared to A group,The urinary protein,Scr,BUN and glomerular sclerosis were significantly increased in B group(P＜0.05). Compared to B group,C and D group's 24 hour urinary protein,BUN,glomerular sclerosis were significantly reduced(P＜0.05,respectively),ATRA could significantly reduce Scr compared with B group(P＜0.05).C and D group had no significant difference in urinary protein,BUN and glomerular sclerosis(P＞0.05,respectively),but they had significant difference in Scr(P＜0.05).CONCLUSION:ATRA can delay the development of chronic glomerulosclerosis in rats.PartⅡAIM:To analyze the mechanism of ATRA regulating the production and degradation of extracellular matrix(ECM).METHODS:Eighty Wistar male Rats(eitht-week-old)were randomly assigned into following groups:sham operated group(A group,n=20),model group(B group,n=20),benazepril treatment group(C group,n=20),ATRA treatment group(D group,n=20).The establishiment of model and renal tissue sampling were the same as that in part one.Immunohistochemistry was performed on renal tissue to detect CollagenⅣ(ColⅣ),fibronectin(FN),transforming growth factor-β1(TGF-β1)andα-smooth muscle actin(α-SMA)which was a cyto- skeletal marker of myofibroblast.Reverse TranScription Polymerase Chain Reaction(RT-PCR)was used to examine the expression levels ofα-SMA mRNA in the renal tissue.RESULTS:Immunohistochemistry staining indicated that increased ColⅣ, FN,TGF-β1 andα-SMA expression in B group compared to A group(P＜0.05, respectively).RT-PCR showed The expression level ofα-SMA mRNA in the model group was obviously higher than that in A group(P＜0.05).Compared to B group,all of those indexes in C and D group were significantly reduced (P＜0.05,respectively),there was no significant difference between C and D group(P＞0.05).CONCLUSION:ATRA has a beneficial effect on retarding the progression of experimental glomerulosclerosis in rats,possibly through down- regulating the expression of TGF-β1,inhibit the transdiferenti-ation of glomerular primary cells and decreasing the synthesis of ColⅣand FN.