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尿液多標(biāo)志物組合檢測(cè)在馬兜鈴酸腎毒性評(píng)價(jià)中的應(yīng)用

發(fā)布時(shí)間:2018-05-31 09:44

  本文選題:馬兜鈴酸 + 中性粒細(xì)胞明膠酶相關(guān)脂質(zhì)運(yùn)載蛋白; 參考:《中國(guó)新藥與臨床雜志》2015年07期


【摘要】:目的探討腎損傷標(biāo)志物中性粒細(xì)胞明膠酶相關(guān)脂質(zhì)運(yùn)載蛋白(NGAL)、腎損傷因子1(KIM-1)和白細(xì)胞介素18(IL-18)在馬兜鈴酸誘導(dǎo)的大鼠腎損傷中的變化特征及其組合檢測(cè)的意義。方法取Wistar大鼠隨機(jī)分為馬兜鈴酸(25 mg·kg-1)組和對(duì)照組(等容量生理鹽水)各12只,隔兩日一次尾靜脈注射給藥,共兩周。于不同時(shí)間點(diǎn)采集血、尿樣,于末次給藥和停藥一周后分批解剖處理。生化分析儀檢測(cè)血清尿素氮(BUN)、肌酐(Cr)含量,酶聯(lián)免疫吸附法(ELISA)檢測(cè)尿液NGAL、KIM-1、IL-18濃度。光鏡下觀察腎臟病理組織形態(tài)學(xué)改變。采用ROC曲線比較各血清或尿液標(biāo)志物及其組合的曲線面積。結(jié)果馬兜鈴酸組大鼠腎小管病理?yè)p傷明顯,停藥后亦未恢復(fù);與對(duì)照組相比,血清BUN、Cr于末次給藥后顯著升高(P0.05),停藥1周后均恢復(fù),尿液NGAL、KIM-1和IL-18于不同時(shí)間點(diǎn)明顯升高(P0.01)。ROC分析顯示其組合檢測(cè)可提高效能,尤其NGAL+KIM-1和NGAL+KIM-1+IL-18組合的曲線下面積分別為0.928和0.927,遠(yuǎn)高于BUN、Cr及其組合BUN+Cr。結(jié)論尿液NGAL、KIM-1和IL-18的組合檢測(cè)更能提高檢驗(yàn)效能,可預(yù)測(cè)或提示馬兜鈴酸誘導(dǎo)的腎小管損傷。
[Abstract]:Objective to investigate the changes of neutrophil gelatinase-associated lipid carrier protein (NGALL), renal injury factor (KIM-1) and interleukin-18 (IL-18) in rat kidney injury induced by aristolochic acid. Methods Wistar rats were randomly divided into two groups: control group (n = 12) and control group (n = 12). Blood and urine samples were collected at different time points. Serum bun (bun) and creatinine (Cr) were determined by biochemical analyzer, and urine NGALL KIM-1 (IL-18) was detected by enzyme linked immunosorbent assay (Elisa). The histopathological changes of kidney were observed under light microscope. The ROC curve was used to compare the area of each serum or urine marker and its combination curve. Results the pathological injury of renal tubules in aristolochic acid group was obvious and did not recover after drug withdrawal, compared with the control group, the serum bun Cr increased significantly after the last administration of aristolochic acid, and all recovered after 1 week of withdrawal. Urine NGALL KIM-1 and IL-18 increased significantly at different time points P0.01U 路ROC analysis showed that the combined detection could improve the efficiency, especially the area under the curve of the combination of NGAL KIM-1 and NGAL KIM-1 IL-18 was 0.928 and 0.927 respectively, which was much higher than that of Buchon Cr and its combination BUN Cr. Conclusion the combined detection of urinary NGALL KIM-1 and IL-18 can improve the efficiency and predict the renal tubule injury induced by aristolochic acid.
【作者單位】: 上海中醫(yī)藥大學(xué)藥物安全評(píng)價(jià)研究中心;
【基金】:國(guó)家“重大新藥創(chuàng)制”科技重大專項(xiàng)項(xiàng)目(2009ZX09502-002) 國(guó)家重點(diǎn)基礎(chǔ)研究發(fā)展計(jì)劃(973計(jì)劃)(2009CB522807) 上海市教委預(yù)算內(nèi)項(xiàng)目(2010JW30)
【分類號(hào)】:R965.3

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本文編號(hào):1959193


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