帕立骨化醇預處理對大鼠肝缺血再灌注損傷的作用

郝立校，蔡珍福，周玉坤，王堅，陳莉(中國人民解放軍第四五五醫院肝膽外科，上海200052)

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帕立骨化醇預處理對大鼠肝缺血再灌注損傷的作用

郝立校，蔡珍福，周玉坤，王堅，陳莉
(中國人民解放軍第四五五醫院肝膽外科，上海200052)

[摘 要]目的 探討帕立骨化醇預處理對大鼠肝缺血再灌注損傷的保護作用及合理劑量。方法 300只健康雄性SD大鼠隨機分為:假手術組、模型組、實驗1組、實驗2組、實驗3組，每組60只，各實驗組分別于肝缺血再灌注手術前24 h腹腔注射0.15、0.30、0.60 μg/kg帕立骨化醇。每組取20只大鼠于術后3、6、12和24 h取尾靜脈血，并觀察各組此20只大鼠術后24、48、72 h的生存率。各組另40只大鼠分別于術后3、6、12、24 h每個時間點處死10只大鼠，取肝組織。比較各組大鼠存活率和術后谷丙轉氨酶(ALT)、谷草轉氨酶(AST)及肝臟組織丙二醛(MDA)含量。結果 模型組大鼠存活率低于假手術組(P＜0.05)，實驗各組大鼠存活率高于模型組；除實驗1組與模型組相比無統計學意義外，其余各實驗組在術后3、6、12、24 h與模型組相比ALT均有下降(P＜0.05)；而術后3 h起實驗1、2、3組AST水平均低于模型組(P＜0.05)。術后3、6、12、24 h，各實驗組肝組織MDA均低于模型組，實驗2組和3組與實驗1組差異具有統計學意義(P＜0.05)，實驗2組與實驗3組間差異無統計學意義(P＞0.05)。結論 帕立骨化醇預處理對大鼠肝缺血再灌注損傷具有保護作用，0.15 μg/kg即可以明顯改善模型肝功和肝臟MDA水平，但0.30 μg/kg以上水平效果更佳。

[關鍵詞]帕立骨化醇；肝臟缺血再灌注損傷；谷丙轉氨酶；谷草轉氨酶；丙二醛

Pretreatment effect of Paricalcitol on hepatic ischemia-reperfusion injury in rats HAO Li-xiao, CAI Zhen-fu, ZHOU Yu-kun, WANG Jian, CHEN Li.Department of Hepatobiliary Surgery, the 455thHospital of People’s Liberation Army, Shanghai 200052, China

Abstract ObjectiveTo explore the pretreatment effect of paricalcitol on hepatic ischemia reperfusion damage and explore reasonable dosage.MethodsThree hundred healthy male SD rats were randomly divided into sham group (n=60), model group (n=60), test 1 group (n=60), test 2 group (n=60) and test 3 group (n=60).Rats of test group were intraperitoneal injection with 0.15 μg/kg, 0.30 μg/kg, 0.60 μg/kg of Paricalcitol respectively 24 h before reperfusion.Twenty rats’ venous blood samples were taken at 3, 6, 12, 24 h after operation in each group, and the survival rates were observed at 24 h, 48 h, 72 h after operation.Ten of the other forty rats were sacri■ced for liver tissue at 3, 6, 12, 24 h after operation in each group.All groups of rats were compared with the survival rates, levels of ALT, AST and MDA in liver tissue.ResultsThe survival rate in model group was lower than that in sham group (P＜0.05), survival rate of all test groups 1, 2 and 3 was signi■cantly lower than that in model group (P＜0.05).Except test group 1, ALT levels of test 2 and 3were lower than that in model group 3 h postoperative (P＜0.05).Levels of AST in test group were lower than the model group 3 h postoperatively (P＜0.05).Levels of MDA in liver tissue in test groups 1, 2 and 3 were lower than model group 3～24 h postoperatively.Levels of MDA in liver tissue test group 2 and 3 showed statistically difference (P＜0.05) with that in test group 1, but levels of MDA in liver tissue showed no signi■cant difference between test group 2 and 3 (P＞0.05).ConclusionParicalcitol pretreatment possesses protective effects on hepatic ischemia-reperfusion injury.Dosage of 0.15 μg/kg can obviously improve the model and hepatic MDA level, and more than 0.30 μg/kg level affects better.

Key words Paricalcitol； hepatic ischemia-reperfusion injury； ALT； AST； MDA

肝臟缺血再灌注損傷(hepatic ischemiareperfusion，HIRI)的發生與缺血再灌注過程中氧自由基釋放、肝臟能量代謝障礙、細胞內鈣離子超載、微循環功能障礙、細胞因子、線粒體功能異常、Kupffer細胞激活及中性粒細胞的活化等因素有關[1-3]。……