美司钠可维持肝射频消融术联合肝门阻断时肝细胞的再生能力。

Laboratory of Experimental Surgery and Surgical Research, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.

J Surg Res. 2011 Jul;169(1):44-50. doi: 10.1016/j.jss.2009.10.001. Epub 2009 Oct 25.

BACKGROUND

The objectives of the present study were to test the hypothesis that hepatocyte regenerating activity induced by radiofrequency ablation (RFA) of the liver is attenuated when performed under Pringle maneuver, and to investigate the potentially protective effect of mesna prophylactic administration.

MATERIALS AND METHODS

Wistar rats were subjected to liver RFA (group RFA), RFA plus Pringle maneuver for 30 min (group RFA+P), RFA plus Pringle plus mesna (400mg/kg, per os, 3h prior to operation) (group RFA+P+M), Pringle only (group P), or sham operation (group S) after midline laparotomy. At 1h, liver oxidative state (glutathione to glutathione disulfide ratio-GSH/GSSG) and nuclear factor κB (NF-κB) activity were assessed in liver specimens. At 1, 3, and 6h, the levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured in blood serum. At 24h, 48 h, 1 wk, and 3 wk, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured in blood serum and the histopathologic profile and hepatocyte mitotic activity were assessed in liver specimens.

RESULTS

Mitotic activity was low but sustained in groups RFA and RFA+P+M, more intense in group P, while suppressed in group RFA+P. Histopathologic profile was deteriorated with lesions being more intense in group RFA+P but significantly less severe in group RFA+P+M. Oxidative stress was equally induced in all experimental groups. NF-κB was activated in groups RFA, RFA+P, and P, but not in group RFA+P+M. IL-6 and TNF-α serum levels were increased; the levels were significantly higher in group RFA+P, while lower in group RFA+P+M. Serum transaminases levels were increased during the first 48 h.

CONCLUSIONS

Hepatocyte regenerating activity is suppressed following liver RFA under Pringle maneuver. Prophylactic administration of mesna preserves hepatocyte regenerating capacity by attenuating acute inflammatory response and minimizing hepatic tissue injury in the non-ablated liver parenchyma.

背景

本研究的目的是验证肝射频消融（RFA）时施行 Pringle 手法会减弱肝再生活性的假说，并研究美司钠预防性给药的潜在保护作用。

材料和方法

Wistar 大鼠行肝 RFA（RFA 组）、RFA 加 30min Pringle 手法（RFA+P 组）、RFA 加 Pringle 手法加美司钠（400mg/kg，口服，术前 3h）（RFA+P+M 组）、仅施行 Pringle 手法（P 组）或剖腹术假手术（S 组）。在 1h 时，评估肝组织标本的氧化状态（谷胱甘肽与谷胱甘肽二硫化物比值-GSH/GSSG）和核因子 κB（NF-κB）活性。在 1、3 和 6h 时，测量血清中白细胞介素 6（IL-6）和肿瘤坏死因子 α（TNF-α）的水平。在 24h、48h、1 周和 3 周时，测量血清中天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）的水平，并评估肝组织标本的组织病理学特征和肝细胞有丝分裂活性。

结果

RFA 组和 RFA+P+M 组的有丝分裂活性低但持续，P 组的有丝分裂活性较强，而 RFA+P 组的有丝分裂活性受到抑制。组织病理学特征在 RFA+P 组恶化，但在 RFA+P+M 组显著减轻。所有实验组的氧化应激均被诱导。RFA、RFA+P 和 P 组 NF-κB 被激活，但 RFA+P+M 组未被激活。血清 IL-6 和 TNF-α 水平升高；RFA+P 组水平显著升高，而 RFA+P+M 组水平较低。在最初的 48h 内，血清转氨酶水平升高。