Suppression of acute rejective response following orthotopic liver transplantation in experimental rats infected with Echinococcus multilocularis
Suppression of acute rejective response following orthotopic liver transplantation in experimental rats infected with Echinococcus multilocularis
复制标题
多房棘球绦虫感染实验大鼠原位肝移植后急性排斥反应的抑制
DOI：
10.3760/cma.j.issn.0366-6999.2011.18.004
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发表时间：
2011-09-20
影响因子：
6.1
通讯作者：
Wen Hao
中科院分区：
文献类型：
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作者：
Li Tao;Zhao Jin-ming;Wen Hao
背景 肝泡型包虫病（AE）是一种人类寄生虫病，由多房棘球绦虫（Em）引起。原位肝移植（OLT）可能是终末期肝脏AE的唯一有效治疗方法。然而，在一些AE患者中，OLT后肝外Em不能完全消除。我们的目的是研究Em逃避引起的免疫学变化是否会影响排斥反应。方法通过将Em悬浮液注射到棕色挪威(BN)大鼠的腹部建立AE大鼠模型。三个月后，实验组将Lewis (LEW)大鼠的肝脏移植到Em感染的BN大鼠体内。在对照组中，移植是从 LEW 大鼠到健康 BN 大鼠。 OLT 后第 1、3、5 和 7 天收集肝组织和外周血 (PB) 样本。苏木精和伊红 (H&E) 染色后对肝组织进行分析；流式细胞术检测外周血细胞CD4、CD8、CD28的数量。通过逆转录PCR（RT-PCR）检测趋化因子fractalkine（Fkn）的表达。通过酶联免疫吸附测定 (ELISA) 测定血清中的白细胞介素 10 (IL-10)。每组留8只BN大鼠观察存活时间。结果实验组受者存活时间较对照组延长。实验组的排斥反应发生较晚且较温和。实验组CD4、CD8、CD28 T细胞百分比和Fkn mRNA表达较低。而实验组血清IL-10水平高于对照组。结论Em感染大鼠OLT后急性排斥反应减弱，受者生存时间延长。 Em可能在此过程中通过提高IL-10分泌、减少效应T细胞、抑制Fkn的表达，从而减少炎症细胞向肝脏的浸润而发挥作用。中医杂志 2011;124(18):2818-2823
Background Hepatic alveolar echinococcosis (AE) is a parasitic disease in humans and caused by the Echinococcus multilocularis (Em). Orthotopic liver transplantation (OLT) may be the only effective treatment for end-stage hepatic AE. However, in some AE patients, extrahepatic Em can not be completely eliminated after OLT. We aimed to study whether the immunological changes caused by Em evasion may influence the rejective response.Methods Rat modles of AE were established by injecting the Em suspension into abdomen of Brown Norway (BN) rats. Three months later, in the experimental group, the liver was transplanted from Lewis (LEW) rats to Em-infected BN rats. In the control group, transplantation was from LEW rats to healthy BN rats. Liver tissue and peripheral blood (PB) samples were collected on days 1, 3, 5, and 7 after OLT. Liver tissue was analyzed after hematoxylin and eosin (H&E) staining; numbers of CD4, CD8, and CD28 on peripheral blood cells were detected by flow cytometry; and expression of the chemokine fractalkine (Fkn) was detected by reverse transcription PCR (RT-PCR). Interleukin-10 (IL-10) was measured in the serum by enzyme-linked immunosorbent assay (ELISA). In every group, eight BN rats were retained for observing survival time.Results The survival times of recipients in the experimental group were prolonged compared with those in the control group. The rejective response occurred later and was milder in the experimental group. percentage of CD4, CD8, CD28 T-cells and Fkn mRNA expression were lower in the experimental group. While the serum IL-10 levels were higher in the experimental group than those in the control group.Conclusions Acute rejective response after OLT was attenuated in the rats with Em infection, and the recipients' survival time was prolonged. Em may play a role in this process by elevating IL-10 secretion, decreasing the effector T cells, inhibiting the expression of Fkn, which lead to reduce the inflammatory cells infiltration into the liver. Chin Med J 2011;124(18):2818-2823