经下腔静脉逆灌注对肝移植大鼠早期肾功能的影响

Impact of retrograde hepatic perfusion via the inferior vena cava on early renal functions post-liver- transplantation in rats

目的观察经下腔静脉逆灌注对自体原位肝移植大鼠早期肾功能的影响。方法将70只白体原位肝移植SD大鼠按肝脏的灌注方式不同随机分为经下腔静脉逆灌注组与经门静脉正灌注组，各组35只。各组再随机分成术前对照组、术后6、12、24、48h5个亚组，各亚组7只。经下腔静脉逆灌注组：先开放下腔静脉，再同时开放门静脉与肝动脉；经门静脉正灌注组：先开放门静脉，再依次开放下腔静脉、肝动脉。分别检测两组中各亚组的血清肌酐（Scr）、尿素氮（BUN）、肾损伤分子（KIM）-1及肿瘤坏死因子（TNF）-α水平；取各亚组左肾组织行光镜检查，观察肾组织KIM-1免疫组织化学，计算KIM-1阳性细胞计数。结果两组术前Scr、BUN、K1M-1及TNF—α比较差异无统计学意义（P〉0．05）。与正灌注组比较，术后6、12及24h逆灌注组的Set、BUN及TNF-α水平显著降低[术后6h，Scr：（57．4±14．2）mol／L比（48．0±14．0）mol／L，BUN：（14．1±1．5）mmol／L比（8．0±1．1）mmol／L，TNF-α：（330．1±11．6）ng／L比（294．5±16．2）ng／L；术后12h，Ser：（125．0±40．4）mol／L比（105．4±40．6）mo]／L，BUN：（32．2±2．8）mmol／L比（19．64-2．1）mmol／L；TNF—d：（503．6±46．6）ng／L比（261．8±9．1）ng／L；术后24h，Scr：（57．8±12．6）mol／L比（45．4±11．8）mol／L，BUN：（16．4±3．0）mmol／L比（13．6±3．2）mmol／L，TNF—OL：（408．2±20．9）ng／L比（226．0±21．1）ng／L]；术后48h差异无统计学意义（P〉0．05）；术后6、12、24、48h逆灌注组血清KIM-1水平均显著降低[术后6h，（107．8±2．1）ng／L比（87．3±1．3）ng／L；术后12h，（107．8±2．1）ng／L比（87．3±1．3）ng／L；术后24h，（101．7±1．8）比（81．9±1．6）ng／L；术后48h：（99．7±2．6）,lg／L比（77．5±0．6）ng／L；P〈0．05]，肾组织中KIM．1阳性细胞计数及免疫组织化学评分显著降低（术后6h，40±3比26±2；术后12h，45±3比31±3；术后24h，56±4比35±4；术后48h：60±3比32±2；P〈0．05）。结论经下腔静脉逆灌注可减轻SD大鼠自体原位肝移植术后早期肾功能的损害。

Objective To investigate impactof retrograde hepatic perfusion via the inferior ve- na cava on early renal functions in SD rat models undergoing autologous orthotopic liver transplantation. Methods One group included 35 SD rats undergoing liver transplantation by retrograde hepatic perfusion via the inferior vena cava and the other group included 35 SD rats by hepatic perfusion via the portal vein. Each group was randomly divided into five subgroups as preoperative control, 6 h preoperative, 12 h preop- erative, 24 h preoperative and 48 h preoperative. Each subgroup included 7 rats. For retrograde hepatic perfusion via the inferior vena cava, the anastomosis of inferior vena cava was opened, then those of portal vein and hepatic artery contemporarily. For hepatic perfusion via portal vein, the anastomosis of portal vein was opened, then those of inferior vena cava and hepatic artery in turn. Levels of serum creatinine （ Scr）, blood urea nitrogen （ BUN）, kidney injury molecule-1 （ KIM-1 ） and tumor necrosis factor α （ TNF-α ） were detected in all subgroups. Tissues of the left kidney were taken for light microscopic examination in- cluding observation of KIM-1 immunohistochemistry and calculation of the KIM-1 positive cells. Results There was no significant difference in Scr, BUN, KIM-1 and TNF-α between the two groups preoperatively. The levels of Scr, BUN and TNF-α in the group of hepatic perfusion via portal vein were increased signifi- cantly as compared with those of the group of retrograde hepatic perfusion at 6,12 and 24 h postoperatively （P 〈0. 05）. At 6 h postoperation the values of Scr were （57.4 ±14. 2） versus （48.0 ± 14. 0） mol/L, those of BUN were （14.1 ±1.5） versus （8.0 ± 1.1） mmol/L and those of TNF-c~ （330.1 ± 11.6） versus （ 294. 5 ±16. 2） ng/L respectively in the two group. At 12 h the values of Set were （ 125.0 ±40. 4） versus （105.4±40.6） tool/L, those of BUN were （32.2±2.8） versus （19.6-2.1） mmoL/L and those of TNF-a were （503.6±46. 6） versus （261.8±9. 1 ） ng/L respectively in the two groups. At 24 h the val- uesofSerwere （57.8 --.12.6） versus （45.4-11.8） mol/L, those of BUN were （16.4 ±3.0） versus （ 13.6 ± 3.2） mmol/L and those of TNF-c~ were （408.2 ± 20. 9） versus （226. 0 ＋ 21.1 ） ng/L respective- ly in the two groups. There were significant differences at 48 h postoperation （P 〉 0. 05 ）. The levels of KIM-1, number of KIM-1 positive cells and immunohistoehemieal scores in the group of hepatic peffusion via portal vein were significantly higher than those in the group of retrograde hepatic peffusion at 6, 12, 24 and 48 h postoperation （P 〈0. 05）. At 6 h postoperation, the values of KIM-1 were （ 107.8±2. 1 ） versus （87.3 ＋1.3） ng/L, those at 12 hwere （107.8±2. 1） versus （87.3±1.3） ng/L respectively in the two groups. At 24 h, those were （101.7 ± 1.8） versus （81.9±1.6） ng/L, and （99. 7 ±2.6） ng/L versus （77.5 ±0. 6） ng/L at 48 h in the two groups. The number of KIM-1 positive cells in the two groups at 6 h postoperation was 40 ＋3 versus 26 ±2, that at 12 h was 45 ±3 versus 31 ±3, that at 24 h was 56 --.4 ver- sus 35 -4 and that at 48 h was 60 ± 3 versus 32 ± 2 respectively. Conclusion Retrograde hepatic perfn- sion via the inferior vena cava could significantly reduce the damage of early renal functions in SD rats un- dergoing autologous orthotopic liver transplantation.