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.

淋巴细胞种群构成了针对内毒素血症的主要防御机制，但尚不清楚肝切开术后B淋巴细胞在内毒素诱导的肝损伤中的作用。我们通过单次给药，通过单次给药，通过抗鼠淋巴细胞，NU/NU allymic（t（ - ））大鼠，通过间歇性注射抗抗 - 免疫球蛋白（IgIg）M-链，从出生和他们的车辆对照组中。这些动物受到三分之二的肝术，随后静脉注射脂多糖（LPS，1.5mg/kg）给药。确定了生存率，血浆丙氨酸转氨酶（ALT），肿瘤坏死剂A（TNF-α）和IgM水平以及总溶血活性（CH50）。通过免疫组织化学评估IgM或C3的肝脏沉积。结果。对照动物的24小时存活率为20％，而L（ - ），T（ - ）和B（ - ）动物的存活率分别为80％，0％和100％。淋巴细胞充足的对照（L（+））和BCELL-FIFIFE对照（B（+））动物在挑战后1小时表现出血浆TNF-A水平的迅速升高，随后血浆ALT水平升高。在B（+）组中，与时间0相比，LPS注射后4小时，血浆IgM水平升高，CH50活性降低。肝组织学相比显着差异。显示出LPS后4小时的IgM和C3沉积物的密集积累，显示出巨大的肝脏坏死。 B细胞消融显着改善了血浆ALT，IgM和CH50水平，显示较少的组织学肝损伤。结论。 B淋巴细胞在部分肝术后内毒素诱导的肝损伤的发展可能暗示。我们的研究结果将发表在手术研究杂志上。