鈣化性納米微粒致腎結石大鼠尿液中性粒細胞明膠酶相關脂質運載蛋白、骨橋蛋白及單核細胞趨化蛋白-1的變化及其意義
本文選題:腎結石 + 鈣化性納米微粒; 參考:《中國現代醫(yī)學雜志》2015年23期
【摘要】:目的在建立鈣化性納米微粒(CNPs)致大鼠腎結石模型的過程中,檢測大鼠不同時間尿液中的中性粒細胞明膠酶相關脂質運載蛋白(NGAL)、骨橋蛋白(OPN)、單核細胞趨化蛋白-1(MCP-1)的含量,初步分析CNPs致腎結石的形成機制。方法利用腎結石患者術中所得結石培養(yǎng)出CNPs,制成CNPs混懸液。20只SD雄性大鼠隨機分為CNPs誘石組(A組)和空白對照組(B組)。通過鼠尾靜脈注射CNPs感染大鼠,分別于注射后4 h、12 h、24 h、1周、2周及8周用代謝籠收集大鼠尿液,酶聯免疫分析法(ELISA)檢測大鼠各時間尿液中NGAL、OPN、MCP-1的含量。于注射CNPs后1、2和8周分批次處死大鼠,腎臟組織HE染色后于光鏡下觀察其結晶的形成及病理改變,對照分析結晶的形成與大鼠尿液中NGAL、OPN、MCP-1含量變化的關系。結果在注射CNPs后4 h,與B組比較,A組的NGAL水平顯著增高(P0.05),2周時A組的OPN、MCP-1水平開始大幅度升高(P0.05),8周時A組的NGAL、OPN、MCP-1的含量均明顯升高(P0.05)。1周時,A組腎臟組織可見少量腎小管上皮細胞顆粒樣變性,腎小管內未見鈣鹽晶體沉積;2周時,A組腎小管內可見少量鈣鹽晶體沉積,伴有少數腎小管上皮細胞空泡樣變性和顆粒樣變性;2周后腎小管內鈣鹽晶體的沉積量與NGAL、OPN、MCP-1的含量呈正相關;8周時,A組腎小管內可見大量鈣鹽晶體沉積,伴有廣泛腎小管上皮細胞空泡樣變性,腎小管上皮細胞的病理改變程度與NGAL的含量呈正相關;B組腎臟組織未見鈣鹽沉積和病理改變。結論大鼠感染CNPs 4 h后即腎小管上皮細胞開始受到損傷,并且損傷程度與NGAL水平呈正相關。2周后腎小管內開始出現鈣鹽晶體的黏附和聚集,單核-巨噬細胞和OPN參與其黏附和聚集過程,并且鈣鹽晶體的沉積量隨損傷程度加重也相應增加。
[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.
【作者單位】: 瀘州醫(yī)學院附屬醫(yī)院泌尿外科;
【基金】:四川省科技廳資助項目(No:14JC0105) 四川省衛(wèi)生廳資助項目(No:100288)
【分類號】:R692.4
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