高胆红素血症对新生大鼠肾脏的影响

Effect of hyperbilirubinemia on the kidneys of newborn rats

目的了解不同水平的高胆红素血症对新生大鼠肾脏的影响。方法选取7 d龄新生SD大鼠96只,随机分为正常对照组(C组,n=32,腹腔注射生理盐水0.5 ml)、实验1组(T1组,n=32,腹腔注射胆红素溶液100μg/g)和实验2组(T2组,n=32,腹腔注射胆红素溶液200μg/g)。分别设置0 h、8 h、24 h和48 h四个时间点,每个时间点8只大鼠。记录大鼠一般情况,测定每个时间点大鼠血清总胆红素(TSB)、血清肌酐、血清胱抑素C(Cys-C)、血清中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、尿NGAL、尿肾损伤分子1(KIM-1);摘取肾脏制作病理切片,镜下观察肾脏病理学改变。结果T1组和T2组TSB水平在8 h、24 h和48 h均高于0 h(P<0.05),且均在24 h达高峰。8 h后,T1组和T2组的尿NGAL水平均高于C组;24 h后,T2组的尿NGAL水平均高于T1组(P<0.05)。8 h后,T2组尿KIM-1均高于C组和T1组,差异均有统计学意义(P<0.05)。24 h后,T2组血清Cys-C均高于T1组和C组,差异均有统计学意义(P<0.05)。仅T2组大鼠48 h一些肾脏间质血管扩张充血,一些肾小管管腔轻度水肿。结论高胆红素血症可能会损伤大鼠肾小管功能,TSB水平越高,损伤越重;在反映新生鼠肾小管损伤方面,尿KIM-1不如尿NGAL更敏感。高胆红素血症水平较高并持续24~48 h以上时才损伤大鼠肾小球滤过功能,出现肾小管轻微结构性损害;血清NGAL和血清肌酐不如血清Cys-C能更加敏感的反映出肾小球滤过功能的变化。

Objective To understand the effect of different levels of hyperbilirubinemia on the kidneys of newborn rats.Methods Ninety-six 7-day-old newborn SD rats were selected and randomly divided into normal control group(group C,n=32,intraperitoneal injection of normal saline 0.5 ml),test group 1(group T1,n=32,intraperitoneal injection of bilirubin solution 100μg/g),and test group 2(group T2,n=32,intraperitoneal injection of bilirubin solution 200μg/g).Four time-points were set at 0,8 h,24 h,and 48 h,with 8 rats for each time point.The general conditions of the rats were recorded,and the total serum bilirubin(TSB),serum creatinine,serum cystatin C(Cys-C),serum neutrophil gelatinase-associated lipocalin(NGAL),urine NGAL,and urine kidney injury molecule 1(KIM-1)were determined.The kidneys were removed to make pathological sections,and the pathological changes of the kidneys were observed under microscope.Results In group T1 and group T2,the TSB levels of at 8 h,24 h and 48 h were higher than those at 0 h(P<0.05),and peaked at 24 h in both groups.After 8 h,the urine levels of NGAL in groups T1 or T2 were higher than those of group C.After 24 h,the urine levels of NGAL in group T2 were higher than those of group T1(P<0.05).After 8 h,the urine levels of KIM-1 in group T2 were higher than those of groups C or T1(P<0.05).After 24 h,the serum levels of Cys-C in group T2 were higher than those of group T1 or group C(P<0.05).Only at 48 h in group T2 were there dilation and congestion in some renal interstitial blood vessels as well as mild edema in some renal tubules.ConclusionHyperbilirubinemia may damage the renal tubular function of rats.The higher the TSB level was,the more severe the damage was.Urinary KIM-1 was not as sensitive as urine NGAL in reflecting the renal tubular damage of newborn rats.When the level of hyperbilirubinemia was high and lasted for more than 24 to 48 hours,rats glomerular filtration function injury happened with slight structural damage to the renal tubules.Serum NGAL and serum creatinine were not as sensitive as serum Cys-C in reflecting the changes of glomerular filtration function.