| Objective: Renal interstitial fibrosis is a common consequence of progressive renal diseases. As renal fibrotic changes well correlate with the reduction of glomerular filtration rate in the chronic renal diseases, renal fibrosis is believed to play a crucial role in the progression of chronic renal diseases.Renal tubulointerstitial injury is characterized by inflammatory cell infiltrate: however, the stimuli for leukocyte recritment are not fully understood. Macrophage has the decisive significance.The degree of macrophage's collecting is related to the level of fibrosis.Macrophage's collecting is the beginning of renal interstitial fibrosis. 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 can 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.Telmisartan is a new recipient antagonist of angiotensin II .It can depress blood pressure, decrease proteinuria and protect renal function. The reports that effect of micardis 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. We research the protection of telmisartan to renal interstitial fibrosis and macrophage's infiltrate and try to find the mechanism of anti-fibrosis, postpone the progression of renal diseases.Methods:72 male SD rats were randomly divided into 3 groups : sham-operated group(Group A,n=24), UUO group(Group B,n=24), UUO with Micardis (telmisartan) treated group(Group C,n=24).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. Micardis (27mg/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 1,4,7,14 days after the operations. At the fourteenth day,the samples of blood and the urine of 24 hours were collected to detected the concentration of serum creatinine,the quantity of urinary protein and creatinine. Immunohistochemistry was used on renal tissue for osteopontin (OPN) , proliferating cell nuclear antigen (PCNA) , ED-1, which was a maker of macrophage.Histological change were also observed by HE staining. The results were analyzed semi-quantitatively by the pathological image analysis system. All the data were analysed by SAS 6.12 statistics software, P value<0.05 was considered to have statistical significance.Results: There were no significant difference of the quantity of urinary protein of 24 hours and the clearance rate of creatinine of rats among all of groups(P > 0.05). 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 B1, B4, B7, B14 days after operations in light microscrope using the staining mathods of HE.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 4 day after operations.In group C, the level of OPN was lower than that of group B at the same timepoint(P<0.05).PCNA expressed in the nucleus of renal tubular epithelial cells. PCNA had a small quantity of expression in group A.The expression of PCNA in group B reached the peak at 4 day and then declined at the fourtheenth day.The expression of PCNA 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 no significant change compared with group B, but the difference had no statistical significance(P>0.05). The expression entensity of OPN was correlated with the interstitial macrophages accumulation (r = 0.9852, 0.9037, 0.9298, 0.9859, P<0.05) .Conclusion: Elevated OPN expression might be responsible for the macrophages infiltration and interstitial fibrosis in the obstructed kidney. Telmisartan can protect renal function and delay the progression of renal interstitial fibrosis. Decreasing the expression of OPN and increasing the expression of PCNA probably are the probabe mechanism. Telmisartan has no effect on the filtration of monocyte. The roles may have the relation of OPN.
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