The Expression Of MMPs/TIMPs In MsPGN Rat Renal Tissue And The Effects Of Nourishing Kidney And Ctiving Blood Recipe Of Traditional Chinese Medicine

Objective:Set up mesangial proliferative glomerulonephritis(MsPGN) rat model,to investigate the expression of matrix metalloproteinase(MMP) and tissue inhibitor of matrix metalloproteinase(TIMP)in MsPGN rat renal tissue and the effects of nourishing kidney and activing blood recipe of traditional Chinese medicine to these factors.Affirm the curative effects of the nourishing kidney and activing blood recipe of traditional Chinese medicine in resisting glomerular sclerosis and postponing the course of chronic renal failure.Methods:Chose 54 male rats and separated them into control group,MsPGN group and treated group with nourishing kidney and activing blood recipe of traditional Chinese medicine.Chose,six rats per group at the time of the second,the fourth and the eighth week.The renal tissue sections were treated with HE and PAS stains and were used to the routine pathologic study.Immunohistochemical staining was used to check the expression of MMP-2,TIMP-2,membrance type metalloproteinases-1(MT1-MMP),MMP10,TIMP-1,transforming growth factor-β1(TGF-β1),laminin(LN),collagenⅣ.Flow Cytometry was used to check the protein expression of MMP-2,TIMP-2,MT1-MMP,MMP-3,MMP-10,TIMP-1 and TGF-β1 in rat renal cortex.In situ hybridization in renal cortex was used to detect the mRNA expression of MMP-2,TIMP-2,MMP-10,TIMP-1.And analysed the change of MMP-2'activity in renal tissue.Results:In MsPGN group,following with the disease progressing,the glomerulus grew graduatly,ECM became more and more,the basement membrane of glomerulus was thicker.The immunohistochemical staining showed that the chief positive granules were deposited in glomerulus and renal tubular.Following with the disease progressing,the expressions of MMP-2 and MT1-MMP were lower compared with control group,but in treated group the level was weaker,the expressions of TIMP-2, TGF-β1,MMP-3,10,TIMP-1,collagenⅣand LN were higher compared with control group,but in treated group the level was weaker too.At the fourth and the eighth week,the Flow Cytometry showed that in MsPGN group the FI of MMP-2 was lower compared with control group(P＜0.01 or＜0.05),but in every period the FI of TIMP-2 and TGF-β1 was higher,and of MT1-MMP was lower compared with control group(P＜0.01).In every period the FI of MMP-3,10 was higher than control group(P＜0.01),the FI of TIMP-1 was higher than control group at the fourth and the eighth week(P＜0.01),in every treated group the expression was weaker compared with MsPGN group.Following the diease progressing,the expression of MMP-2 mRNA decreased and TIMP-2mRNA increased,but in treated group the level was weaker.The expression of MMP- 10,TIMP-1 mRNA increased(P＜0.01 or＜0.05),but in treated group the expression was weaker compared with MsPGN group.Following the diease progressing,the activity of MMP-2 weakened,but after treated,the 72KD MMP-2 increased and the activity partly recovered.Conclusions:In MsPGN renal tissue,the expressions of MMPs reduced,its activity weakened.The expressions of TIMPs increased or the ratio of MMPs /TIMPs decreased was the reason of glomerular ECM deposition,and even glomerular sclerosis.TGF-β1 could restrain the expressions of MMPs and induce the expressions of TIMPs.Nourishing kidney and activing blood recipe of traditional Chinese medicine could induce the expressions of MMPs and partly recover its activity,restrain the expressions of TIMPs at the same time,decrease the composition of collagen;Nourishing kidney and activing blood recipe of traditional Chinese medicine could resist glomerular sclerosis and postpone the course of chronic renal failure.