Research on Apoptosis during Cardiac Xenograft Rejection

心脏异种移植排斥过程中细胞凋亡的研究

• 批准号: 10671237
• 负责人: OHMI Mikio
• 金额: $ 1.09万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671237/
• 关键词: Cardiac transplantation; Xenotransplantation; Apoptosis; 心臓移植

[Aim] To clarify the relationship between cardiac xenograft rejection and apoptosis using experimental heart transplantation model (Hamster to Rat)[Method] Experimental cardiac Xenotransplantation was performed using Hamster as the heart donor and Lewis rat as the recipient with the modified method described by Ono and Lindsey. Transplanted heart were examined in 0, 4, 8, 24 and 48 hours after transplantation.[Results] Mean survival days for the transplanted xenograft was 3 days. Hematoxylin-eosin staining of the myocardium revealed no particular change during 4-8 hours after Tx, and neutrophylic cell infiltration around vessels after 24 hours. Focal infiltration of the neutropils was observed in the epicardium and endocardium after 48 hours. Myocardial necrosis was observed after 48 hours. No vasculitis was observed after 48 hours. Lymphocyte infiltration was not obvious during all rejection process. TUNEL staining revealed positive cell nucleus of endocardium and vascular endothel during 4 to 48 hours after Tx. Fas positive cells were observed in the endocardium and vascular endothelium during 4 to 8 hours after Tx.[Conclusions] Neutrophilic cells are main infiltration cells during concordant cardiac xenograft rejection, which is different with allograft rejection with lymphocyte infiltration. Fas associated apoptosis was in process on the endocardium and vascular endothelium before morphological rejection, which suggests suppression of apoptosis might lead to concordant cardiac xenograft rejection.

[Aim][方法]采用Ono和Lindsey改良的方法，以Wistar大鼠为供体，刘易斯大鼠为受体，进行异种心脏移植。分别于移植后0、4、8、24、48 h进行心脏检查。[结果]移植瘤平均存活时间为3d。心肌的苏木精-伊红染色显示在Tx后4-8小时内没有特别的变化，并且在24小时后在血管周围有中性细胞浸润。48小时后，在心外膜和心内膜中观察到中性粒细胞的局灶性浸润。48小时后观察到心肌坏死。48小时后未观察到血管炎。排斥反应过程中淋巴细胞浸润不明显。TUNEL染色显示，Tx后4 ~ 48 h内，内皮细胞和血管内皮细胞核呈阳性反应。Tx后4 ~ 8h，Fas阳性细胞出现于内皮细胞和血管内皮细胞。[结论]中性细胞是异种心脏一致性排斥反应中的主要浸润细胞，这与淋巴细胞浸润的同种异体排斥反应不同。在形态学排斥反应发生之前，Fas相关的凋亡在内皮细胞和血管内皮细胞上进行，这表明抑制凋亡可能导致一致性异种心脏移植排斥反应。