福辛普利对糖尿病大鼠肾组织中Fractalkine及CD68阳性细胞表达的影响

Effect of Fosinopril on the Expression of Fractalkine and CD68 Positive Cells in Diabetic Kidney Tissue in Rats

目的探讨福辛普利对糖尿病大鼠肾组织中CX3C类趋化因子Fractalkine和CD68(巨噬细胞标记物)阳性细胞表达的影响及其肾脏保护作用的机制。方法采用免疫组织化学法及RT-PCR检测肾组织中Fractalkine表达,同时采用免疫组织化学法检测肾组织CD68阳性细胞的分布,并对结果进行半定量分析。结果治疗8周后,免疫组织化学法及RT-PCR检测DM组大鼠肾组织中Fractalkine表达增强(P<0.05),肾小球内CD68阳性细胞显著增多,DF组Fractalkine表达明显减弱(P<0.05),同时肾小球内CD68阳性细胞亦显著减少,相关分析显示肾小球CD68阳性细胞数与Fractalkine mRNA表达呈正相关。结论Fractalkine在糖尿病肾组织中表达明显增强,且与肾小球内CD68阳性细胞表达正相关,说明该趋化因子在糖尿病性肾病炎症反应中起重要作用;治疗组大鼠Fractalkine较模型组明显降低,表明福辛普利对肾脏的保护作用可能与下调fractalkine,抑制糖尿病炎症状态有关。

Objective To investigate the effect of fosinopril on the expression of CX3C chemokine fractalkine and CD68 positive cells and its reno-protective 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, fractalkine mRNA and protein expression in rat kidney of DM group were markedly increased as compared with that of NC group and NE group （P 〈 0. 05 ）. The increased expression was suppressed by the treatment with fosinopril. Increased infiltration of CD68 positive cells in diabetic glomeruli was also inhibited by the treatment （P 〈 0. 05 ）. The number of CD68 positive cells in glomeruli was positively correlated with the mRNA expression of fractalkine （ r = 0. 807, P 〈 0. 01 ）. Conclusion Fractalkine up-regulation was demonstrated in diabetic kidney. The up-regulation, as well as CD68 positive cell infiltration, was suppressed by the treatment with fosinopril for 8 weeks. These findings suggest that fractalkine expression may play an important role in the inflammatory progression of diabetic nephropathy. Fosinopril may inhibit inflammation of diabetic nephropathy by suppressing the expression of fractalkine.