| The development of renal interstitial fibrosis (RIF) was related to end stage failure. The progressive decline of chronic renal diseases was a highly complex, multi-factorial process, which was poorly understood. The structural features of progressive decline, however, showed comnnon histological features, despite the diverse nature of the primary injury. The development of progressive tubular atrophy and interstitial fibrosis represents a final common pathway leading to renal insufficiency. Four recurrent themes are emerging from studies: (1) Fibrosis was due to a combination of both increased matrix-protein synthesis and inhibition of matrix degradation. Over expression of protease inhibitors, including the tissue inhibitors of metalloproteinases (TIMP) or plasminogen activator inhibitors(PAI) , was the most consistent change in the matrix-degradation pathway. (2) Expression of the fibrogenic cytokine transforming growth factor beta-1 (TGF-1) was up-regulated. (3) The interstitium was infiltrated by cells of the monocyte/macrophage lineage. These cells appear to be an important source of TGF- 1. (4) Although several potential mediators had been investigated , the fundamental mechanisms involved in the recruitment of circulating monocytes into the interstitium remain unknown.Some studies suggested that accumulation and infiltration of the monocyte/macrophage lineage into glomerular and interstitial regions of the kidney was a key event in the pathogenesis of the development of RIF and renal function failure. For the chronically obstructed kidney, cytokines and growth factors released by damaged tubular cells and invading leukocytesmight play a role in the development and progression of fibrotic changes of the renal interstitium. Adhesion molecule upregulation might provide an important pathway in inflammatory reactions, whereby migrating leukocytes and monocyte/macrophage, following extravasation, encounter and adhere to interstitial fibroblast via ICAM-1 or VCAM-1. With respect to the binding of mononuclear cells to firoblast monolayer, the interaction of ICAM-1 with LFA-1 was more significant than the contribution of VCAM-l/VLA-4.Chronic obstructive uropathy was created by maintained unilateral ureter ligation in rats lasting up to 30 days. The progressively severe renal lesion in this model was characterized by marked tubular atrophy, which appeared to be mediated by apoptosis of tubular epithelial cells , expansion of interstitial volume, interstitial inflammation and firosis. Infiltrating inflammatony cells might contribute to tubular injury and activize interstitial fibroblasts, crucial processes leading to the tubular atrophy and interstitial fibrosis characteristic of advanced stages of this lesion. The soybean isoflavone genistein, an inhibitor of tyrosine kinase, was one kind of important non-nutrition component . It had action in preventing tumor genesis, anti-cell proliferation and anti-aging.Some studies showed, the soybean genistein could attenuate inflammation and oxidation. In low dose, genistein could inhibit proliferation of the capillary expithelial cells, and in high dose, genistein could prevente the activity and migration of monocyte/macrophage lineage, it also could block ICAM-1 and VCAM-1.In our study , we had created a model of chronic obstructive uropathy by maintained unilateral ureter ligation in rats(UUO) lasting up to 30 days. By the mean time , we breed UUO rats with soybean genistein, and then examination of renal sections were taken after 5 days till 30 days. (1) The results of morphological and biochemical characterization of fibrosis showed clear signsof RIF in the fibrosis control group than in the genistein therapy group. Genistein significantly inhibited the volume of renal interstitium increased. (2) By electron microscope, there were lots of the proliferating renal cortical fibroblasts in the fibrosis group, and few of the parenchymal cells. But in the genistein therapy group ,we could see some tubular cells proliferating active, and the number...
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