Effect Of Fosinopril On Fractalkine Expression And CD68 Positive Cell In Renal Tissue Of Diabetic Rats

Objective: To investigate the effect of fosinopril on CX3C chemokine fractalkine and CD68 positive cell expression and its renoprotective mechanism in renal tissue of diabetic rats.Methods: The rats were randomly divided into four groups, including normal control(NC group), nephrectomized rats(NE group), diabetic rats(DM group) and diabetic rats treated with fosinopril(DF group). Diabetes was induced by injection of streptozotocin after nephrectomy. Immunohistochemistry was used to examine the expression of fractalkine and CD68 positive cells. The mRNA of fractalkine was detected by RT–PCR.Results: After 8 weeks, the level of blood glucose and 24h urine albumine in DM group rats was significantly higher than those of NC and NE group(P<0.05). The area of glomerullar capillaries increased markedly, and the mesangial matrix expanded lightly and diffusely, meanwhile aggravated segmetally. The inflammatory cell infiltration in glomeruli can be observed. The above-metionded changes have improved dramatically in DF group except the blood glucose level(P<0.05). Fractalkine mRNA and protein expression in rat kidney of DM group markedly increased compared with those of NC group and NE group (area density:3.18±0.45; mRNA:0.53±0.11;P<0.05), and CD68 positive cell infiltration in diabetic glomeruli also increased markedly(11.67±0.70/gcs;P<0.05). The increased expression of fractalkine protein and mRNA, as well as CD68 positive cell infiltration was inhibited in DF group(aera density: 0.88±0.29;mRNA:0.23±0.10; 1.11±0.02/gcs; P<0.05). The number of CD68 positive cell in glomeruli is positively correlated with the mRNA expression of fractalkine (r=0.807, P<0.01).Conclusion: Fractalkine up-regulation was demonstrated in diabetic kidney. This up-regulation, as well as CD68 positive cell infiltration was suppressed after 8 weeks treatment with fosinopril. These findings suggested that fractalkine may play an important role in inflammatory progression of diabetic nephropathy. Fosinopril may inhibit macrophage recruitment and regulate the inflammation of diabetic nephropathy by suppressing the expression of fractalkine.