猪单侧输尿管梗阻3d及再通后肾脏损伤及修复的动态观察

A porcine model of relief of 3 days unilateral ureteral obstruction： study on the damage and self- repairing capability of the kidney

目的利用单侧输尿管梗阻-再通的实验猪模型，探讨肾小管问质早期损伤能否修复以及修复的时间节点。方法构建猪的单侧输尿管梗阻再通模型：选取8头实验用小型猪，分为5个时间点，分别为梗阻前（0d）、梗阻3d、再通7d、14d及21d。于每个时间点留取梗阻侧和对侧分肾静脉及前腔静脉血，检测其血清肌酐水平；留取肾组织，评估病理损伤一修复情况；Western印迹法测定肾小管间质损伤标志物α-SMA、vimentin和上皮细胞标志物E-cadherin的表达水平。结果梗阻3d时，与梗阻前相比，血肌酐显著升高，肾组织呈现不同程度的损伤，α-SMA、vimentin表达增高而E-cadherin显著下降（P〈0．05）；随着再通时间的延长，血清肌酐水平下降，肾组织损伤逐渐恢复，α-SMA、vimentin表达下调而E-cadherin表达上调（P〈0．05）。结论猪的单侧输尿管梗阻-再通模型为体内研究肾脏损伤修复提供了较好的模型。早期的肾小管间质损伤在病因去除后能够逆转修复。

Objective To explore the reversibility of early stage tubular interstitial injury as well as the timing of reparation through the pig relief of unilateral ureteral obstruction （R-UUO） model. Methods Eight three-month-old female Guangxi BA-MA mini pigs were selected for the construction of R-UUO models. Five time points were set which were UUO 0 day, UUO 3 days, R-UUO 7 days, R-UUO 14 days, and R-UUO 21 days. Renal function, histological structure, and protein expressions of α- smooth muscle actin （or-SMA）, vimentin and E- cadherin were evaluated at different time points. Results After 3 days of UUO, compared with UUO 0 day, serum creatinine levels were increased obviously and the kidney tissues presented varying degrees of damage. The expressions of α-SMA and vimentin were increased and E-cadherin expression was decreased （P 〈 0.05）. Following R-UUO after 3 days of UUO, compared to UUO, serum creatinine levels were significantly decreased. Renal pathological tissue damage was repaired. The expressions of α-SMA and vimentin were decreased and E -cadherin expression was increased （P 〈 0.05）. Conclusions The pig R- UUO animal model may provide a good platform to study the kidney injury and repair. The tubular injury may be fully reversed and repaired when removing the pathogenic factors if the renal tubular injury was at an earlier stage.