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胸腺内接种供体肝脏特异性抗原可减轻肝脏同种异体移植的排斥反应。

Intrathymic inoculation of donor liver specific antigen alleviates rejection of liver allotransplantation.

作者信息

Jia Chang-Ku, Zheng Shu-Sen, Zhang Ai-Bin

机构信息

Department of Hepatobiliary Pancreatic Surgery, Key Lab of combined Multi Organ Transplantation of Ministry of Public Health, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.

出版信息

J Zhejiang Univ Sci. 2003 Jul-Aug;4(4):485-90. doi: 10.1631/jzus.2003.0485.

Abstract

UNLABELLED

Use and effects of liver specific antigen in orthotopic liver transplantations were researched in this study. Group I: syngeneic control (Wistar-to-Wistar); Group II: acute rejection (SD-to-Wistar); Group III: Thymic inoculation of SD rat LSA day 7 before transplantation. The observation of common situation and survival time, rejection grades, NF-KappaB activity of splenocytes and IL-2mRNA expression of grafted liver were used to analyze acute rejection severity and immune state of animals in different groups. The common situation of group I was very well after transplantation and no signs of rejection were found. Recipients of group II lost body weight progressively. All dead within day 9 to day 13 posttransplantation; median survival time was 10.7+/-0.51 days. It was an optimal acute rejection control. As for group III, 5 out of 6 recipients survived for a long time and common situation was remarkably better than that of group II. Its rejection grades were significantly lower than that of group II(P < 0.05). NF-KappaB activity was only detected in group I at day 5 and day 7 after transplantation, whereas high activity of NF-KappaB was detected at all time points in group II and the low NF-KappaB activity detected in group III was significantly lower than that of group II(P < 0.05). No IL-2mRNA expression was detected at any time point in group I, whereas high level expression was detected at all time points in group II and the low level expression only detected at day 3 in group III was significantly lower than that of group II(P < 0.05).

CONCLUSION

LSA is an important transplantation antigen which is involved directly in the immunorejection of liver transplantation. We report here for the first time that intrathymic inoculation of LSA can alleviate the rejection of liver allotransplantation; and that grafts can survive for a long time thereby, thus leading to a novel way to achieve liver transplantation immunotolerance.

摘要

未标记

本研究探讨了肝特异性抗原在原位肝移植中的应用及效果。第一组:同基因对照(Wistar 大鼠至 Wistar 大鼠);第二组:急性排斥组(SD 大鼠至 Wistar 大鼠);第三组:移植前 7 天胸腺接种 SD 大鼠 LSA。通过观察一般情况、生存时间、排斥反应分级、脾细胞 NF-κB 活性及移植肝 IL-2mRNA 表达,分析不同组动物的急性排斥反应严重程度及免疫状态。第一组移植后一般情况良好,未发现排斥反应迹象。第二组受体体重逐渐减轻,均在移植后第 9 天至第 13 天内死亡,中位生存时间为 10.7±0.51 天,为典型的急性排斥反应对照。第三组 6 只受体中有 5 只长期存活,一般情况明显优于第二组,排斥反应分级显著低于第二组(P<0.05)。NF-κB 活性仅在移植后第 5 天和第 7 天在第一组中检测到,而第二组在所有时间点均检测到高活性的 NF-κB,第三组检测到的低 NF-κB 活性显著低于第二组(P<0.05)。第一组在任何时间点均未检测到 IL-2mRNA 表达,而第二组在所有时间点均检测到高水平表达,第三组仅在第 3 天检测到低水平表达,且显著低于第二组(P<0.05)。

结论

LSA 是一种重要的移植抗原,直接参与肝移植的免疫排斥反应。我们首次报道胸腺内接种 LSA 可减轻肝同种异体移植的排斥反应,使移植物长期存活,从而为实现肝移植免疫耐受开辟了一条新途径。

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