马兜铃酸和庆大霉素对大鼠急性肾小管坏死模型肾组织氧合水平的影响

Abstract

目的 探讨马兜铃酸(AA)及庆大霉素所致急性肾小管坏死(ATN)大鼠的肾组织氧合水平特点.方法 28只健康雄性Wistar大鼠随机分为对照组(n=12)、马兜铃酸钠模型组(AAN组,n=7)和庆大霉素组(GM组,n=9),分别背部皮下注射生理盐水、马兜铃酸钠盐生理盐水溶液(AA-I25 mg·kg-1·d-1)和庆大霉素(200 ng·kg-1·d-1)共4 d,于给药后第7天处死.给药后第4天及第7天行大鼠肾脏BOLD MR成像,并留取血、尿及肾脏标本,观察肾功能及肾脏病理改变.结果 AAN组大鼠第7天时血肌酐及尿NAG酶水平显著增高,肾脏病理结果显示,病变部位主要位于皮髓交界区,表现为肾小管弥漫性坏死,无间质水肿或炎细胞浸润.BOLD-MRI显示,AAN组与对照组相比,肾髓质R2*在第4天[(50.6±15.6)/s vs(35.6±4.3)/s,P＜0.01)和第7天[(58.4±14.8)/svs(37.8±3.6)/s,P＜0.01)均显著升高,肾皮质R2*在第7天较对照组显著升高[(40.3±14.7)/svs(28.7±3.2)/s,P＜0.05].GM组大鼠第7天时血肌酐及尿NAG酶水平均显著升高,但其肾脏R2*变化趋势与AAN组明显不同,主要表现为肾皮质R2*值在第7天较对照组明显降低[(17.7±2.7)/s vs(28.7±3.2)/s,P＜0.01].结论 急性AAN大鼠模型中肾组织存在缺氧,其特征为肾髓质的氧合水平降低早期出现并持续存在,肾皮质的氧合水平在后期逐渐降低,AAN与GM所致ATN有所不同,可能是促进肾间质纤维化持续进展的原因之一.

To investigate the characteristics of renal oxygenation status in aristolochic acids I (AA-I) induced ATN rat model by method of blood oxygenation level-dependent MRI (BOLD-MRI) and compare it with ATN model caused by gentamicin.28 male Wistar rats were randomly divided into control, AAN and GM groups, which were subcutaneously injected with normal saline, AA-I (25 mg x kg(-1)x d(-1)) or GM (200 mg x kg(-1)x d(-1)) respectively for 4 days. Intrarenal oxygenation was measured by BOLD-MRI at 4(th) day and 7(th) day. Renal histopathological changes and renal function were also observed at day 7.Serum level of creatinine and urinary NAG were obviously elevated at day 7 in AAN and gentamicin group. Diffuse tubular necrosis confined to the margin of renal cortex and medulla without edema or infiltration of inflammation cells was the main pathological finding in AAN group. BOLD-MRI revealed that renal medullar R2(*) was elevated significantly at both day 4 [(50.6 +/- 15.6)/s vs (35.6 +/- 4.3)/s, P < 0.01] and day 7 [(58.4 +/- 14.8)/s vs (37.8 +/- 3.6)/s, P < 0.01] in AAN group when compared to control, showing opposite changes to GM group whose R2(*) was decreased at the same time. In addition, the renal cortical R2(*) in AAN group was also higher than that of control [(40.3 +/- 14.7)/s vs (28.7 +/- 3.2)/s, P < 0.05] at day 7, showing opposite changes to GM group.Intrarenal hypoxia exists in acute AAN rats, which initiates in the medulla following an involvement in renal cortex. The phenomenon of persistent low level of intrarenal oxygenation is different from change of GM-induced ATN, which may contribute to the progression of renal interstitial fibrosis in AAN.