| Objective: Renal interstitial fibrosis is a common characteristic of chronic renal functional lesion. Compared to glomerular sclerosis,the correlation of the degree of renal interstitial fibrosis and the degree of renal functional lesion is much more closed. So, renal fibrosis is often believed to play a reliable indicator in the progression of chronic renal diseases.There are lots of pathogenesy and factors of renal interstitial fibrosis the degree of macrophage's collecting is related to the level of fibrosis. Macrophage's collecting is the beginning of renal interstitial fibrosis. Because interstitial macrophage comes from histoleucocyte of blood, chemotatic factors of renal interstitium educe important effection. Osteopontin (OPN) is the most important chemokine to aspirate renal interstitial macrophage; its expression is close correlation to interstitial inflammation and fibrosis. OPN not only have the tendency to attract macrophage of circulation to renal interstitial, but also stimulate intrinsic inflammatory cells and start or expand inflammation. Inflammation cans injury renal tubule. Next step is fibroblast activation, renal tubule's extinction.The researches indicate that OPN can stimulate renal tubular epithelial cells (TECs) proliferating and rebuilding. It can also help them recover when they are injured at early stage. But this function loses compensation gradually along with pathology headwaying seriously. So through blocking OPN to anti-aggregation and proliferation of macrophage we can relieve inflammation, decrease renal tubule's lesion and inhibit fibrosis. CD44 is a main ligand of OPN, lots of studies indicated that CD44 educed an import effective in inflammation process.Sodium ferulate(SF)is a compond sodium salt of ferulate, well water solubility, which was proved to be a receptor antagonist of the endothelin. It can remove free radical, prevent lipid over oxidation injury, antagonize vascular contraction, blood pressure elevation and the cell proliferation of vascular smooth muscle induced by endothelin. It can delay renal interstitial fibrosis and protect renal function. The reports that effect of sodium ferulate on the expression of OPN in rat kidney with unilateral ureteral occlusion (UUO) were not found. This study is about renal interstitial fibrosis through UUO. To observe the expression of OPN and CD44 in renal tubular epithelial and the chances of OPN and CD44 after sodium ferulate intervention.We research OPN participates development of renal interstitial fibrosis and try to find the protection of sodium ferulate to renal interstitial fibrosis. Methods: 54 male SD rats were randomly divided into 3 groups: sham-operated group (Group A, n=18), UUO group (Group B, n=18), UUO with Sodium ferulate treated group (GroupC, n=18). Under Chloral Hydrate anesthesia (0.1ml/Kg body wt,i.p), the left ureter was ligated by 4.0 silk at two points and cut between the ligatures in order to prevent retrograde urinary tract infection. Group A had their ureters manipulated but not ligated. Sodium ferulate (110mg/Kg body wt in drinking water) began to administrate one day before surgery. Group A and Group B were received equal volume Saline by daily gastric gavage. Six rats of each group were killed respectively at 3, 7, 14 days after the operations, and their operated kidmey were harvested for HE,Masson staining Immunohistochemistry staining, and we made comparision between three group.Immunohistochemistry was used on renal tissue for osteopontin (OPN), CD44, ED-1, which was a maker of macrophage.Histological change were also observed by HE staining and Masson staining. The results were analyzed semi-quantitatively by the pathological image analysis system. All the data were analysed by SPSS 11.0 statistics software, P value<0.05 was considered to have statistical significance.Results: There were different degrees of interstitial fibrosis, interstitial leukocyte infiltration, tubular dilation and the relative area of renal tubulointerstitium expantion in the obstructed kidneys of groups B3, B7, B14 days after UUO in light microscrope using the staining mathods of HE and Masson. The relative area of renal tubulointerstitium was significantly increased in the obstructed kidneys compared with that of group A (P<0.05). However, the relative area of renal tubulointerstitium of group C significantly decreased compared with that of group B (P<0.05). The results of immunohistochemical staining: OPN chiefly expressed in the renal tubule and renal interstitial. OPN had almost no expression in glomerulus. OPN were lowerly expressed in group A. While the level of OPN in group B was significantly increased than that of group A and it reached the peak at 14 day after operations. In group C, the level of OPN was lower than that of group B at the same timepoint (P<0.05). CD44 expressed in the nucleus of renal tubular epithelial cells. CD44 had a small quantity of expression in group A. After 3d, the expression of CD44 in group B started to upgrade and reached the peak at the fourtheenth day. The expression of CD44 in group C is higher than that of group A (P<0.05). The expression of monocyte was occasionally found in group A and the expression was higher and higher along with the obstructed time. Group C had significant change compared with group B, and the difference had statistical significance (P<0.05). The expression entensity of OPN and CD44 were correlated with the interstitial macrophages accumulation. Conclusion: Elevated OPN expression might be responsible for the macrophages infiltration and interstitial fibrosis in the obstructed kidney. Sodium ferulate can protect renal function and delay the progression of renal interstitial fibrosis. A probably molecule mechanism is decreasing the expression of OPN.
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