抑制实验性感染细粒棘球蚴大鼠原位肝移植后急性排斥反应。
Suppression of acute rejective response following orthotopic liver transplantation in experimental rats infected with Echinococcus multilocularis.
机构信息
State Key Lab Breeding of Xinjiang Major Disease Research, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China.
出版信息
Chin Med J (Engl). 2011 Sep;124(18):2818-23.
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.
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）可能是治疗终末期肝泡型包虫病的唯一有效方法。然而，在一些 AE 患者中，OLT 后不能完全消除肝外 Em。我们旨在研究 Em 逃避引起的免疫变化是否会影响排斥反应。
方法
通过向布朗-挪威（BN）大鼠腹部注射 Em 悬浮液建立 AE 大鼠模型。三个月后，在实验组，Lewis（LEW）大鼠的肝脏移植到 Em 感染的 BN 大鼠。在对照组中，移植来自 LEW 大鼠到健康的 BN 大鼠。OLT 后第 1、3、5 和 7 天采集肝组织和外周血（PB）样本。苏木精和伊红（H&E）染色后分析肝组织；流式细胞术检测外周血细胞中 CD4、CD8 和 CD28 的数量；逆转录 PCR（RT-PCR）检测趋化因子 fractalkine（Fkn）的表达。酶联免疫吸附试验（ELISA）检测血清中白细胞介素 10（IL-10）的含量。在每组中，保留 8 只 BN 大鼠观察存活时间。
结果
实验组受体的存活时间较对照组延长。实验组排斥反应发生较晚，程度较轻。实验组 CD4、CD8、CD28 T 细胞比例及 Fkn mRNA 表达较低，而实验组血清 IL-10 水平较对照组升高。
结论
Em 感染大鼠 OLT 后急性排斥反应减弱，受体存活时间延长。Em 通过升高 IL-10 分泌、减少效应 T 细胞、抑制 Fkn 表达，从而减少炎症细胞浸润肝脏，在这一过程中发挥作用。
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