Glycine Pretreatment Ameliorates Liver Injury After Partial Hepatectomy in the Rat
Glycine Pretreatment Ameliorates Liver Injury After Partial Hepatectomy in the Rat
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DOI：
10.3109/08941930903469466
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发表时间：
2010-02-01
影响因子：
1.9
通讯作者：
Rauen, Ursula
中科院分区：
文献类型：
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作者：
Benko, Tamas;Frede, Stilla;Rauen, Ursula
背景：活体肝移植受试者需接受肝切除术。在手术过程中，需要对肝脏进行药理学或营养学保护，以确保残留物能够保持足够的功能。我们研究的目的是分析在大鼠模型中用α-生育酚（维生素E）、类黄酮水飞蓟宾和/或氨基酸L-甘氨酸预处理对供体的影响。研究方法：将雄性Wistar大鼠用L-甘氨酸（在食物中5%，5天）、α-生育酚（100 mg/kg体重，通过管饲，3天）和/或水飞蓟宾（100 mg/kg体重，i. p.，5天）。此后，90%的肝部分切除术没有门静脉阻断。结果如下：甘氨酸预处理显著降低转氨酶释放（AST，12小时：甘氨酸1292 +/- 192 U/L，对照2311 +/- 556 U/L，p < .05; ALT，12小时：甘氨酸1013 +/- 278 U/L，对照2038 +/- 500 U/L，p < .05）、血清ALP活性和血清胆红素水平（p < .05）。凝血酶原时间缩短，组织学上，甘氨酸组的肝损伤也减少。水飞蓟宾预处理不太有利，并且在该非常高的剂量下用α-生育酚预处理显示出一些不利影响。合并，即，三重预处理不如单独甘氨酸有利。肝切除诱导HIF-1 α积累，甘氨酸预处理也降低HIF-1 α积累。结论：甘氨酸预处理后肝损伤的减少和肝功能的改善表明，甘氨酸预处理可能是有益的活肝供体以及由于其他原因进行部分肝切除术的患者。
Background: Living donor liver transplantation subjects the donor to a major hepatectomy. Pharmacological or nutritive protection of the liver during the procedure is desirable to ensure that the remnant is able to maintain sufficient function. The aim of our study was to analyze the effects of pretreatments with alpha-tocopherol (vitamin E), the flavonoid silibinin and/or the amino acid L-glycine on the donor in a rat model. Methods: Male Wistar rats were pretreated with L-glycine (5% in chow, 5 days), alpha-tocopherol (100 mg/kg body weight by gavage, 3 days) and/or silibinin (100 mg/kg body weight, i.p., 5 days). Thereafter, 90% partial hepatectomy was performed without portal vein clamping. Results: Glycine pretreatment markedly decreased transaminase release (AST, 12 hr: glycine 1292 +/- 192 U/L, control 2311 +/- 556 U/L, p < .05; ALT, 12 hr: glycine 1013 +/- 278 U/L, control 2038 +/- 500 U/L, p < .05), serum ALP activity and serum bilirubin levels (p < .05). Prothrombin time was reduced, and histologically, liver injury was also decreased in the glycine group. Silibinin pretreatment was less advantageous and pretreatment with alpha-tocopherol at this very high dose showed some adverse effects. Combined, i.e., triple pretreatment was less advantageous than glycine alone. Liver resection induced HIF-1 alpha accumulation and HIF-1 alpha accumulation was also decreased by glycine pretreatment. Conclusion: The decrease of liver injury and improvement of liver function after pretreatment with glycine suggests that glycine pretreatment might be beneficial for living liver donors as well as for patients subjected to partial hepatectomy for other reasons.