Koo Ja Wook, Kim Youngki, Rozen Silvia, Mauer Michael
Department of Pediatrics, Sanggye Paik Hospital, Inje University, Seoul, Korea.
J Nephrol. 2003 Mar-Apr;16(2):203-9.
Complete ureteral obstruction in rats rapidly leads to renal interstitial expansion and fibrosis and this process is ameliorated by concomitant angiotensin converting enzyme inhibition (ACEI). However, models of intervention initiated after unilateral ureteral obstruction (UUO) release may be more analogous to human obstructive renal disease where treatment could more reasonably follow the discovery of obstructive uropathy as compared to models where treatment is initiated at the time of experimentally induced obstruction. We studied interstitial changes in rats before and after release of UUO and examined the effect of ACEI with 200mg/L of enalapril (E) in the drinking water on these changes. Rats were sacrificed after 10 (n=10) and 20 (n=10) days (D) of UUO or 10D after release of 10D of UUO (n=18). Eleven rats received E for 10D after UUO release. Cortical interstitial volume fraction [Vv(I/C)] measured by point counting was increased at 10D (0.32 +/- 0.05) and 20D (0.41 +/- 0.05) of UUO compared to contralateral and sham-operated kidneys (both 0.05 +/- 0.01, ANOVA, p <0.001). Vv(I/C) 10D after release from 10D of UUO (0.26 +/- 0.04) was lower than that of 10D of UUO (p<0.05) and much lower than those with 20D of UUO (p<0.001). However, rats treated with E from the time of UUO release had lower Vv(I/C) (0.21 +/- 0.07) than UUO released E untreated rats (p<0.05). Release of UUO initiates regression of interstitial expansion in rats. ACEI with enalapril significantly accelerates reversal of interstitial expansion after UUO release. This could have important implications for treatment of obstructive nephropathy in humans.
大鼠输尿管完全梗阻会迅速导致肾间质扩张和纤维化，而血管紧张素转换酶抑制（ACEI）可改善这一过程。然而，与在实验性诱导梗阻时开始治疗的模型相比，单侧输尿管梗阻（UUO）解除后启动干预的模型可能更类似于人类梗阻性肾病，在人类梗阻性肾病中，治疗可在发现梗阻性尿路病后更合理地进行。我们研究了UUO解除前后大鼠的间质变化，并检测了饮用水中含200mg/L依那普利（E）的ACEI对这些变化的影响。在UUO 10天（n = 10）和20天（n = 10）后或10天UUO解除后10天（n = 18）处死大鼠。11只大鼠在UUO解除后接受E治疗10天。与对侧和假手术肾脏相比（均为0.05±0.01，方差分析，p<0.001），在UUO 10天（0.32±0.05）和20天（0.41±0.05）时，通过点计数测量的皮质间质体积分数[Vv（I/C）]增加。从10天UUO解除后10天的Vv（I/C）（0.26±0.04）低于10天UUO时（p<0.05），且远低于20天UUO时（p<0.001）。然而，从UUO解除时开始用E治疗的大鼠的Vv（I/C）（0.21±0.07）低于未用E治疗的UUO解除大鼠（p<0.05）。UUO解除可启动大鼠间质扩张的消退。依那普利ACEI可显著加速UUO解除后间质扩张的逆转。这可能对人类梗阻性肾病的治疗具有重要意义。
