钙化性纳米微粒致肾结石大鼠尿液中性粒细胞明胶酶相关脂质运载蛋白、骨桥蛋白及单核细胞趋化蛋白-1的变化及其意义

发布时间：2018-06-28 17:13

本文选题：肾结石 + 钙化性纳米微粒　；参考：《中国现代医学杂志》2015年23期

【摘要】：目的在建立钙化性纳米微粒(CNPs)致大鼠肾结石模型的过程中,检测大鼠不同时间尿液中的中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、骨桥蛋白(OPN)、单核细胞趋化蛋白-1(MCP-1)的含量,初步分析CNPs致肾结石的形成机制。方法利用肾结石患者术中所得结石培养出CNPs,制成CNPs混悬液。20只SD雄性大鼠随机分为CNPs诱石组(A组)和空白对照组(B组)。通过鼠尾静脉注射CNPs感染大鼠,分别于注射后4 h、12 h、24 h、1周、2周及8周用代谢笼收集大鼠尿液,酶联免疫分析法(ELISA)检测大鼠各时间尿液中NGAL、OPN、MCP-1的含量。于注射CNPs后1、2和8周分批次处死大鼠,肾脏组织HE染色后于光镜下观察其结晶的形成及病理改变,对照分析结晶的形成与大鼠尿液中NGAL、OPN、MCP-1含量变化的关系。结果在注射CNPs后4 h,与B组比较,A组的NGAL水平显著增高(P0.05),2周时A组的OPN、MCP-1水平开始大幅度升高(P0.05),8周时A组的NGAL、OPN、MCP-1的含量均明显升高(P0.05)。1周时,A组肾脏组织可见少量肾小管上皮细胞颗粒样变性,肾小管内未见钙盐晶体沉积;2周时,A组肾小管内可见少量钙盐晶体沉积,伴有少数肾小管上皮细胞空泡样变性和颗粒样变性;2周后肾小管内钙盐晶体的沉积量与NGAL、OPN、MCP-1的含量呈正相关;8周时,A组肾小管内可见大量钙盐晶体沉积,伴有广泛肾小管上皮细胞空泡样变性,肾小管上皮细胞的病理改变程度与NGAL的含量呈正相关;B组肾脏组织未见钙盐沉积和病理改变。结论大鼠感染CNPs 4 h后即肾小管上皮细胞开始受到损伤,并且损伤程度与NGAL水平呈正相关。2周后肾小管内开始出现钙盐晶体的黏附和聚集,单核-巨噬细胞和OPN参与其黏附和聚集过程,并且钙盐晶体的沉积量随损伤程度加重也相应增加。
[Abstract]:Objective to investigate the levels of neutrophil gelatinase-associated lipid carrier protein (NGAL), osteopontin (OPN) and monocyte chemoattractant protein-1 (MCP-1) in urine of rats induced by calcified nanoparticles (CNPs). To analyze the formation mechanism of CNPs induced renal calculi. Methods CNPswere cultured from calculi of patients with renal calculi. CNPs suspension. 20 male SD rats were randomly divided into CNPs induced stone group (group A) and blank control group (group B). Rats infected with CNPs were injected with CNPs via tail vein. The urine of rats was collected by metabolic cage at 4 h, 12 h, 24 h, 1 week, 2 weeks and 8 weeks after injection. The levels of NGALP OPN MCP-1 in urine of rats were detected by enzyme linked immunosorbent assay (Elisa). The rats were killed at 2 and 8 weeks after injection of CNPs. The formation of crystallization and pathological changes were observed under light microscope after HE staining. The relationship between the formation of crystallization and the content of NGALOOPNMCP-1 in urine of rats was analyzed. Results at 4 hours after CNPs injection, the level of NGAL in group A was significantly higher than that in group B (P0.05). At 2 weeks after injection, the level of OPNMP-1 in group A began to increase significantly (P0.05). At 8 weeks after injection, the level of NGALOOPNMCP-1 in group A was significantly higher than that in group B (P0.05). A small amount of renal tissue was found in group A at week 1. 1. Granular degeneration of epithelial cells, In group A, a small amount of calcium crystals could be found in the tubules at 2 weeks after no calcium crystal deposition was found in the tubules. There was a positive correlation between the amount of calcium crystals deposited in renal tubules and the content of MCP-1 in NGALL OPN at 8 weeks after vacuolar degeneration and granuloid degeneration of a few renal tubule epithelial cells. A large amount of calcium crystal deposition could be seen in the tubules of group A at 8 weeks. The degree of pathological changes of renal tubular epithelial cells was positively correlated with the content of NGAL. There was no calcium deposition and pathological changes in renal tissues in group B. Conclusion the renal tubular epithelial cells begin to be damaged 4 h after CNPs infection in rats, and the degree of injury is positively correlated with NGAL level. 2 weeks later, the adhesion and aggregation of calcium crystals begin to appear in the renal tubules. Mononuclear macrophages and OPN participate in the process of adhesion and aggregation, and the deposition of calcium crystals increases with the severity of damage.
【作者单位】：泸州医学院附属医院泌尿外科;
【基金】：四川省科技厅资助项目(No:14JC0105) 四川省卫生厅资助项目(No:100288)
【分类号】：R692.4

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