Li Shadan, Liu Bin, Guan Qiunong, Chafeeva Irina, Brooks Donald E, Nguan Christopher Yc, Kizhakkedathu Jayachandran N, Du Caigan
Department of Urology, Chengdu Military General HospitalChengdu, Sichuan, China; Department of Urologic Sciences, University of British ColumbiaVancouver, BC, Canada.
Department of Urologic Sciences, University of British ColumbiaVancouver, BC, Canada; Department of Critical Care Medicine, General Hospital of Tianjin Medical UniversityTianjin, China.
Am J Transl Res. 2017 Feb 15;9(2):429-441. eCollection 2017.
Minimizing donor organ injury during cold preservation (including cold perfusion and storage) is the first step to prevent transplant failure. We recently reported the advantages of hyperbranched polyglycerol (HPG) as a novel substitute for hydroxyethyl starch in UW solution for both cold heart preservation and cold kidney perfusion. This study evaluated the functional recovery of the kidney at reperfusion after cold preservation with HPG solution. The impact of HPG solution compared to conventional UW and HTK solutions on tissue weight and cell survival at 4°C was examined using rat kidney tissues and cultured human umbilical vein endothelial cells (HUVECs), respectively. The kidney protection by HPG solution was tested in a rat model of cold kidney ischemia-reperfusion injury, and was evaluated by histology and kidney function. Here, we showed that preservation with HPG solution prevented cell death in cultured HUVECs and edema formation in kidney tissues at 4°C similar to UW solution, whereas HTK solution was less effective. In rat model of cold ischemia-reperfusion injury, the kidneys perfused and subsequently stored 1-hour with cold HPG solution showed less leukocyte infiltration, less tubular damage and better kidney function (lower levels of serum creatinine and blood urea nitrogen) at 48 h of reperfusion than those treated with UW or HTK solution. In conclusion, our data show the superiority of HPG solution to UW or HTK solution in the cold perfusion and storage of rat kidneys, suggesting that the HPG solution may be a promising candidate for improved donor kidney preservation prior to transplantation.
在冷保存(包括冷灌注和储存)期间将供体器官损伤降至最低是预防移植失败的第一步。我们最近报道了超支化聚甘油(HPG)作为UW溶液中羟乙基淀粉的新型替代品在冷心脏保存和冷肾灌注方面的优势。本研究评估了用HPG溶液冷保存后再灌注时肾脏的功能恢复情况。分别使用大鼠肾脏组织和培养的人脐静脉内皮细胞(HUVECs)研究了HPG溶液与传统UW和HTK溶液相比在4°C下对组织重量和细胞存活的影响。在大鼠冷肾缺血再灌注损伤模型中测试了HPG溶液的肾脏保护作用,并通过组织学和肾功能进行评估。在此,我们表明,与UW溶液类似,用HPG溶液保存可防止培养的HUVECs细胞死亡和4°C时肾脏组织水肿形成,而HTK溶液效果较差。在大鼠冷缺血再灌注损伤模型中,与用UW或HTK溶液处理的肾脏相比,用冷HPG溶液灌注并随后储存1小时的肾脏在再灌注48小时时白细胞浸润更少、肾小管损伤更少且肾功能更好(血清肌酐和血尿素氮水平更低)。总之,我们的数据表明HPG溶液在大鼠肾脏的冷灌注和储存方面优于UW或HTK溶液,这表明HPG溶液可能是移植前改善供体肾脏保存的有前途的候选者。