Monocyte Chemoattractant Protein-1, Macrophages In Rat Kidney With Unilateral Ureteral Obstruction And The Therapeutic Effect Of Fluvastatin

Objective : l.To investigate the expression of monocyte chemoattractant protein-1 (MCP-1) and macrophages infiltration in renal interstitium and evaluate their pathogenic roles in tubulo-interstitial lesions in rat with unilateral ureteral obstruction; 2.To evaluate the effect of 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor Fluvastatin on MCP-1 expression and macrophages infiltration and further clarify the underlying mechanism of the treatment.Methods: Sixty femal Sprague-Dawley rats underwent UUO and then received vehichle(n=30) or fluvastatin (20mg/kg/d by daily gastric gavage ,n=30) during the 14 days following surgery. Additional thirty rats were sham operated. Six rats of each group were killed respectively at 1,4,7,10,14 days after UUO. Immunohistochemistry was used on renal tissue for monocyte chemoattractant protein-1 (MCP-1), ED-1,which was a marker of macrophage. Histological change were also observed by HE and Masson stain.Result: Immunohistochemical staining of ED-1 positive cells showed a marked increase in macrophages infiltrate in kidney following UUO when compared to sham-operated groups at very time point. The expression of MCP-1 also increased following UUO. ED-1 positive cellsand MCP-1 were correlated with interstitial fibrosis. Fluvastatin reduced MCP-1 production and inhibited interstitial macrophages infiltrate significantly. Additionally, fluvastatin also improved the histological changes of UUO rats.Conclusion: 1.Interstitial macrophages infiltrate play a role in the progression of renal interstitial fibrosis. 2. Elevated MCP-1 expression might be responsible for the macrophages infiltrate and interstitial fibrosis in the obstructed kidney.2. Reduction of MCP-1 in tubules and interstitial macrophage infiltration may be an important event by which fluvastatin prevents renal injury following UUO.