巨噬细胞在高草酸尿症大鼠肾内结石晶体形成过程中的作用

A primary study on the mechanisms of calculus crystal transport by macrophage in rat＇s kidney

目的探讨巨噬细胞转运肾结石晶体形成Randall斑的机制。方法雄性SD鼠25只，随机分为5组，每组5只。A组为对照组，B～E组分别以含1％乙二醇和1％氯化铵的单蒸水加标准颗粒饲料喂养3、5、7、14d建立高草酸尿症大鼠模型。收集各组大鼠24h尿液，离子色谱法测定尿液草酸浓度。免疫组化法检测大鼠肾骨桥蛋白和巨噬细胞的表达，结果以吸光度（A）值表示。透射电镜观察肾小管上皮细胞基底膜和间质处的巨噬细胞和结石晶体。结果A～E5组大鼠尿液草酸浓度分别为（0．22±0．13）、（0．29±0．08）、（0．50±0．26）、（0．41±0．22）、（0．25±0．12）ng／ml；肾髓袢处骨桥蛋白的表达量分别为0．16±0．04、0．25±0．09、0．37±0．10、0．23±0．08、0．19±0．02，骨桥蛋白表达量与尿草酸浓度呈正相关（r＝0．887，P〈0．05）。肾小管上皮细胞基底膜处巨噬细胞表达量分别为0．12±0．08、0．19±0．06、0．27±0．04、0．16±0．03、0．18±0．03，与骨桥蛋白表达量呈正相关（r＝0．596，P〈0．05）。透射电镜下见巨噬细胞趋化至肾髓袢基底膜处，并裂解释放结石晶体。结论巨噬细胞能在。肾骨桥蛋白的趋化作用下将结石晶体转运至髓袢基底膜处，从而成为Randall斑的起源。

Objective To investigate the mechanisms of calculus crystal transport by macrophage in kidney. Methods Hyperoxaluria rat model was established by administration of 1 % ethylene glycol and 1 % ammonium chloridein drinking water. 24 h rat urine was collected, urinary oxalate were analyzed by ion chromatography. The expression and location of osteopontin and macrophage in kidney were observed by immunohistochemistry. Macrophage and calculus crystal at the basement membrane of renal tubular epithelial cells and interstitium were observed. Results The urinary oxalate concentration were （0.22±0.13） ,（0.29±0.08） ,（0.50±0.26）, （0.41 ±0.22）, （0.25±0. 12） ng/ml among these 5 groups. The osteoponitin expression was 0. 16±0.04, 0. 25±0.09, 0. 37± 0.10, 0.23±0.08, 0.19 ±0.02 respectively. The expression of osteopontin was positively correlated with urinary oxlate concentration （r = 0.887, P〈 0.05）. The macrophage at the basement membrane of renal tubular epithelial cells was 0.12±0.08, 0.19±0.06, 0.27±0.04, 0.16±0. 03, 0. 18±0.03 respectively. The macrophage distribution was positively correlated with the expression of osteopontin （r=0. 596,P〈0.05）. The macrophage moved from vessel to the basement membrane of loops of Henle, then disrupted and released the calculus crystal. Conclusions The macrophage might take part in the calculus crystal transport in kidney at the basement membrane of loops of Henle, which may be the source of Randall plaque. This process may be mediated by osteopontin.