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Implication of intestinal lymphocytes in endotoxin-induced hepatic injury after partial hepatectomy in rats

肠淋巴细胞在大鼠肝部分切除术后内毒素性肝损伤中的意义

基本信息

批准号：
15591396
负责人：
NAKAMURA Toshio
金额：
$ 2.05万
依托单位：
Hamamatsu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

Lymphocyte population constitutes major defense mechanism against endotoxemia, but the role of B lymphocytes in endotoxin-induced hepatic injury after hepatectomy is not clear. We employed lymphopenic (L(-)) rats by single administration of anti-rat lymphocyteserum, nu/nu athymic (T(-)) rats, B cell-ablated (B(-))rats by intermittent injection of anti-immunoglobulin (Ig) m-chain from birth, and their vehicle controls. These animals weresubjected to two-thirds hepatectomy with subsequent intravenous lipopolysaccharides (LPS, 1.5mg/kg) administration. The survival rate, plasma alanine transaminase (ALT), tumor necrosisfactor-a (TNF-α) and IgM levels, and total hemolytic activity (CH50) were determined. Hepatictissue deposition of IgM or C3 was assessed with immunohistochemistry. Results. The 24-hour survival rate in control animals was 20%, whereas those in L(-), T(-), and B(-) animals were 80%,0% and 100 %, respectively. Lymphocyte-sufficient control (L(+)) and Bcell-sufficient control (B(+)) animals showed a rapid elevation of plasma TNF-a levels 1 hour after the challenge, followed by an increase in plasma ALT levels. In B(+) group, plasma IgM levels were increased and CH50 activities were decreased 4 hours after LPS injection with significant difference compared to those at time 0. Liver histology showed massive hepatic necrosis with a dense accumulation of IgM and C3 deposits 4 hours after LPS administration. B cell ablation significantly ameliorated plasma ALT, IgM and CH50 levels, showing less histological liver damage. Conclusion. B lymphocytes susceptible to LPS might be implicated in the development of endotoxin-induced hepatic injury after partial hepatectomy. The result of our research will be published in Journal of Surgical Research.

淋巴细胞群是内毒素血症的主要防御机制，但B淋巴细胞在肝切除术后内毒素性肝损伤中的作用尚不清楚。我们采用单次给予抗大鼠淋巴细胞血清的淋巴细胞减少（L（-））大鼠、nu/nu无胸腺（T（-））大鼠、从出生起间断注射抗免疫球蛋白（IG）m-链的B细胞消融（B（-））大鼠及其溶剂对照。这些动物接受三分之二肝切除术，随后静脉注射脂多糖（LPS，1.5 mg/kg）。观察各组存活率、血清丙氨酸转氨酶（ALT）、肿瘤坏死因子-α（TNF-α）、IgM水平及总溶血活性（CH_（50））。免疫组化检测IgM或C3在肝组织中的沉积。结果对照组动物24小时存活率为20%，而L（-）、T（-）和B（-）动物的24小时存活率分别为80%、0%和100%。淋巴细胞充足的对照（L（+））和B细胞充足的对照（B（+））动物在攻击后1小时显示血浆TNF-α水平快速升高，随后血浆ALT水平升高。B（+）组注射LPS后4 h血浆IgM水平升高，CH 50活性降低，与注射LPS后0 h比较差异有统计学意义（P < 0. 05）。肝脏组织学显示，LPS给药后4小时出现大量肝坏死，IgM和C3沉积物密集积聚。B细胞消融显著改善血浆ALT、IgM和CH 50水平，显示组织学肝损伤较轻。结论对LPS敏感的B淋巴细胞可能参与肝部分切除术后内毒素诱导的肝损伤的发展。我们的研究结果将发表在Journal of Surgical Research上。