多巴胺调控实验性梗阻性黄疸围手术期肾髓质水通道蛋白2表达

Dopamine modulates perioperative renal medulla aquaporin 2 expression in experimental obstructive jaundice

目的:探讨梗阻性黄疸围手术期应用小剂量多巴胺对肾髓质水通道蛋白2(aquaporin 2)蛋白表达影响.方法:♂wistar大鼠70只随机分为4组,分别为对照组(n=10)、梗阻性黄疸组(n=20)、多巴胺5μg组(n=20)和多巴胺10μg组(n=20).梗阻性黄疸组及多巴胺组大鼠全身麻醉后建立梗阻性黄疸动物模型;对照组大鼠行假手术.7d后全麻下解除胆管梗阻,对照组再次行假手术.多巴胺组于胆管再通手术之前于股静脉套管针穿刺泵入多巴胺,剂量分别为5μg/(kg·min)和10μg/(kg·min);而假手术组及梗阻性黄疸组大鼠泵入9g/L生理盐水,泵注持续2h,并将各组动物随机均分为立即取材组和24h后取材组.腔静脉血离心后收集血清冻存检测胆红素、肌酐和尿素氮;分离肾脏髓质冻存,免疫印迹法(Western blotting)法检测aquaporin 2的表达.结果:解除梗阻早期鼠血清胆红素水平下降.血尿素氮及肌酐未见明显改变.通过Western blotting对肾髓质aqp2表达测定发现,梗阻性黄疸组解除梗阻0h取材组aqp2表达较对照组明显下降(15 665±1181 vs 21 966±1544,P<0.01),而解除梗阻24h后aqp2表达出现明显上升(36 490±1822 vs 21 917±2661,P<0.01).多巴胺5μg组0与24h aqp2表达更接近CO组(16 010±646,22 715±575 vs 21 966±1544,21 917±2661);10μg组各时间点aqp2表达与梗黄组接近(13 581±1662,32 313±1453 vs 15 665±1181,36 490±1822),未见多巴胺有明显调节aqp2表达作用.结论:胆管梗阻损伤肾脏集合管上皮细胞结构并抑制水重吸收功能;低浓度多巴胺可调控集合管水通道蛋白2表达.

AIM： To investigate the changes in aquaporin 2 expression after bile duct recanalization and the effects of low-dose dopamine on perioperative renal aquaporin 2 expression. METHODS： Seventy wistar rats were randomly allocated to 4 groups. Sixty rats underwent common bile duct ligation, while the other 10 underwent sham operation. The common duct was ligated on a silicon tube of 2 mm external diameter. Seven days later, the experimental rats were randomly allocated into another 3 groups. Rats in the obstructive jaundice group were injected with 9 g/L normal saline （NS）, while those in the other 2 groups were injected with dopamine at 5 or 10 μg/（kg·min）, respectively. After 2 h treatment, half in each group were killed and the others were killed 24 h later. Serum was collected from each rat to assess hepatic and renal functions. The right renal medulla was separated and kept at -80℃ until used to measure aquaporin 2 expressions by Western blotting. RESULTS： In the early period of bile duct recanalization, serum bilirubin levels decreased. There were no significant changes in blood urine or creatine. Renal aquaporin 2 expression was detected by Western blotting. Aquaporin 2 expression in the experimental group treated with dopamine 5μg/（kg·min） was nearly the same as that in the normal group, both at 0 and 24 h （16 010 ± 646 and 22 715 ± 575 vs 21 966 ± 1544 and 21 917 ± 2661）, and better than the group treated with dopamine 10 μg/（kg·min）. CONCLUSION： Low-dose dopamine injection appears to modulate expression of aquaporin 2 in the renal collective tubule epithelium, and to have a positive effect on perioperative renal function in obstructive jaundice.