尿RBP、NGAL在顺铂致大鼠急性肾损伤中的变化及意义研究

发布时间：2018-05-30 07:56

本文选题：顺铂 + 急性肾损伤　；参考：《广西医科大学》2014年硕士论文

【摘要】：目的：通过检测尿视黄醇结合蛋白（RBP）及中性粒细胞明胶酶相关脂质转运蛋白（NGAL）在顺铂致大鼠急性肾损伤（AKI）尿液中的变化，探讨尿RBP、NGAL是否为顺铂致大鼠急性肾损伤早期敏感标志物，以便早期发现、早期诊治顺铂急性肾损伤。方法：选取健康雄性SD大鼠48只，随机分为顺铂试验组（CP组）42只，生理盐水对照组（NS组）6只，CP组按注药后时间点不同，依次分为CP3h、CP6h、CP12h、CP24h、CP48h、CP72h、CP96h组，各组6只，分别检测注药后各个时间点大鼠血肌酐（Scr）、尿素氮（BUN），尿RBP、NGAL等相关生化指标,并进行统计学分析，同时观察各个时间点大鼠肾脏病理变化。结果：血生化结果：CP组SD大鼠腹腔注射顺铂24h内，Scr未见明显变化，24h-48h内开始升高，48h时明显升高，高于NS对照组，差异有统计学意义（P0.05），72h时Scr明显较基线升高50%；CP组中的BUN各时间点变化趋势与Scr各时间点变化趋势基本一致。尿生化结果：CP组中的尿NGAL6h内未见明显异常，6h-12h内开始升高，12h时明显升高，高于NS对照组，差异有统计学意义（P0.05），24h-72h内继续升高达到一个峰值；统计分析显示尿NGAL与Scr无相关关系（P0.05）。CP组中的尿RBP3h内未见明显异常，3h-6h内开始升高，，6h时明显升高，高于NS对照组，差异有统计学意义（P0.05），6h-96h内呈持续上升趋势；统计分析显示尿RBP与Scr呈正相关（P0.05）。病理结果：NS组大鼠肾组织HE染色可见：肾组织结构清晰未见明显异常，肾小球、肾小管结构正常，间质较少；CP组大鼠肾组织HE染色可见：除有淤积红细胞外肾小球未见明显异常，但肾小管明显变性，可见肾小管上皮细胞刷状缘脱落、胞质空泡变性、管腔扩张、肾小管堵塞、间质炎症细胞浸润，甚至出现聚集凋亡细胞，且肾小管病变随时间逐渐加重。结论：1、在顺铂致大鼠急性肾损伤中,尿RBP、NGAL异常升高明显早于Scr升高，尿RBP和NGAL一样是顺铂致大鼠急性肾损伤早期敏感标志物；2、尿RBP水平变化还可以反映大鼠顺铂急性肾损伤时肾脏损伤程度；3、肾小管为大鼠顺铂急性肾损伤的主要靶位。
[Abstract]:Objective: to detect the changes of urinary retinol binding protein (RBP) and neutrophil gelatinase-associated lipid transporter (NGALs) in the urine of acute renal injury induced by cisplatin in rats. To investigate whether urinary RBP- NGAL is an early sensitive marker of acute renal injury induced by cisplatin in rats, so as to detect and diagnose early acute renal injury caused by cisplatin. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into Cisplatin group (n = 42), NS group (n = 6) and CP group (n = 6). Serum creatinine (SCR), urea nitrogen bun (BUNA) and urinary RBPNNGAL were measured at different time points after injection, and the renal pathological changes of rats were observed at different time points. Results: the blood biochemical results showed that there was no significant change in SCR of SD rats in 24 h after intraperitoneal injection of cisplatin, which was significantly higher than that in NS group. The difference was statistically significant at 72 h after P0.05, Scr was significantly higher than that in baseline. The trend of changes of BUN at each time point in group 50 and CP was basically consistent with that of Scr at each time point. The urine biochemical results showed that there was no obvious abnormality in urinary NGAL6h in the control group (P 0.05), which was higher than that in the NS control group at 12 h after 6 h and 12 h. The difference was statistically significant (P 0.05) and reached a peak value within 24 h. Statistical analysis showed that there was no correlation between urinary NGAL and Scr in the urine RBP3h group. There was no obvious increase of urinary RBP3h in the group of P0.05U. CP within 6 h, which was significantly higher than that in the NS control group. The difference was statistically significant (P 0.05) and showed a continuous upward trend within 6 h. Statistical analysis showed that there was a positive correlation between RBP and Scr in urine (P 0.05). The pathological results showed that there was no obvious abnormality in renal structure, glomeruli and tubules were normal. The HE staining in renal tissue of rats with less interstitial protein showed that there was no obvious abnormality in glomeruli except for the accumulation of red blood cells, but the renal tubules were obviously denatured, the brush edge of renal tubule epithelial cells fell off, the cytosolic vacuoles degenerated, the lumen dilated, the renal tubules were blocked, and the renal tubules were blocked. Interstitial inflammatory cells infiltrated and even apoptotic cells appeared, and the renal tubule lesion gradually aggravated over time. Conclusion in the acute renal injury induced by cisplatin, the abnormal rise of urinary RBP-NGAL was significantly earlier than that of Scr. Urinary RBP and NGAL are the early sensitive markers of acute renal injury induced by cisplatin in rats. The changes of urinary RBP level can also reflect the degree of renal injury in rats with acute renal injury. Renal tubules are the main targets of acute renal injury of cisplatin in rats.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R692.5

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