Effect of Emodin in Suppressing Acute Rejection Following Liver Allograft Transplantation in Rats

Effect of Emodin in Suppressing Acute Rejection Following Liver Allograft Transplantation in Rats
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大黄素抑制大鼠同种异体肝移植后急性排斥反应的作用

DOI:
10.1007/s11655-010-0151-7
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发表时间:
2010-04-10
影响因子:
2.9
通讯作者:
Zheng Shu-sen
Zheng Shu-sen
中科院分区:
医学3区
文献类型:
--
作者:
Lin Sheng-zhang;Tong Hong-fei;Zheng Shu-sen

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Objective.探讨大黄素抑制大鼠肝移植急性排斥反应的作用机制。研究方法:将Brown Norway(BW)大鼠原位肝移植(奥尔特)受体分为3组,A组为同种异体移植(BW大鼠为供体),B组为同种异体移植(刘易斯大鼠为供体),C组为同种异体移植加大黄素治疗(50 mg/kg/d)。移植后第7天处死动物,检测肝组织学、血浆细胞因子水平和T细胞亚群表达。结果如下:与A组相比,B组大鼠出现严重的排斥反应,排斥反应活性指数(RAI)为7.67 ± 0.98,肝细胞广泛凋亡,凋亡指数(AI)为35.83 ± 2.32,血浆白细胞介素2(IL-2)、白细胞介素10(IL-10)、肿瘤坏死因子α(TNF-α)水平升高(TNF-α)、CD 4(+)和CD 4(+)/CD 8(+)比率。与同种异体移植组相比,C组的排斥反应和肝细胞凋亡程度降低,血浆IL-2、TNF-α、CD 4(+)和CD 4(+)/CD 8(+)比值降低,但IL-10水平升高。结论:大黄素可减轻肝移植术后急性排斥反应,其作用机制可能与保护肝细胞免于凋亡、使Th 1范式向Th 2极化、抑制血浆中CD 4(+)T细胞增殖有关。
Objective. To investigate the mechanism of action of emodin for suppressing acute allograft rejection in a rat model of liver transplantation. Methods: Brown Norway (BW) recipient rats of orthotopic liver transplantation (OLT) were divided into three groups, Group A receiving isografting (with BW rats as donor), Group B receiving allografting (with Lewis rats as donor), Group C receiving allografting and emodin treatment (50 mg/kg daily). They were sacrificed on day 7 of post-transplantation, and their hepatic histology, plasma cytokine levels, and T-cell subset expression were detected. Results: Compared with those in Group A, rats in Group B exhibited severe allograft rejection with a rejection activity index (RAI) of 7.67 +/- 0.98, extensive hepatocellular apoptosis with an apoptosis index (AI) of 35.83 +/- 2.32, and elevated plasma levels of interleukin-2 (IL-2), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), CD4(+) and CD4(+)/CD8(+) ratio. However, recipients in Group C showed a decrease in histological grade of rejection and hepatocellular apoptosis, as well as a decrease in plasma levels of IL-2, TNF-alpha, CD4(+) and CD4(+)/CD8(+) ratio, but elevated levels of IL-10 as compared with the allograft group. Conclusion: Post-OLT acute rejection could be attenuated by emodin, its mechanism of action may be associated with protecting hepatocytes from apoptosis, polarizing the Th 1 paradigm to Th2, and inhibiting the proliferation of CD4(+) T cell in plasma.