N-乙酰半胱氨酸对脑死亡巴马小型猪肝脏的保护作用。

Li J, Zhang S, Wu Y, Guo W, Zhang Y, Zhai W

Department of General Surgery, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.

Transplant Proc. 2010 Jan-Feb;42(1):195-9. doi: 10.1016/j.transproceed.2009.12.039.

OBJECTIVE

To investigate liver injury after brain-death in BA-Ma mini pigs and the protective effects of N-acetylcysteine (NAC) on hepatic function and on nuclear factor (NF)-kappaB mRNA and protein expression.

METHODS

Fifteen Ba-Ma mini pigs were equally divided into three groups at random: brain-dead group (group B), NAC-pretreated group (group N), and control group (group C). A brain-death model was established by increasing intracranial pressure in a modified, slow, and intermittent way. At 6, 12, and 24 hours after the initial brain death, we determined the levels of serum aspartate transferase (AST), alanine transferase (ALT), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. At the same times, hepatic tissue samples were obtained to assess morphological changes in hepatic tissues and the expression of NF-kappaB mRNA and protein was detected by reverse transcriptase polymerase chain reaction and immunohistochemistry, respectively.

RESULTS

The levels of AST and ALT in groups B and N began to increase at 12 hours after brain death; the levels among group N were lower than those in group B (P < .05). The levels of serum IL-1beta, IL-6, and TNF-alpha in group B and group N began to increase gradually at 6 hours after brain death; those of group B were all significantly greater than those among group N at each time (P < .05). The mRNA and protein levels of NF-kappaB among groups B and N began to increase at 6 hours after brain death; however, those of group B were all significantly higher than those of group N (P < .05). Light and electron microscopy showed only mild edema of liver cells in group N. At 12 hours after brain death, mitochondrial swelling and edema in liver cells were observed among group B, with more severe morphological lesions in this group than group N.

CONCLUSIONS

NAC inhibited the degree of NF-kappaB mRNA transcription and its protein translation, decreasing the release of inflammatory factors, and thus alleviating hepatic injury during brain death.

目的

研究巴马小型猪脑死亡后的肝损伤情况以及N - 乙酰半胱氨酸（NAC）对肝功能、核因子（NF）-κB mRNA和蛋白表达的保护作用。

方法

15只巴马小型猪随机均分为三组：脑死亡组（B组）、NAC预处理组（N组）和对照组（C组）。采用改良的缓慢间歇性升高颅内压的方法建立脑死亡模型。在首次脑死亡后6、12和24小时，测定血清天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β和IL - 6水平。同时，获取肝组织样本评估肝组织形态学变化，并分别通过逆转录聚合酶链反应和免疫组织化学检测NF -κB mRNA和蛋白的表达。

结果

B组和N组的AST和ALT水平在脑死亡后12小时开始升高；N组水平低于B组（P <.05）。B组和N组血清IL - 1β、IL - 6和TNF -α水平在脑死亡后6小时开始逐渐升高；各时间点B组均显著高于N组（P <.05）。B组和N组NF -κB的mRNA和蛋白水平在脑死亡后6小时开始升高；然而，B组均显著高于N组（P <.05）。光镜和电镜显示N组仅肝细胞轻度水肿。脑死亡后12小时，B组观察到肝细胞线粒体肿胀和水肿，该组形态学损伤比N组更严重。