CAJ | 학술논문

目的观察钠钙交换蛋白(Na+/Ca2+ exchanger,NCX)抑制剂KB-R7943对造影剂致急性肾损伤(CI-AKI)大鼠的影响.方法雄性Wistar大鼠24只,计算机随机法分成4组:正常对照组、CI-AKI组及5、10 mg/kg KB-R7943治疗组,每组6只.造影剂注射后1d测定大鼠肾功能及肾血流动力学变化；TUNEL法检测肾小管上皮细胞凋亡；放免法测定肾组织内皮素1(ET-1)水平.肾组织丙二醛(MDA)及过氧化氢酶(CAT)水平作为肾组织氧化指标.反转录PCR检测肾组织NCX1mRNA表达.结果 CI-AKI组大鼠血肌酐显著高于对照组及5、10 mg/kg KB-R7943治疗组[(149±35)比(55±4)、(69±11)、(60±3)μmol/L,均P＜0.05].CI-AKI组大鼠肾血管阻力指数、肾组织ET-1、MDA及CAT水平均显著高于对照组及5、10 mg/kg KB-R7943治疗组.病理及TUNEL结果显示5、10 mg/kg KB-R7943治疗组的肾小管上皮细胞坏死与凋亡显著轻.对照组、CI-AKI及10 mg/kgKB-R7943治疗组大鼠NCXl mRNA表达差异无统计学意义.结论肾小管上皮细胞NCX反向转运介导的肾组织氧化应激增加及ET-1过度生成参与CI-AKI的发病；抑制肾小管上皮细胞NCX反向转运对CI-AKI有保护作用.
목적 관찰납개교환단백(Na+/Ca2+ exchanger,NCX)억제제KB-R7943대조영제치급성신손상(CI-AKI)대서적영향.방법 웅성Wistar대서24지,계산궤수궤법분성4조:정상대조조、CI-AKI조급5、10 mg/kg KB-R7943치료조,매조6지.조영제주사후1d측정대서신공능급신혈류동역학변화；TUNEL법검측신소관상피세포조망；방면법측정신조직내피소1(ET-1)수평.신조직병이철(MDA)급과양화경매(CAT)수평작위신조직양화지표.반전록PCR검측신조직NCX1mRNA표체.결과 CI-AKI조대서혈기항현저고우대조조급5、10 mg/kg KB-R7943치료조[(149±35)비(55±4)、(69±11)、(60±3)μmol/L,균P＜0.05].CI-AKI조대서신혈관조력지수、신조직ET-1、MDA급CAT수평균현저고우대조조급5、10 mg/kg KB-R7943치료조.병리급TUNEL결과현시5、10 mg/kg KB-R7943치료조적신소관상피세포배사여조망현저경.대조조、CI-AKI급10 mg/kgKB-R7943치료조대서NCXl mRNA표체차이무통계학의의.결론 신소관상피세포NCX반향전운개도적신조직양화응격증가급ET-1과도생성삼여CI-AKI적발병；억제신소관상피세포NCX반향전운대CI-AKI유보호작용.
Objective Intracellular Ca2+ overload is a key factor in contrast-induced renal tubular toxicity.Na +/Ca2 + exchanger (NCX) system is one of main pathways of intracellular Ca2 + overload.We explore the effects of KB-R7943,an inhibitor of reverse mode of NCX,on contrast-induced acute kidney injury (CI-AKI).Methods Rats were divided into control,CI-AKI and pre-treatment groups with KB-R7943 (5,10 mg/kg).CI-AKI was induced by diatrizoate administration in rats with cholesterolsupplemented diet for 8 weeks.Renal function and hemodynamics were determined at Day 1 postadministration.Renal histopathology was observed under light microscope.Renal tubular apoptosis was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).Renal endothelin-1 (ET-1) was measured by radioimmunoassay.The oxidative markers of renal malondialdehyde (MDA) and catalase (CAT) were measured.The expression of NCX was evaluated by reverse transcription-polymerase chain reaction (RT-PCR).Results Levels of serum creatinine (Scr,μmol/L) in CI-AKI rats ((149 ±35) μmol/L) were significantly higher than those of normal rats ((55 ± 4) μmol/L,P ＜ 0.01).Renal ET-1,MDA and CAT,resistance index (RI) of renal blood vessels increased significantly in CI-AKI rats.The contrast-induced increases in Scr and RI of renal blood vessels were suppressed significantly and dosedependently by pretreatment with KB-R7943.Histopathological and TUNEL results showed that contrastinduced severe renal tubular necrosis and apoptosis were significantly and dose-dependently attenuated by KB-R7943.KB-R7943 significantly suppressed the contrast-induced increments of ET-1,MDA and CAT.No significant changes in NCX1 mRNA expression were observed following contrast administration.Conclusion Renal oxidative stress and ET-1 overproduction via the activation of reverse mode of NCX play an important role in the pathogenesis of CI-AKI.And inhibition of reverse mode of NCX expressed in renal tubular epithelial cell has protective effects on CI-AKI.