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选择性抑制初始细胞因子反应有助于大鼠广泛肝切除术后的肝脏再生。

Selective suppression of initial cytokine response facilitates liver regeneration after extensive hepatectomy in rats.

作者信息

Tsutsumi Ryuji, Kamohara Yukio, Eguchi Susumu, Azuma Takashi, Fujioka Hikaru, Okudaira Sadayuki, Yanaga Katsuhiko, Kanematsu Takashi

机构信息

Department of Transplantation and Digestive Surgery, Graduate School of Biomedical Science, Nagasaki University, Nagasaki, Japan.

出版信息

Hepatogastroenterology. 2004 May-Jun;51(57):701-4.

Abstract

BACKGROUND/AIMS: After extensive hepatectomy, the cytokine network plays an important role in injury to the remnant liver and subsequent impairment of liver regeneration. Tumor necrosis factor alpha (TNF alpha) and interleukin 1beta (IL-1beta) are thought to be the initial cytokines associated with liver injury as well as with regeneration. We investigated the effect of the suppression of these cytokines on liver function and on liver regeneration after subtotal hepatectomy in rats.

METHODOLOGY

Following 90% hepatectomy, rats were divided into two groups. Animals in the FR group received intraperitoneal FR167653, a selective inhibitor of TNF alpha and IL 1beta, while those in the Control group received vehicle only. Liver chemistry and serum levels of TNF alpha and IL-6 were measured serially. Liver specimens were obtained 48 hr after surgery and regenerative activity assessed by proliferating cell nuclear antigen (PCNA) expression and remnant liver weight.

RESULTS

The survival rate was significantly better in the FR group (76.4+/-11.7 hrs) than in the Control group (26.8+/-4.3 hrs, p=0.0014). Liver enzyme and blood sugar levels after surgery were higher in the FR group compared to the Control group (p=0.03 or less). Changes in serum levels of both TNF alpha and IL-6 were suppressed in FR group rats after surgery. Microscopically, hepatocellular damage and steatosis was less prominent in FR group livers. PCNA labeling index and residual liver weights were higher in the FR group (p<0.001).

CONCLUSIONS

Following extensive hepatectomy in rats, suppression of early cytokine induction improved liver function and facilitated liver regeneration. Suppression of selective cytokine responses could allow extended liver resection and reduced risk of liver failure.

摘要

背景/目的:在广泛肝切除术后,细胞因子网络在残余肝损伤及随后的肝再生受损过程中发挥重要作用。肿瘤坏死因子α(TNFα)和白细胞介素1β(IL-1β)被认为是与肝损伤以及再生相关的起始细胞因子。我们研究了抑制这些细胞因子对大鼠肝切除术后肝功能和肝再生的影响。

方法

在90%肝切除术后,将大鼠分为两组。FR组动物腹腔注射FR167653,一种TNFα和IL-1β的选择性抑制剂,而对照组动物仅接受溶剂。连续测量肝功能指标以及TNFα和IL-6的血清水平。术后48小时获取肝脏标本,并通过增殖细胞核抗原(PCNA)表达和残余肝重量评估再生活性。

结果

FR组的生存率(76.4±11.7小时)显著高于对照组(26.8±4.3小时,p = 0.0014)。与对照组相比,FR组术后肝酶和血糖水平更高(p = 0.03或更低)。术后FR组大鼠血清中TNFα和IL-6水平的变化受到抑制。显微镜下,FR组肝脏中肝细胞损伤和脂肪变性不那么明显。FR组的PCNA标记指数和残余肝重量更高(p < 0.001)。

结论

在大鼠广泛肝切除术后,抑制早期细胞因子诱导可改善肝功能并促进肝再生。抑制选择性细胞因子反应可允许扩大肝切除术并降低肝衰竭风险。

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