Department of Molecular Biology, Capital Medical University Affiliated with Beijing Anzhen Hospital, Beijing Institute of Heart, Lung & Blood Vessel Diseases, Beijing 100029, PR China.
Transpl Immunol. 2013 Dec;29(1-4):82-7. doi: 10.1016/j.trim.2013.06.002. Epub 2013 Jul 10.
To systematically compare the expression of coding genes with pathological changes of transplanted cardiac tissue and peripheral blood lymphocytes in an allo-heterotopic rat cardiac transplant model. Using SD rats as donors and Wistar rats as recipients, animals were divided into two groups, control and cyclosporine A intervention plus heart transplant groups. After transplant at 1, 3, 7, 10 and 12d, we assessed the ability of lymphocytes to infiltrate into cardiac tissues and levels of leukocyte coding genes in peripheral blood. Histopathological changes were monitored in cardiac tissue to determine the level of transplant rejection.
(1) 24h after transplant peripheral blood lymphocytes' transcription and expression were temporarily reduced. (2) CD4(+) and CD8(+) lymphocytes infiltrate into cardiac tissue and Grade 1R pathological changes were observed 3d-7d after heart transplant. (3)Cyclosporine A was not able to completely block heart transplant rejection.(4) Although cyclosporine A was not able to effectively suppress CD4(+) T cell gene expression, it did suppress CD8(+) T cell gene transcription. (5) Cyclosporine A did not effectively reduce the rapid infiltration of CD4(+) or CD8(+) infiltration in 3d, but significantly reduced the degree of CD4(+) T cell infiltration in cardiac tissues between 3 and 7d. (6) Differential display (DD-PCR): Graft control group: there were differences in 2,3-bisphosphoglycerate, ribosomal protein S25, 12S ribosomal, gig18, MHC-III and ATPase H(+), which occurred 24h before CD4/CD8 surface protein expression. Cyclosporine A group: there were differences in thrombospondin-1, TCR, 2,3-bisphosphoglycerate, sodium channel beta-1, gig18 and TCR. In the cyclosporine A group 2,3-bisphosphoglycerate positive expression was observed 24h after the control group, which indicates that cyclosporine A slowed down the 2,3-bisphosphoglycerate transcription rate in peripheral lymphocytes and delayed its expression time. Cyclosporine A also suppressed gig18 transcription in peripheral lymphocytes. After 24h, sodium channel beta-1 was positively expressed in the cyclosporine A group. The relationship between molecular surface receptor expression and coding genes in cardiac tissue and peripheral blood after transplant indicates that early detection of acute rejection and anti-rejection drugs' curative effect can be assessed.
系统比较同种异体异位大鼠心脏移植模型中移植心脏组织和外周血淋巴细胞的编码基因表达与病理变化。使用 SD 大鼠作为供体，Wistar 大鼠作为受体，将动物分为对照组和环孢素 A 干预加心脏移植组。移植后 1、3、7、10 和 12d 时，评估淋巴细胞浸润心脏组织的能力和外周血白细胞编码基因的水平。监测心脏组织的组织病理学变化以确定移植排斥反应的程度。
（1）移植后 24h 外周血淋巴细胞转录和表达暂时降低。（2）CD4(+)和 CD8(+)淋巴细胞浸润心脏组织，心脏移植后 3-7d 观察到 1R 级病理变化。（3）环孢素 A 不能完全阻断心脏移植排斥反应。（4）虽然环孢素 A 不能有效抑制 CD4(+)T 细胞基因表达，但它确实抑制了 CD8(+)T 细胞基因转录。（5）环孢素 A 不能有效抑制 3d 时 CD4(+)或 CD8(+)的快速浸润，但在 3-7d 时显著降低 CD4(+)T 细胞在心脏组织中的浸润程度。（6）差异显示（DD-PCR）：移植物对照组：在 CD4/CD8 表面蛋白表达前 24h，2,3-二磷酸甘油酸、核糖体蛋白 S25、12S 核糖体、gig18、MHC-III 和 ATPase H(+)存在差异。环孢素 A 组：血小板反应蛋白-1、TCR、2,3-二磷酸甘油酸、钠通道β-1、gig18 和 TCR 存在差异。在环孢素 A 组中，24h 后观察到 2,3-二磷酸甘油酸阳性表达，这表明环孢素 A 降低了外周淋巴细胞中 2,3-二磷酸甘油酸的转录率，并延迟了其表达时间。环孢素 A 还抑制了外周淋巴细胞中 gig18 的转录。24h 后，环孢素 A 组钠通道β-1 呈阳性表达。移植后心脏组织和外周血中分子表面受体表达与编码基因的关系表明，可以评估急性排斥反应的早期检测和抗排斥药物的疗效。
