肾损伤分子1对顺铂诱导的大鼠急性肾损伤的预测研究

目的 对肾损伤分子1 (KIM-1)预测顺铂诱导的大鼠急性肾损伤进行研究.方法 以顺铂为工具药,诱导大鼠急性肾损伤模型.采集尿样、肾组织样本,对肾组织样本进行病理切片检查,以确定造模是否成功.用ELISA法测定尿样中KIM-1蛋白含量;RT-PCR法检测大鼠肾脏KIM-1基因表达水平;Western blotting法检测大鼠肾组织中KIM-1的蛋白含量,并通过免疫组化法定性定位分析大鼠肾组织中KIM-1蛋白表达情况,以确定急性肾损伤发生时KIM-1是否可以作为敏感的检测指标.结果 当模型组大鼠肾脏皮髓交界处出现程度不等的肾小管扩张,肾小管上皮细胞变性、坏死脱落,基底膜裸露等病理改变时,ELISA法检测尿KIM-1,RT-PCR法和Western blotting法检测肾组织中的KIM-1表达水平均明显升高,免疫组化显示模型组所有大鼠在肾皮髓交界部位可见大量的染色阳性的肾小管,该染色阳性区域与组织病理学检查中的异常肾小管分布区域基本一致.结论 KIM-1可作为一种敏感的生物标志物对顺铂诱导的大鼠急性肾损伤进行预测.     

化学药物诱导的大鼠急性肾损伤模型中肾损伤分子-1表达的研究

目的：观察肾损伤分子-1(kidney injury molecule-1,Kim-l)在由顺铂、庆大霉素、环孢素诱导大鼠急性肾损伤(acute kidneyinjury,AKI)模型肾组织内的变化,探讨其与AKI之间的相关性。 方法：建立庆大霉素、顺铂、环孢素诱导大鼠AKI模型,运用实时荧光定量PCR法检测肾Kim-1基因表达水平,Western blot法检测肾脏Kim-1蛋白表达水平,分析肾Kim-1表达水平与急性肾损伤的相关性。结果：病理学检查发现顺铂、庆大和环孢素对大鼠肾脏造成不同程度的肾小管损伤,所建AKI模型成功。各模型组与对应对照组比较,肾Kim-l mRNA水平均高于阴性对照组,差异具有统计学意义（P 均＜0.05）;肾Kim-l蛋白在各阴性对照组内呈阴性结果,而在顺铂、庆大和环孢素AKI模型组内均呈阳性表达。结论：化学药物诱导AKI发生时,肾Kim-1基因转录和蛋白表达水平与肾损伤直接相关,为以尿Kim-1作为预测早期肾损伤的生物标志物提供可靠依据。     

肾损伤分子-1、丛生蛋白和胱抑素C对庆大霉素诱导的大鼠肾损伤早期预测的研究

目的应用庆大霉素(GM)诱导的大鼠亚急性肾损伤模型,研究一组新的生物标志物肾损伤分子-1(kidneyinjury molecule-1,Kim-1)、丛生蛋白(clusterin)和胱抑素C(cystatinC)在尿液中的变化,并与传统生物标志物血肌酐(SCr)和尿素氮(BUN)进行比较,评价其对肾损伤的早期预测性。方法建立GM诱导的大鼠亚急性肾损伤动物模型,检测不同给药时间点模型组和对照组大鼠的SCr、BUN和尿Kim-1、clusterin与cystatinC水平,并进行肾组织病理学检查。结果在SCr、BUN和肾组织病理学未出现异常变化时,大鼠尿Kim-1、clusterin、cystatinC就表现出明显的升高,并随给药时间延长呈线性升高。在SCr、BUN和尿Kim-1、clusterin和cystatinC测定结果的ROC曲线中,尿Kim-1、clusterin和cystatinC的曲线下面积均大于0.9。结论尿Kim-1、clusterin和cystatinC在肾损伤中具有良好的敏感性和特异性,能够提高对药物诱导的肾损伤的早期预测能力。     

尿肾损伤分子-1对药物肾毒性诊断性能的研究

目的 在庆大霉素诱导大鼠急性肾损伤模型中评价尿肾损伤分子-1(Kim-1)作为肾毒性生物标志物的诊断性能。方法 ip 60和120 mg/kg庆大霉素,每天给药1次,连续10 d,制备大鼠急性肾损伤模型。在给药第2、4、8、11天,进行肾脏组织病理分析,检测尿液Kim-1、血清尿素氮(BUN)和肌酐(Cr)水平。结果 病理学结果显示,庆大霉素组大鼠出现典型肾损伤变化,呈明显的剂量及时间相关性;与对照组比较,庆大霉素低、高剂量组尿液Kim-1浓度在给药第4天即开始出现显著升高(P<0.05),增幅程度明显高于传统指标BUN和Cr,并且呈显著剂量和时间相关性;受试者操作特性曲线(ROC)结果表明,尿Kim-1的曲线下面积(AUC)明显优于BUN和Cr。结论 尿Kim-1的肾毒性诊断性能优于传统肾功能评价指标,可作为一种药物肾毒性的候选生物标志物。     

白细胞介素-32在大鼠急性肾损伤后的表达及意义

目的:探讨白细胞介素(IL)-32在缺血所致大鼠急性肾损伤后的表达及意义。方法:将40只雄性SD大鼠随机分为对照组和急性肾损伤组(AKI组),每组20只,采用夹闭双侧肾蒂的方法制备缺血性急性肾损伤大鼠模型。自动生化分析仪测定血肌酐(SCr)、血尿素氮(BUN)水平,酶联免疫吸附试验检测大鼠血清IL-32、尿液中肾损伤分子(KIM)-1的表达。结果:术后5、7d,AKI组的SCr水平均较对照组显著升高(P0.05);术后3、5、7d,AKI组血清IL-32、尿KIM-1水平均较对照组显著升高(P0.05);术后7d,AKI组血清IL-32、尿KIM-1水平与肾小管损伤评分正相关;AKI组术后BUN水平在术后有一过性升高。结论:IL-32在大鼠急性肾损伤后高表达,且水平与肾损伤程度正相关,可作为AKI早期诊断的生物学标志物。     

抑制NF-κB信号通路对顺铂致肺癌大鼠肾损伤的保护作用及其分子机制研究

摘要：目的:探索抑制核转录因子（NF）-κB信号通路对顺铂致肺癌大鼠肾损伤的保护作用及其分子机制研究。方法:将50只大鼠随机分为5组:正常对照组、肺癌组（Lewis细胞）、顺铂组(Lewis细胞+腹腔注射顺铂溶液5 mg·kg-1)、吡咯烷二硫代氨基甲酸盐（PDTC）组(Lewis细胞+腹腔注射PDTC 25 mg·kg-1)、PDTC+顺铂组（Lewis细胞+腹腔注射顺铂和PDTC）,每组10只。末次给药后,生化分析仪检测血清肌酐（SCr）、尿素氮（BUN）、胱抑素C（Cys C）、尿液肾损伤分子-1（Kim-1）水平,ELISA法测定肾组织中超氧化物歧化酶（SOD）和丙二醛（MDA）水平,RT-PCR检测肾组织肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-6水平,Western Blotting检测核因子2相关因子2（Nrf2）、血红素氧合酶-1（HO-1）、NF-κB p65、p-IκBα/IκBα的表达,HE染色检测肾组织损伤。结果:与肺癌组相比,顺铂组大鼠血SCr、BUN、Cys C、尿Kim-1水平及肾组织MDA、TNF-α、IL-1β、IL-6 mRNA、Nrf2、HO-1、NF-κB p65和p-IκBα/IκBα的表达明显升高（P<0.05）,肾组织SOD活性和GSH-Px活性明显降低（P<0.05）;与顺铂组相比,PDTC+顺铂组大鼠血SCr、BUN、Cys C、尿Kim-1水平及肾组织MDA、TNF-α、IL-1β、IL-6 mRNA、NF-κB p65和p-IκBα/IκBα的表达明显明显降低（P<0.05）,肾组织SOD、GSH-Px、Nrf2和HO-1的表达明显升高（P<0.05）。结论:抑制NF-κB信号通路可以降低炎症因子水平,还可以激活Nrf2的表达,降低氧化应激水平,保护顺铂致肺癌大鼠的肾组织损伤。     

内源性物质3-硫酸吲哚酚用于肾损伤早期诊断的探讨

目的研究内源性物质3-硫酸吲哚酚用于肾损伤早期诊断的意义。方法以抗癌药顺铂、甲氨蝶呤为研究对象,取雄性Sprague-Dawley大鼠36只,随机分为3组,分别为顺铂组、甲氨蝶呤组和空白组。于给药后第1、3和5天采集血清与新鲜肾组织。采用LC-MS法测定各组大鼠血清中3-硫酸吲哚酚的质量浓度;同时分析各组大鼠血清中生化指标肌酐和尿素氮浓度以及肾脏组织病理学变化。结果单次给药后,肾组织病理学结果显示顺铂组与甲氨蝶呤组大鼠在第3天均可见明显肾损伤;各组中内源性物质3-硫酸吲哚酚于第3天明显升高;顺铂组肌酐与尿素氮于第5天明显升高,甲氨蝶呤组肌酐与尿素氮无明显变化。结论在顺铂和甲氨蝶呤致肾损伤模型中,内源性物质3-硫酸吲哚酚显示了较常规生化指标血肌酐与尿素氮更高的灵敏度。     

尿液新型生物标志物对顺铂诱导大鼠急性肾早期损伤的诊断效能研究

目的 在顺铂诱导的大鼠急性肾损伤模型中,系统评价短时间采尿下系列尿液肾毒性生物标志的诊断性能。方法 Wistar大鼠单次ip 6 mg·kg^-1顺铂构建急性肾损伤模型,在检疫期、给药后第3和6天分别收集给药后5 h对照组和顺铂组动物尿液和血样,使用日立7180全自动生化仪测定血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)、尿素氮(BUN)、肌酐(CRE)以及尿液样本中尿葡萄糖苷酶(NAG)、尿总蛋白(uTP)、尿肌酐(uCr)水平;使用Luminex仪器测定尿液中丛生蛋白(CLU)、谷胱甘肽S转移酶-α(GST-α)、干扰素诱导蛋白-10(IP-10)、肾损伤因子-1(KIM-1)、骨桥蛋白(OPN)、组织金属蛋白酶抑制剂-1(TIMP-1)、血管内皮生长因子-A(VEGF-A)、酸性糖蛋白(AGP)、白蛋白(Alb)、β₂微球蛋白(β₂M)、半胱氨酸蛋白酶抑制剂C(CysC)、表皮生长因子(EGF)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平。结合动物肾脏组织病理学检查,制作受试者操作特性曲线(ROC)进行肾毒性标志物的灵敏度和特异性分析。结果 顺铂组动物AST、ALT、TBIL值与各自对照组比较无统计学差异,且解剖大体检查并未发现除肾脏以外其他组织器官病变,排除其他组织器官病变对肾生物标志物变化的影响。组织病理学结果证实顺铂诱导动物模型均出现典型急性肾损伤:外髓质外带肾小管上皮细胞变性/坏死和髓质蛋白管型等。与对照组比较,传统标志物血清BUN和CRE在顺铂给药第6天、动物严重肾损伤时才出现显著升高(P<0.05);而IP-10、KIM-1、Alb、β2M和CLU生物标志物则在给药第3天已出现显著增加(P<0.05),且持续升高,增幅明显高于传统指标。ROC分析结果表明,IP-10、CysC、KIM-1和Alb的曲线下面积(AUC)明显优于BUN和CRE,具有更高的灵敏度和特异性。结论 尿液IP-10、CysC、KIM-1和Alb的肾毒性诊断性能优于传统生物标志物BUN和CRE,建议可作为药物致急性肾毒性早期诊断的生物标志物。     

鼠尾草酸对庆大霉素诱导急性肾损伤的保护作用

目的研究鼠尾草酸对庆大霉素(GM)诱导急性肾损伤的作用及其可能的机制。方法将SD大鼠随机分为对照组、模型组、阳性对照组以及鼠尾草酸低、中、高剂量组。鼠尾草酸给药组和阳性对照组分别用不同剂量的鼠尾草酸或肾衰宁灌胃7 d,同时合并GM腹腔给药,模型组单独使用GM处理7 d。检测血清中肌酐(SCr)和血尿素氮(BUN)的水平;HE染色检测肾脏组织的病理改变情况;免疫组化检测各组大鼠肾脏组织中肾损伤分子-1(KIM-1)的表达;检测各组大鼠肾组织中丙二醛(MDA)和过氧化氢(H_2O_2)的含量,诱导型一氧化氮合酶(iNOS)和超氧化物歧化酶(SOD)的酶活力;酶联免疫吸附测定法检测肾脏组织中单核细胞趋化蛋白1(MCP-1)和肿瘤坏死因子α(TNF-α)的含量;Western Blot法测定肾脏组织中p66shc和p-p66shc的蛋白表达。结果与对照组比较,模型组大鼠血清SCr和BUN水平上升,MDA、H_2O_2含量和iNOS酶活力明显上升,SOD酶活力下降;与模型组比较,鼠尾草酸中、高剂量组可降低这些改变。与对照组相比,肾脏组织中MCP-1、TNF-α、KIM-1以及p-p66shc含量明显上升;与模型组比较,鼠尾草酸中、高剂量可降低GM诱导肾脏组织中MCP-1、TNF-α、KIM-1以及p-p66shc的含量。结论鼠尾草酸能显著降低GM诱导的急性肾损伤,其机制与抑制p66shc介导的氧化应激有关。     

原花青素通过SIRT1/AMPK信号通路对庆大霉素致大鼠急性肾损伤的改善机制

目的 探究原花青素对庆大霉素致大鼠急性肾损伤（AKI）的改善机制。方法 通过腹腔注射硫酸庆大霉素构建AKI大鼠模型,将造模成功的大鼠随机分为模型对照组、盐酸贝那普利5 mg/kg组（阳性对照）、原花青素50 mg/kg组、原花青素100 mg/kg组、原花青素200 mg/kg组,每组10只;另取10只正常大鼠作为正常对照组。各给药组大鼠灌胃相应药液,正常对照组和模型对照组大鼠灌胃等体积生理盐水。所有大鼠每天给药1次,连续28 d。末次给药后,检测血清中血清肌酐（SCr）、尿素氮（BUN）、丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）及24 h尿液中尿蛋白（UP）水平;计算肾脏指数;观察大鼠肾组织病理变化并进行病理评分;检测肾组织细胞凋亡率和胱天蛋白酶-3(Caspase-3)、B细胞淋巴瘤2基因相关X蛋白（Bax）表达水平,以及沉默信息调节因子1(SIRT1)、AMP活化蛋白激酶（AMPK）蛋白的磷酸化水平。结果 与模型对照组比较,各给药组大鼠SCr、BUN、UP、MDA水平,肾脏指数,肾组织病理评分,肾组织细胞凋亡率及肾组织中Caspase-3、B...     

Age-related differences in kidney injury biomarkers induced by cisplatin

Acute kidney injury (AKI) occurs in a half of cisplatin (CDDP)-treated patients. Traditional biomarkers including blood urea nitrogen (BUN) and serum creatinine (SCr) are still used for detection of CDDP-induced AKI, but these biomarkers are not specific or sensitive. The aim of this study was to identify the specific and sensitive biomarkers against CDDP-induced renal injury between young (3-week-old) and old (20-week-old) rats. All animals were intraperitoneally injected once with CDDP (6 mg/kg). After 3 days, all animals were sacrificed and serum, urine, and kidney tissues were collected. Urinary and serum biomarkers as well as histological changes were measured. CDDP-induced proximal tubular damage was apparent from histopathological examination, being more severe in 3-week-old rats accompanied by increased number of TUNEL-positive apoptotic cells. This was associated with elevated urinary kidney injury molecule-1 (KIM-1), glutathione-S-transferase alpha (GST-α), vascular endothelial growth factor (VEGF), and tissue inhibitor of metalloproteinases-1 (TIMP-1). In contrast, the levels of neutrophil gelatinase-associated lipocalin (NGAL) and osteopontin were significantly increased in 20-week-old rats after CDDP treatment. These results indicate that the use of age-specific urinary biomarkers is necessary to diagnosis of CDDP-induced AKI. Especially, urinary KIM-1, GST-α, TIMP-1, and VEGF levels may help in the early diagnosis of young patients with CDDP-induced AKI.     

Identification of a sensitive urinary biomarker,selenium-binding protein 1, for early detection of acute kidney injury

Acute kidney injury (AKI) is associated with increased mortality rate in patients but clinically available biomarkers for disease detection are currently not available. Recently, a new biomarker, selenium-binding protein 1 (SBP1), was identified for detection of nephrotoxicity using proteomic analysis. The aim of this study was to assess the sensitivity of urinary SBP1 levels as an early detection of AKI using animal models such as cisplatin or ischemia/reperfusion (I/R). Sprague–Dawley rats were injected with cisplatin (6 mg/kg, once i.p.) and sacrificed at 1, 3, or 5 days after treatment. Ischemia was achieved by bilaterally occluding both kidneys with a microvascular clamp for 45 min and verified visually by a change in tissue color. After post-reperfusion, urine samples were collected at 9, 24, and 48 hr intervals. Urinary excretion of protein-based biomarkers was measured by Western blot analysis. In cisplatin-treated rats, mild histopathologic alterations were noted at day 1 which became severe at day 3. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at day 3. Levels of urinary excretion of SBP1, neutrophil gelatinase-associated lipocalin (NGAL), and a tissue inhibitor of metalloproteinase-1 (TIMP-1) were markedly elevated at day 3 and 5 following drug treatment. In the vehicle-treated I/R group, serum levels of BUN and SCr and AST activity were significantly increased compared to sham. Urinary excretion of SBP1 and NGAL rose markedly following I/R. The urinary levels of SBP1, NGAL, TIMP-1, and KIM-1 proteins excreted by AKI patients and normal subjects were compared. Among these proteins, a marked rise in SBP1 was observed in urine of patients with AKI compared to normal subjects. Based upon receiver-operator curves (ROC), SBP1 displayed a higher area under the curve (AUC) scores than levels of SCr, BUN, total protein, and glucose. In particular, SBP1 protein was readily detected in small amounts of urine without purification. Data thus indicate that urinary excretion of SBP1 may be useful as a reliable biomarker for early diagnosis of AKI in patients.     

乌司他丁对脓毒症致急性肾损伤大鼠肾脏病理及尿相关指标的影响

目的探讨乌司他丁对盲肠结扎穿孔术（CLP）所致大鼠脓毒症急性肾损伤肾脏病理及尿相关指标的影响。方法 SD健康雄性大鼠55只,按随机化原则分成3组：正常对照组5只、模型组25只、乌司他丁治疗组25只,后两组再随机分为5个时间点（1、6、12、24、48 h）,每组每时间点各5只,采用CLP复制脓毒症模型,乌司他丁治疗组造模后立即给予乌司他丁100 000 U/kg,尾静脉注射,分别在各个时间点采血、留尿标本,处死大鼠摘取肾脏,进行肾功能血肌酐（SCr）、尿素氮（BUN）,尿肾损伤分子（KIM-1）、白细胞介素-18（IL-18）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）检测分析,光镜下观察肾脏病理变化。结果模型组SCr、BUN的浓度CLP术后6 h开始升高,24 h达高峰,48 h开始下降,均显著高于对照组（P〈0.05）,乌司他丁治疗组12、24、48 h均显著低于相应时间点模型组（P〈0.05）。模型组尿KIM-1、NGAL、IL-18含量于CLP术后1 h开始升高,12 h达高峰,24 h开始下降,均显著高于对照组,乌司他丁治疗组6、12、24、48 h均显著低于相应时间点模型组（P〈0.05）。肾脏病理改变明显好于模型组。结论乌司他丁对脓毒症所致急性肾损伤具有肾脏保护作用。     

肾静脉上结扎大鼠下腔静脉及合并右肾切除后的肾功能改变和川芎嗪对其的影响

目的　探讨肾静脉平面以上结扎大鼠下腔静脉、合并右肾切除及应用川芎嗪后的肾功能及肾脏病理改变。方法　分别在肾静脉平面以上结扎大鼠下腔静脉、肾静脉平面以上结扎下腔静脉并右肾切除、肾静脉平面以上结扎下腔静脉并川芎嗪治疗 ,术后第 6、12、2 4小时 ,2、3、4、5、7天检测血肌酐、尿素氮、2 4h尿量及N 乙酰 D 氨基葡萄糖酶 (NAG)并观察肾脏病理改变。结果　肾静脉平面以上结扎大鼠下腔静脉后血肌酐、尿素氮、尿NAG升高 ,肾脏淤血并见大量管型。术后第 3天 ,肾脏恢复正常结构 ;术后第 4天 ,血肌酐、尿素氮恢复正常 ;术后第 5天 ,尿ANG恢复正常。肾静脉平面以上结扎下腔静脉并右肾切除术后第 5天 ,血肌酐、尿素氮、尿NAG恢复正常 ,肾脏淤血较重 ,部分动物 2 4h内死亡。肾静脉平面以上结扎下腔静脉并川芎嗪治疗术后第 4天 ,血肌酐、尿素氮、尿NAG酶恢复正常 ,肾脏淤血较轻。结论　肾静脉平面以上结扎大鼠下腔静脉可因双肾淤血而影响肾功能 ,但术后第 5天即可完全代偿。若在肾静脉平面以上结扎下腔静脉并右肾切除 ,不但增加手术难度和风险 ,还能进一步损害肾功能 ,增加术后 2 4h动物死亡率。若在肾静脉平面以上结扎下腔静脉附加川芎嗪治疗 ,可明显改善肾功能。建议当遇病人患有腹膜后肿瘤侵及肾静脉?     

奥美拉唑调控肾脏转运体OCT2和P-gp保护顺铂诱导的急性肾损伤

目的：基于肾脏有机阳离子转运体OCT2、多药耐药相关蛋白P-糖蛋白（P-gp）研究奥美拉唑（OME）在大鼠及肾小管上皮细胞中拮抗顺铂诱导急性肾损伤的作用机制。方法：选择雄性SD大鼠随机分为空白组、模型组、药物组（1.8 mg·kg^-1和3.6 mg·kg^-1）以及OME对照组。OME对照组和药物组连续5 d腹腔注射OME,药物组在第5 d腹腔注射顺铂（15 mg·kg^-1）,模型组连续注射5 d生理盐水,第5天腹腔注射顺铂;空白组以上述相同时间注射生理盐水。各组在第7天取血和肾脏,通过HE染色和生化指标BUN、Cr检测观察肾组织损伤程度;MTT法检测肾小管上皮HK-2细胞存活率,Western blot检测OCT2和P-gp蛋白表达。结果：（1）OME能够减轻顺铂对HK-2细胞的损伤程度,提高细胞生存率;（2）与模型组比较,OME降低大鼠死亡率和肾脏肥大指数,改善肾小管空泡变性和炎性浸润,明显降低血清生化指标BUN和Cr水平;（3）Western blot实验结果表明在HK-2细胞和SD大鼠中,OME能够抑制肾脏OCT2的表达,上调外排转运体P-gp的表达。结论：OME能够在大鼠和细胞中有效保护顺铂诱导的急性肾损伤,其保护机制与OME抑制OCT2的表达,上调P-gp的表达有关。     

补肾化浊胶囊对庆大霉素诱发大鼠急性肾损害作用的实验观察

目的 探讨补肾化浊胶囊对庆大霉素（GM）致大鼠肾脏损伤时肾功能变化以及血、尿中相关指标的影响.方法 给药21d后,采用大剂量注射GM致大鼠急性肾损伤模型,同时给予补肾化浊胶囊高、低剂量混悬液灌胃.治疗7 d,观察4组血肌酐（Cr）,尿素氮（BUN、总蛋白（TP）和白蛋白（ALB）的变化;另观察4组尿蛋白、葡萄糖、酮体的变化及肾组织的病理改变.结果 补肾化浊胶囊高、低剂量组血清中Cr、BUN、TP和ALB含量较模型组同指标比较差异有统计学意义（P〈0.05）;尿中尿蛋白、葡萄糖、酮体含量较模型组同指标比较差异有统计学意义（P〈0.05）.补肾化浊胶囊高、低剂量组的相同指标与对照组比较差异无统计学意义（P〉0.05）.结论 补肾化浊胶囊对GM诱发大鼠急性肾损伤有显著保护作用.     

Comparison of kidney injury molecule-1 and other nephrotoxicity biomarkers in urine and kidney following acute exposure to gentamicin, mercury, and chromium.

Sensitive biomarkers are needed to detect kidney injury at the earliest stages. The objective of this study was to determine whether the appearance of kidney injury molecule-1 (Kim-1) protein ectodomain in urine and kidney injury molecule-1/hepatitis A viral cellular receptor-1 (Kim-1/Havcr1) gene expression in kidney tissue may be more predictive of renal injury after exposure to nephrotoxicants when compared to traditionally used biomarkers. Male Sprague-Dawley rats were injected with a range of doses of gentamicin, mercury (Hg; HgCl2), or chromium (Cr; K2Cr2O7). The results showed that increases in urinary Kim-1 and kidney Kim-1/Havcr1 gene expression paralleled the degree of severity of renal histopathology and were detected at lower doses of nephrotoxicants when compared to blood urea nitrogen (BUN), serum creatinine, and urinary N-acetyl-beta-D-glucosaminidase (NAG). In a time course study, urinary Kim-1 was elevated within 24 h after exposure to gentamicin (100 mg/kg), Hg (0.25 mg/kg), or Cr (5 mg/kg) and remained elevated through 72 h. NAG responses were nephrotoxicant dependent with elevations occurring early (gentamicin), late (Cr), or no change (Hg). At 72 h, after treatment with any of the three nephrotoxicants, there was increased Kim-1 immunoreactivity and necrosis involving approximately 50% of the proximal tubules; however, only urinary Kim-1 was significantly increased, while BUN, serum creatinine, and NAG were not different from controls. In rats treated with the hepatotoxicant galactosamine (1.1 mg/kg), serum alanine aminotransferase was increased, but no increase in urinary Kim-1 was observed. Urinary Kim-1 and kidney Kim-1/Havcr1 expression appear to be sensitive and tissue-specific biomarkers that will improve detection of early acute kidney injury following exposure to nephrotoxic chemicals and drugs.     

体外循环及非体外循环冠状动脉搭桥术对心肌和肾脏损伤的影响

目的比较体外循环及非体外循环冠状动脉搭桥术术后早期对心肌和肾脏损伤程度的影响。方法 66例冠状动脉搭桥术患者随机均分为体外循环(A)组和非体外循环(B)组,比较两组术后24h内心肌肌钙蛋白Ⅰ(cTnⅠ)、肌酸磷酸激酶MB(CK-MB)水平和血尿素氮(BUN)、血清肌酐(SCr)、血清胱蛋白酶抑制剂C(Cys C)水平、尿N-乙酰-β-氨基葡萄糖苷酶(NAG)活性、内生肌酐清除率。结果术后24h内,A组cTnⅠ、CK-MB水平及BUN、血清Cr水平、尿NAG活性均比B组明显升高(P<0.05)。结论非体外循环冠状动脉搭桥术术后早期心肌及肾脏损伤程度较体外循环者轻。