| Objective: Renal interstitial fibrosis represents the common Pathway for various renal diseases to develop chronically to end-stage renal failure. Tubulointerstitial inflammation and fibrosis are the major pathophsiological events in renal progressive damage. They are closely correlated with renal injury, which decide kidney function. So, It is important to prevent tubulointerstitial fibrosis. At current, It is believed that the formation of tubulointerstitial fibrosis involves many clues, such as acumulation of inflammtory cells, damage, activation, proliferation and phenotypic change of primate renal interstitial cells, be-fibrosis cytokins autocrine and extracellular matrix components unbalance in accumulation and degradation, Which results in a mass of extracellular matrix components accumulating in kidney. These causes renal units losing, glomerular filter rate descending progressively. At last, the renal function failure is mediated. With the development for cell mollecule technology, It has currently been improved that platelet-derived growth factor (PDGF) and its receptor participate in forming glomerulosclerosis, and they play animportant role in glomerular damage, It is not known in our nation whether they have effect on tubulointerstitial fibrosis. therefore, from the experimentaPangle, We investigated the expressing condition of PDGF and its receptor in tubulointerstitial cells following UUO, and a -SMA expression, CD68 positive cell too. So far, Irbesartan has been used in controling Hypertension, reducing protenial urine and diabetic nephropathy. Whether it has protective effect on tubulointerstitial fibrosis is not known. So, Irbesartan was used in tubulointerstitial fibrosis model in rats. The protective effect of Irbesartan on tubulointerstitial fibrosis in rats and its possible mechanism were investigated. The theoretic basement was advanced for preventing and curing interstitial fibrosis.Methods: Helthy Femal Sprague-Dawley rats, Weighting 180g to 220g, were used in this experiment. All animals underwent surgical procedures, 24 rats underwent unilateral uretal obstruction: under pentobarbital anesthesia (5.0mg/kg body wt, i.p), the left ureter was ligated with 4.0 silk at two points and cut between the ligatures in order to prevent retrograde uninary tract infection, these rats were randomly divided into 2 groups: UUO group and treatement group (Irb group), the other 12 rats served as control group (sham group), whose ureters were manipulated but not ligated. The UUO group and sham group received tap water beginning 24 hours before surgery, while the Irb treatmentgroup were fed on Irbesartan (60mg/kg body wt in drinking water) beginning 24 hours before surgery, all rats were allowed free access to food and*water. 7 days and also 14 days after the treatment with tap water or lrbesartan, the following studies were performed in every group. All of the items such as serum creatinine, the amount of 24 hours urine, urine protein, and Urine beta2-microglobulin were measured. The expression of PDGF-B,PDGFR- P , a -SMA and CD68 positive cell number were estimated by immunohistochenical technique, and the results were analyzed semi-quantatively with the pathological image analysis system. The renal tissue of all rats was observed with light microscope after HE and periodic acid-schiff (PAS) staining and transmission electron microscope, the results of interstitial relative area were also analyzed semi-quantitatively with the pathological image analysis system. The experimental data was demonstrated in mean± standard deviation. The analysis of variance and q test were used to the significance test and SPSS 10.0 measured the relation about the data with linear correlation and significance t test.Results: During the animal experiment, the serum creatinine was measured in sham group, UUO group and Irb group at 7 days, while it was higher in UUO group and Irb group than that in sham group at 14 days(p<0.05), it was lower in Irb group than that in UUO group at 14 days also(p<0.05). The level of urine protein and P 2-MG was compared between three groups and there was significant difference at the same period. it*was higher in UUO group and Irb group than that in sham group(p<0.05). and lower in Irb group than that in UUO(p<0.05). The semi-quantitative results of interstitial relative area and expression of PDGF-B, PDGFR- P , a -SMA and CD68 positive cell in three groups were compared together at the same period, the results showed that there was a significant difference in three groups: positive area of PDGF-B, PDGFR- P , a -SMA and CD68 positive cell number were increasingly more strong in interstitial in UUO group and Irb group than that in sham group(p<0.05), and also,it was reduced significantly in Irb group than that in UUO group(p<0.05),except CD68.The renal interstitial expression of PDGF-B,PDGFR- P were significantly associated with the relative area of interstitial and a -SMA expression(r=0^ 0.92; 0.91 > 0.81, (p<0.05) , The renal interstitial expression of PDGF-B was significantly associated with CD68 positive cell number in interstitial (r=0.95,0.95,p<0.05) .while the expression of PDGFR- P in renal interstitial was not associated with CD68 positive cell number in interstitial (r=0.64,0.49,p > 0.05) .The pathological chang in UUO group showed that there was a mass of inflammatory interstitial infiltration,epithelium degeneration,loss and interstitial expassion at 7 days,which...
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