Experimental Study of Effects of TCM YiShen Decoction Combined with Prednisone and Enalapril on Expressions of MMP-9 and TIMP-1 in Kidney Tissue of Mice with IgA Nephropathy

【Objective】 To explore the contents and mRNA expressions of matrix metalloproteinase-9(MMP-9) and tissue inhibitor of metalloproteinase-1(TIMP-1) in kidney tissue of mice with IgA nephropathy(IgAN) and the effects of TCM YiShen Decoction combined with prednisone and enalapril on them.【Methods】 The IgAN model was established by the method of oral intake of bovine serum albumin(BSA) together with the injection of staphylococcus enterotoxin B(SEB) through caudal vein.The mRNA expressions of MMP-9 and TIMP-1 were measured by fluorescent quantitative polymerase chain reaction(FQ-PCR) and the contents of MMP-9 and TIMP-1 protein were measured by immunohistochemistry.【Results】No significant differences of mRNA and protein expression of MMP-9 and TIMP-1 were found between the low concentration and high concentration Yishen Decoction group.But the secretion and mRNA expression of TIMP-1 in the low and high concentration Yishen Decoction group was decreased than the IgAN model group(PU:14.9 ± 6.1 vs 18.0 ± 7.7,15.6 ± 6.0 vs 18.0 ± 7.7;mRNA:0.665±0.198 vs 0.884 ± 0.247,0.713 ± 0.221 vs 0.883 ± 0.247)(P 0.05),while that of MMP-9 was stronger than the model control group(PU:8.9 ± 3.0 vs 6.9 ± 2.7,8.9 ± 3.3 vs 6.9 ± 2.7;mRNA expression:0.397 ± 0.047 vs 0.297 ± 0.025,0.386 ± 0.027 vs 0.297 ± 0.025;P 0.05).Among the five treatment groups,the prednisone plus enalapril plus Yishen Decoction group showed the weakest mRNA and protein expression of TIMP-1(PU:9.2 ± 3.4;mRNA expression:0.293 ± 0.068) and the strongest expression of MMP-9(PU:34.3 ± 8.7;mRNA expression:1.265 ± 0.433).【Conclusion】The abnormal expression of MMP-9,TIMP-1 mRNA and protein play important roles in the onset and development of IgAN.The TCM Yishen Decoction can reduce the abnormal expression of the mRNA and protein of TIMP-1,strengthen the mRNA and protein expression of MMP-9 so as to slow down the renal injury that was less obvious than the combination of prednisone with enalapril.The combination of prednisone plus enalapril plus Yishen Decoction has better treatment effect than single use of combination of prednisone and enalapril or the single use of Yishen Decoction to modulate the abnormal expression of MMP-9 and TIMP-1 mRNA and protein in kidney tissue of mice with IgA nephropathy.