Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
Chin Med J (Engl). 2011 Feb;124(4):574-80.
Donor-pretreatment with ulinastatin may influence the liver graft during cold preservation. The aim of this research was to determine whether pretreatment of donor liver with Ulinastatin can attenuate cold preservation injury, and to explore the mechanism by which Ulinastatin affects the donor liver graft.
One hundred and forty-four Wistar rats were divided into the Ulinastatin treatment group (T group) pretreated with Ulinastatin 50 000 U/kg and control group (C group) treated with 0.9% normal saline via peritoneal injection prior to the anesthetization. After the abdominal cavity was opened and perfused with cold Ringer's lactate solution, the liver was harvested. The harvested liver was preserved in cold Ringer's lactate solution for 0, 2, 6, 24 hours, at which time the liver tissue was sampled for determination of dry weight and wet weight, Na(+)-K(+)-ATPase and Ca(2+)-ATPase activity, lactic acid dehydrogenase (LDH) activity, lactic acid and malondialdehyde levels. Light microscopy and electron microscopy were used to observe liver morphology. The liver cold-preservation solution was taken for measurement of aspartate aminotransferase (AST) and alanine transaminase (ALT) levels. Correlation between ATPase activity and lactic acid level was analyzed by SPSS 13.0 for Windows.
The morphology in the T group had improved cell boundaries vs. the C group at each time point. Dry weight to wet weight in the T group was lower than in the C group at 6 hours (P < 0.05), but the difference was not significant at 24 hours. ALT levels in the T group were lower than that in the C group at 6 hours (P < 0.05) and 24 hours (P < 0.01). AST levels in the T group were lower than those in the C group at 2 hours (P < 0.05), 6 hours (P < 0.01) and 24 hours (P < 0.01). Na(+)-K(+)-ATPase activity in the T group was higher than in the C group and the mean difference between two groups was significant at 0 hour (P < 0.05) and 2 hours (P < 0.05). Ca(2+)-ATPase activity in the T group was higher than in the C group with the mean difference between two groups significant at 2 hours (P < 0.05). The T group had increased lactic acid levels at 0 hour (P < 0.01) and 2 hours (P < 0.05) compared with the C group, but there was no influence on the LDH activity at the same time. There were no obvious differences in the levels of malondialdehyde between the two groups at any time point. A linear correlation between Na(+)-K(+)-ATPase activity and lactic acid levels (r = 0.295, P < 0.05) was found.
Donor-pretreatment with ulinastatin may protect the cells in a liver graft from ischemia injury during cold preservation; the mechanism may be due to its promotion for cell glycolysis and its preservation of ATPase activity.
供体预处理乌司他丁可能会影响冷保存期间的肝移植物。本研究的目的是确定供体肝预处理乌司他丁是否可以减轻冷保存损伤，并探讨乌司他丁影响供体肝移植物的机制。
将 144 只 Wistar 大鼠分为乌司他丁治疗组（T 组）和对照组（C 组）。在麻醉前，T 组通过腹腔注射乌司他丁 50 000 U/kg，C 组注射 0.9%生理盐水。开腹并灌注冷林格氏乳酸盐溶液后，采集肝脏。采集的肝脏在冷林格氏乳酸盐溶液中保存 0、2、6、24 小时，同时采集肝组织测定干重和湿重、Na(+)-K(+)-ATP 酶和 Ca(2+)-ATP 酶活性、乳酸脱氢酶（LDH）活性、乳酸和丙二醛水平。用光镜和电子显微镜观察肝形态。取肝冷保存液检测天门冬氨酸氨基转移酶（AST）和丙氨酸氨基转移酶（ALT）水平。采用 SPSS 13.0 for Windows 对 ATP 酶活性与乳酸水平进行相关性分析。
T 组在各个时间点的细胞边界形态均优于 C 组。T 组在 6 小时时的干重/湿重比值低于 C 组（P < 0.05），但 24 小时时差异无统计学意义。T 组 ALT 水平在 6 小时（P < 0.05）和 24 小时（P < 0.01）时低于 C 组。T 组 AST 水平在 2 小时（P < 0.05）、6 小时（P < 0.01）和 24 小时（P < 0.01）时低于 C 组。T 组 Na(+)-K(+)-ATP 酶活性高于 C 组，两组间平均差异在 0 小时（P < 0.05）和 2 小时（P < 0.05）时具有统计学意义。T 组 Ca(2+)-ATP 酶活性高于 C 组，两组间平均差异在 2 小时（P < 0.05）时具有统计学意义。T 组在 0 小时（P < 0.01）和 2 小时（P < 0.05）时乳酸水平升高，而同时 LDH 活性无明显影响。两组在任何时间点的丙二醛水平均无明显差异。Na(+)-K(+)-ATP 酶活性与乳酸水平呈线性相关（r = 0.295，P < 0.05）。
供体预处理乌司他丁可能会保护冷保存期间肝移植物中的细胞免受缺血损伤；其机制可能是通过促进细胞糖酵解和保持 ATP 酶活性来实现的。
