本文選題：順鉑 + 急性腎損傷　； 參考：《廣西醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：通過檢測尿視黃醇結(jié)合蛋白（RBP）及中性粒細(xì)胞明膠酶相關(guān)脂質(zhì)轉(zhuǎn)運蛋白（NGAL）在順鉑致大鼠急性腎損傷（AKI）尿液中的變化，探討尿RBP、NGAL是否為順鉑致大鼠急性腎損傷早期敏感標(biāo)志物，以便早期發(fā)現(xiàn)、早期診治順鉑急性腎損傷。 方法：選取健康雄性SD大鼠48只，隨機(jī)分為順鉑試驗組（CP組）42只，生理鹽水對照組（NS組）6只，CP組按注藥后時間點不同，依次分為CP3h、CP6h、CP12h、CP24h、CP48h、CP72h、CP96h組，各組6只，分別檢測注藥后各個時間點大鼠血肌酐（Scr）、尿素氮（BUN），尿RBP、NGAL等相關(guān)生化指標(biāo),并進(jìn)行統(tǒng)計學(xué)分析，同時觀察各個時間點大鼠腎臟病理變化。 結(jié)果：血生化結(jié)果：CP組SD大鼠腹腔注射順鉑24h內(nèi)，Scr未見明顯變化，24h-48h內(nèi)開始升高，48h時明顯升高，高于NS對照組，差異有統(tǒng)計學(xué)意義（P0.05），72h時Scr明顯較基線升高50%；CP組中的BUN各時間點變化趨勢與Scr各時間點變化趨勢基本一致。 尿生化結(jié)果：CP組中的尿NGAL6h內(nèi)未見明顯異常，6h-12h內(nèi)開始升高，12h時明顯升高，高于NS對照組，差異有統(tǒng)計學(xué)意義（P0.05），24h-72h內(nèi)繼續(xù)升高達(dá)到一個峰值；統(tǒng)計分析顯示尿NGAL與Scr無相關(guān)關(guān)系（P0.05）。CP組中的尿RBP3h內(nèi)未見明顯異常，3h-6h內(nèi)開始升高，，6h時明顯升高，高于NS對照組，差異有統(tǒng)計學(xué)意義（P0.05），6h-96h內(nèi)呈持續(xù)上升趨勢；統(tǒng)計分析顯示尿RBP與Scr呈正相關(guān)（P0.05）。 病理結(jié)果：NS組大鼠腎組織HE染色可見：腎組織結(jié)構(gòu)清晰未見明顯異常，腎小球、腎小管結(jié)構(gòu)正常，間質(zhì)較少；CP組大鼠腎組織HE染色可見：除有淤積紅細(xì)胞外腎小球未見明顯異常，但腎小管明顯變性，可見腎小管上皮細(xì)胞刷狀緣脫落、胞質(zhì)空泡變性、管腔擴(kuò)張、腎小管堵塞、間質(zhì)炎癥細(xì)胞浸潤，甚至出現(xiàn)聚集凋亡細(xì)胞，且腎小管病變隨時間逐漸加重。 結(jié)論：1、在順鉑致大鼠急性腎損傷中,尿RBP、NGAL異常升高明顯早于Scr升高，尿RBP和NGAL一樣是順鉑致大鼠急性腎損傷早期敏感標(biāo)志物；2、尿RBP水平變化還可以反映大鼠順鉑急性腎損傷時腎臟損傷程度；3、腎小管為大鼠順鉑急性腎損傷的主要靶位。
[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.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R692.5

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