Abstract:

Abstract:Objective To observe the influence of tacrolimus in the expressions of matrix metalloproteinase-9(MMP-9)  and  tissue inhibitor of metalloproteinase-1(TIMP-1) in kidney tissue of   the  rats  with IgA nephropathy (IgAN),　and to explore the treatment effect of tacrolimus on glomerular fibrosis  and its mechnism,and to provide basis for IgAN treatment.Methods 40 healthy male SD Wistar were selected to set up experimental IgAN rat models  with bovine serum albumin (BSA)+ lipopolysaccharide(LPS)+ carbon tetrachloride (CCl4).The IgAN model rats were  randomly divided into  model group (n=8),tacrolimus group (n=8),benazepril group (n=8),benazepril+ tacrolimus group (n=8);at the same time  normal control  group was  established(n=10).The rats in  model group,tacrolimus group,benazepril group,benazepril+tacrolimus group,and control group were given distilled water,tacrolimus,benzepril,benazepril+tarcolimus and distilled water,respectively;the levels of MMP-9,TIMP-1,and MMP-9/TIMP-1 in kidney  tissue of the rats in various groups were detected.Results Compared with normal group,the kidney tissue of the rats in benazepril +tacrolium group,tacrolium group,benazepril group and  model group showed claybank  dyeing area and the expressions  of MMP-9 and TIMP-1 in   kidney tissue of the rats in model group were strong positive;the expressions  of MMP-9 and TIMP-1 in   kidney tissue of  the rats in benazepril+tacrolimus group,tacrolimus group,and benazepril group  were  positive.The ratio of MMP-9/TIMP-1 in kidney tissue of the  rats in normal control group was closed to 1;the ratio of MMP-9/TIMP-1 in kidney tissue of the  rats in model group was the highest;the ratio of MMP-9/TIMP-1 in kidney tissue of the rats in benazepril+tacrolimus group,and  tacrolimus group,benazepril group were lower than that in  model group(P<0.05);the ratio of  MMP-9/TIMP-1 in benazepril+tacrolimus group was statistically higher  than that  in tacrolimus  group and benazepril group(P<0.05);the ratio of MMP-9/TIMP-1 in tacrolimus group  was statistically higher than that in  benazepril group (P<0.05).Conclusion Tacrolimus can decrease the levels of MMP-9 and TIMP-1  in  kidney tissue  of the rats and  correct the imbalance of MMP-9 / TIMP-1;tacrolium has therapeutic effect on glomerular fibrosis.

Key words: IgA nephropathy, tacrolimus, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1