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      标题:顺铂致大鼠急性肾损伤肾组织病理与血、尿中性粒细胞明胶酶相关脂质运载蛋白的相关性
      作者:孟晓燕,王英,黄雯静,阳延松,舒婷婷,莫薇薇,杨浩强    (广西医科大学第四附属医院肾内科,广西 柳州 545005)
      卷次: 2018年29卷10期
      【摘要】 目的 研究顺铂(DDP)致大鼠急性肾损伤(AKI)动物模型中血、尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)及肾组织细胞凋亡的变化及其相关性。方法 以36只健康雄性Wistar大鼠为研究对象,依随机数表法分为六组,每组各 6只,分别为盐水对照组(CN组)、顺铂 12 h组(CP 12 h组)、顺铂 24 h组(CP 24 h组)、顺铂 48 h组(CP 48 h组)、顺铂96 h组(CP 96 h组)和顺铂144 h组(CP 144 h组)。观察各组大鼠肾组织病理的变化,血、尿NGAL和肾组织细胞凋亡情况,应用Spearman相关分析其相关性。结果 与CN组相比,CP 12 h组及24 h组大鼠肾脏病理出现肾小管上皮细胞空泡变性,部分刷状缘脱落;CP 144 h组大鼠肾脏病理损伤进一步加重,可见肾小管上皮细胞扁平,刷状缘脱落,管腔扩张;CP 12 h组大鼠肾组织凋亡细胞为(1.5±2.1)个/HP,48 h组凋亡细胞显著增加,凋亡细胞为(68.1±11.0)个/HP,明显高于CN组的(0.67±0.82)个/HP,差异均有统计学意义(P<0.05);CP 12 h组大鼠尿NGAL为(2.5±0.5) ng/mL,与CN组的(1.8±0.4) ng/mL相比显著升高,差异有统计学意义(P<0.05);CP 24 h组大鼠的血NGAL为(38.5±10.1) ng/mL,与CN组的(17.2±5.2) ng/mL相比显著升高,差异有统计学意义(P<0.05);CP 48 h组大鼠血、尿NGAL分别为(65.1±6.0) ng/mL、(6.2±1.2) ng/mL,较CN组的血、尿NGAL显著升高,差异有统计学意义(P<0.05);Spearman相关分析显示,肾组织细胞凋亡与血NGAL (r=0.655,P<0.01)、尿NGAL (r=0.657,P<0.01)表达显著相关。结论 DDP致大鼠AKI的早期阶段肾损伤的主要形式表现为细胞凋亡,而血、尿NGAL变化与肾组织细胞凋亡显著相关。
      【关键词】 顺铂;急性肾损伤;中性粒细胞明胶酶相关脂质运载蛋白;发病机制;凋亡;坏死
      【中图分类号】 R-332 【文献标识码】 A 【文章编号】 1003—6350(2018)10—1341—03
Relationship between pathological damage of kidney tissue and serum or urinary neutrophil gelatinase-associatedlipocalin in the rodent model of cisplatin induced acute kidney injury. MENG Xiao-yan, WANG Ying, HUANGWen-jing, YANG Yan-song, SHU Ting-ting, MO Wei-wei, YANG Hao-qiang. Department of Nephrology, the FourthAffiliated Hospital of Guangxi University, Liuzhou 545005, Guangxi, CHINA
      【Abstract】 Objective To observe the relationship between serum or urinary neutrophil gelatinase-associated li-pocalin (NGAL) and apoptosis of renal tubular epithelial cells in the rodent model of cisplatin (DDP) induced acute kid-ney injury (AKI). Methods A total of 36 male Wistar rats were randomly assigned to six groups according to randomnumber table method, with 6 rats in each group. The rats given a single intraperitoneal injected of cisplatin (10 mg/kg) toinduce nephrotoxicity were divided into five groups (CP 12 h group, CP 24 h group, CP 48 h group, CP 96 h group, CP144 h group). The rats in CN group (the control group) were given a single intraperitoneal injection of the same volumeof normal saline vehicle. The pathological changes of renal tissue specimens, serum and urinary NGAL and apoptosis ofrenal tubular apoptosis in each group at each time point were observed, and the correlation was analyzed by Spearmancorrelation. Results Compared with the CN group, CP 12 h group and CP 24 h group showed the pathological charac-teristics of vacuolar degeneration of renal tubular epithelial cells and partial brush border abscission; there was the fur-ther aggravated pathological damage of kidney with the characteristics of visually flat renal tubular epithelial cells, brushborder abscission and lumen dilation in CP 144 h group; The renal apoptotic cells in the CP 12 h group and CP 48 hgroup were respectively (11.5±2.1)/HP and (68.1±11.0)/HP, which were significantly higher than (0.67±0.82)/HP in theCN group (P<0.05); the levels of urinary NGAL of the CP 12 h group was (2.5±0.5) ng/mL, which was significantlyhigher than (1.8±0.4) ng/mL of the CN group (P<0.05); the levels of serum NGAL in the CP 24 h group was (38.5±10.1) ng/mL, which was significantly higher than (17.2±5.2) ng/mL in the CN group (P<0.05); the levels of serum andurinary NGAL in the CP 48 h group were respectively (65.1±6.0) ng/mL and (6.2±1.2) ng/mL, which were significantlyhigher than those in the CN group (P<0.05); Spearman correlation analysis showed that the apoptosis of renal tissue wassignificantly correlated with the expression of serum NGAL (r=0.655, P<0.01) and urinary NGAL (r=0.657, P<0.01).Conclusion Apoptosis may be involved in the early pathogenesis of AKI induced by DDP. NGAL in serum and urinarymay be not only a biomarker of early renal injury, but also may be involved in the pathogenesis of AKI.
      【Key words】 Cisplatin (DDP); Acute kidney injury (AKI); Neutrophil gelatinase-associated lipocalin (NGAL);Pathogenesis; Apoptosis; Necrosis·论 著·doi:10.3969/j.issn.1003-6350.2018.10.003
      基金项目:广西壮族自治区卫计委课

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