骨形成蛋白4对单侧输尿管梗阻小鼠肾间质巨噬细胞聚集及核因子-κB信号通路的影响

Effect of bone morphogenetic protein 4 on the infiltration of macrophages and the expression of nuclear factor-κB in mice model of unilateral ureteral obstruction

目的 探讨骨形成蛋白4（bone morphogenetic proteins,BMP4）对单侧输尿管梗阻（uni-lateral ureteral obstruction,UUO）小鼠肾间质巨噬细胞聚集及核因子-κB信号通路的影响.方法 将雄性C57BL/6小鼠随机分为腹腔注射生理盐水假手术组（n=8）、腹腔注射生理盐水UUO组（n=8）、腹腔注射anti-BMP4假手术组（n=8）、腹腔注射anti-BMP4 UUO组（n=8）.各组于手术日起每天给予anti-BMP4[200 μl/（g·体重）]或生理盐水腹腔注射.于术后7 d处死取材.免疫组织化学观察肾组织巨噬细胞标记物CD68、p-P65表达;Western印迹检测肾组织p-P65蛋白表达.结果 免疫组织化学显示,anti-BMP4-假手术组和生理盐水假手术组CD68、p-P65表达差异无统计学意义（P均〉0.05）;与生理盐水UUO组比较,anti-BMP4 UUO组CD68、p-P65表达均明显降低（P均〈0.05）.同样,Western印迹显示,anti-BMP4-假手术组和生理盐水假手术组p-P65蛋白表达差异无统计学意义（P〉0.05）;与生理盐水UUO组比较,anti-BMP4 UUO组p-P65蛋白明显降低（P〈0.05）.结论 BMP4参与梗阻性肾病肾间质炎症过程,这一过程可能通过激活核因子-κB信号通路起作用.

Objective To observe the effect of bone morphogenetic protein 4（BMP4） on the infil-tration of macrophages and the expression of nuclear factor-κB in mice model of unilateral ureteral obstruc-tion（UUO）.Methods C57BL/6 mice were randomly divided into four groups：injected intra-abdominally with saline-sham-operated group（saline-sham group,n =8）,injection intra-abdominally with saline-UUO-operated group（saline-UUO group,n=8）,injection intra-abdominally with anti-BMP4-sham-operated group （anti-BMP4-sham group,n=8）,and injection intra-abdominally with anti-BMP4-UUO-operated group（anti-BMP4-UUO group,n=8）.Either saline or anti-BMP4（group 200 μl/gram of body weight per day） were injected intra-abdominally for 7 days after surgery.Mice were sacrificed at 7th day to evaluate the expression of CD68 and p-P65 by immunohistochemical staining in each group.Besides,the p-P65 protein level was also analyzed by Western blotting in four groups.Results Immunohistochemical staining showed that the expres-sions of CD68 and p-P65 were significantly reduced in the kidney cortices in anti-BMP4-UUO group than in saline-UUO group（P〈0.05,respectively）.Similar to that,the p-P65 protein level was significantly reduced in the kidney cortices in anti-BMP4-UUO group than in saline-UUO group（P 〈 0.05,respectively）. Conclusion BMP4 participates in the process of renal interstitial inflammation in obstructive nephropathy, and may play a role through the activation of nuclear factor-κB signaling pathway.