The Study Of Chinese Herbal Compound On Adriamycin Nephropathy Tubule Injury Protection Mechanisms

Objectives: To assess the efficacy of Buyi Pishen Formula (BPF) on the adriamycin induced nephropathy (AIN) rats, to investigate the different expression of MMP-9 and TIMP-1 in each group and explore the mechanism of defending renal tubule, to analyze the effective dose of BPF.Methods: The AIN rats model was induced by adriamycin. According to the result of excretion of Urine protein in 24 hours, the rats were randomly sent to control group ,benazepril group,low dose of traditional Chinese medicine(LD T.C.M.)group, moderate dose of traditional Chinese medicine (MD T,C,M.)group, and high dose of traditional Chinese medicine(HD T.C.M) group.The blank groupwas only injected with isotonic Na chloride. After the 28 days' treatment,we observed the general status of rats, detected excretion of Urine protein, urea nitrogen and serum creatinine. All the animals were sacrificed at the end of the experiment. And we detected TGF-β1, MMP-9, TIMP-1 with immunohistochemistry, observed the difference of every group by electron microscope.Results: Firstiy, the excretion of Urine protein (EUP) was detected on the 7^th day and the peak appeared on the 14^th day; Secondly, in both benazepril and T.C.M groups, the excretion of Urine protein is lower than that in the control group. And the HD T.C.M group is rather significant than that of the others groups (p<0.01). Thirdly, on the immunohistochemiscal observation, the up-regulation of MMP-9 and the down-regulation of TIMP-1 in the control group are significant than that of the blank group, which had been studied on the 48^th day (p<0.01). The MMP-9 has been down-regulated and the TIMP-1 correspondingly up-regulated in the HD T.C.M. group(p<0.01); while in the LD T.C.M group and M.D T.C.M group, the MMP-9 has been up-regulated and the TIMP-1 has been down-regulated, even compared with the control group (p<0.01). The conspicuous differences were not found between in the benazepril group and in the control group. On the regulation of TGF-β1, not only in the benazepril group but in each T.C.M group also, the TGF-β1 has been down-regulated, especially in the H.D T.C.M group (p<0.01). Both the glomerulus and tubule injuries were found by the observation of electron microscope.Conclusions: BPF can alleviate the EUP in AIN; On the regulation of MMP-9 and TIMP-1, BPF has double effects; The efficacy of BPF for advanced AIN tubular injury is dose -related.