| [Objective]Renal interstitial fibrosis is a common approach of various causes of renal disease progression to end-stage renal failure. Tubulointerstitial inflammatory lesions is to promote renal interstitial fibrosis, one of the main factors, infiltration of monocytes/macrophages not only by secreting cytokines, inflammatory mediators and production of oxygen free radicals, contributing to mesangial cell proliferation and secretion of a large number of inflammatory factors, but also produce extracellular matrix extracellular matrix leading to increased tubular interstitial fibrosis. Intercellular adhesion molecule 1 (ICAM-1) are adhesion molecules of the immunoglobulin superfamily, contribute to mononuclear cells in the organization are moving to strengthen the MCP-1 on monocyte chemotactic effect. Studies have shown that Monocyte chemotactic factor 1 (MCP-1) may be mediated by macrophages involved in renal interstitial fibrosis. To induce inflammatory cells to the renal interstitial tissue infiltration and aggregation of key inflammatory molecules, may exacerbate the tissue damage and delaying the repair organization. Erythropoietin is secreted by the kidneys of endogenous cytokines, previous studies that the EPO is widely used in the treatment of anemia caused by a variety of reasons. In recent years, study found EPO on acute renal injury suggesting a protective mechanism of anti-oxidative stress, anti-apoptosis, anti-inflammatory effect, but the protective effect of chronic renal failure, prevention of renal fibrosis in the domestic no relevant reports. In this paper, rat 5/6 nephrectomy Methods of renal interstitial fibrosis model as an object of study, the renal pathological changes were measured by immunohistochemical ICAM-1, MCP-1 expression and changes, and apply the EPO to intervene in order to further explore the drug to improve the role of renal interstitial fibrosis and its possible mechanism.[Methods]32 male SD rats weighing 150-200g, keeping the environment clean, room temperature 20℃～25℃, the free ingestion of drinking water during the test. Randomly selected 8 to sham-operated group (Sham group, n=8), only the line of the same anesthesia and exposure and dissection renal capsule, will not do nephrectomy and the remaining 24 for 5/6 nephrectomy.10% chloral hydrate anesthetized rats by intraperitoneal injection (300 mg·kg-1), skin preparation, disinfection, left back row next to the middle vertical incision exposed the left kidney, perirenal fat capsule separated after the occlusion of left renal pedicle, the upper and lower pole kidney were removed 1/3, using gelatin sponge hemostasis moment, release the clip arteries were observed after the reset without bleeding kidneys, layer by layer closure of the abdominal cavity,1 week after complete removal of right kidney,2 surgical removal of a total of 5/6 kidney. Two times 1 week after surgery when the surgical group were randomly divided into model group (STNx group, n=8), low-dose EPO treatment group (TA group),8 rats given EPO 30u/kg, intraperitoneal injection 3 times a week; large dose of EPO treatment group (TB group),8 rats given EPO 50u/kg, intraperitoneal injection 3 times a week. Model group and sham-operated group was given warm water gavage were observed for 12 weeks to monitor body weight changes, Urine, blood and tissue samples. Detection of 24h urinary protein, serum creatinine SCr; immunohistochemistry determined ICAM-1, MCP-1 expression and changes; by HE stained kidney pathological observation.[Results]The SPSS 11.0 software for data analysis. Separately for various data analysis of variance, paired t test and correlation analysis.1.24h urine protein, and SCr:Compared with sham-operated group, model group, 24h urine protein, SCr levels increased (P＜0.01); Compared with model group, EPO dose, high dose treatment group can be reduced 24h urine protein, and SCr level, but the role of high-dose group was significantly better than low-dose treatment group (P ＜0.05).2.Comparison of Renal Pathology:(1) sham-operated group:glomerular structure, no obvious abnormalities, tubular arranged in neat rows, was "back to back" shape, tubular lumen without crystals deposition; no abnormal changes in renal interstitial, non-fibrous tissue hyperplasia. (2) model group:glomerular mesangial cell proliferation, mesangial matrix showing focal or diffuse widened, capillary pressure narrows, segmental sclerosis more common; some small tubular atrophy, surrounded by tubular compensatory expansion of part of the renal tubular lumen seen in the protein tube; interstitial fibrous (3) EPO treatment groups:in particular, high-dose group shows mesangial cells and matrix of light to moderate hyperplasia, and atrophy of glomerular capillary collapse rare, occasionally capillaries, focal segmental sclerosis; tubular expansion, epithelial cells, occasionally protein cast deposition; renal interstitial edema.3.1mmunohistochemical indicators of change:sham-operated rats a small amount of tubulointerstitial MCP-1 expression in the model rats tubulointerstitial expression of MCP-1 compared with the sham group was significantly increased (P＜0.01), the treatment group Compared with model group were decreased (P＜0.05), in which a downward trend in high-dose group significantly (P＜0.05), the results suggest that EPO can inhibit rat MCP-1 expression in high-dose group effects are particularly obvious. Sham-operated group the expression of ICAM-1 is very weak, the model group ICAM-1 expression compared with sham-operated group was significantly higher (P＜0.01); the treatment group and model group were decreased (P＜0.05), in which high-dose group decline significantly (P＜0.05), the results suggest that EPO can inhibit rat ICAM-1 expression, high-dose group effects are particularly obvious.[Conclusion]An intercellular adhesion molecule (ICAM-1) and monocyte chemotactic factor (MCP-1) Department of renal interstitial fibrosis induced by inflammatory factors; 2 by erythropoietin (EPO) intervention, reduced intercellular adhesion molecule (ICAM-1) and monocyte chemotactic factor (MCP-1), for delaying the process of renal interstitial fibrosis provide a basis for.3 for the erythropoietin (EPO) in reducing the incidence of chronic kidney disease, development of strong evidence. |
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