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

淋巴细胞群是抵抗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引起的肝损伤中的作用尚不清楚。我们采用淋巴细胞减少（L(-)）大鼠单次给药抗大鼠淋巴细胞血清，nu/nu胸腺增生（T(-)）大鼠，B细胞消融（B(-)）大鼠，从出生开始间歇性注射抗免疫球蛋白（Ig） m链，以及它们的对照。这些动物接受三分之二肝切除术，随后静脉注射脂多糖（LPS, 1.5mg/kg）。测定大鼠存活率、血浆丙氨酸转氨酶（ALT）、肿瘤坏死因子-a （TNF-α）、IgM水平及总溶血活性（CH50）。免疫组织化学检测IgM或C3的肝组织沉积。结果。对照动物24小时存活率为20%，L（-）、T（-）和B（-）动物24小时存活率分别为80%、0%和100%。淋巴细胞充足对照组（L(+)）和B细胞充足对照组（B(+)）动物在刺激1小时后血浆TNF-a水平迅速升高，随后血浆ALT水平升高。B（+）组大鼠注射LPS后4小时血浆IgM水平升高，CH50活性降低，与0小时比较差异有统计学意义。肝脏组织学显示，LPS给药后4小时出现大量肝坏死，伴有IgM和C3沉积物的密集积累。B细胞消融可显著改善血浆ALT、IgM和CH50水平，减少肝组织损伤。结论。对LPS敏感的B淋巴细胞可能与肝部分切除术后内毒素诱导的肝损伤的发展有关。我们的研究结果将发表在《外科研究杂志》上。

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.