网络首发:2013-03-20,
纸质出版:2013
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环孢霉素A对大鼠心脏移植模型淋巴细胞分子表达与移植心脏病理学改变时相关系的影响[J]. 中山大学学报(医学科学版), 2013,34(2).
Influence of Cyclosporin A on Molecular Expression of Lymphocytes and Relationship with Pathological Changes after Allogenic Heart Transplantation[J]. Journal of Sun Yat-sen University (Medical Sciences), 2013, 34(2).
【目的】 通过环孢素A(CsA)干预的异体异位心脏移植动物模型的研究
对移植术后淋巴细胞分子表达?心肌组织淋巴细胞浸润能力和移植心脏病理改变时相进行比较
探讨环孢素A对其影响?【方法】 SD大鼠为移植心脏供体
Wistar大鼠为移植心脏受体?实验分为心脏移植对照组和环孢素A干预+心脏移植组实验组两组?在移植前及移植后24 h?3 d?7 d?10 d和12 d时间点免疫荧光测定淋巴细胞在心肌组织中浸润能力?实时定量PCR检测淋巴细胞编码基因CD4?CD8 和酪氨酸激酶P59 mRNA表达水平?心肌组织病理学检查判断排斥反应程度?【结果】 ①心脏移植后24 h内
外周血淋巴细胞基因的转录与表达为一过性降低;②心肌组织CD4+?CD8+ 淋巴细胞浸润和Ⅱ级排斥反应病理改变
主要出现于心脏移植后的d3 ~ d7;③环孢素A不能有效抑制移植后3 d内心肌组织CD4+?CD8+淋巴细胞浸润程度的快速增加
但可明显降低移植后d3 ~ d7的心肌组织CD4+ 淋巴细胞的浸润程度;④环孢素A不能完全阻断淋巴细胞P59基因的表达;⑤环孢素A不能有效抑制淋巴细胞CD4基因正调表达
但可抑制CD8基因的转录?【结论】环孢素A的移植排斥反应的抑制作用在大鼠移植后d3 ~ d7?淋巴细胞基因表达?心肌组织淋巴细胞浸润与排斥反应病理改变有关?这将有助于同种移植病人环孢素A的临床应用?
【Objective】 To investigate the effects of cyclosporine A (CsA) on the molecular expression of the lymphocytes and the relationship with the pathological changes after the allogenic heart transplantation. 【Methods】 To use SD rats as the donors and Wistar rats as recipients. The animals were divided into two groups: allogenic heart transplantation Wistar rats with cyclosporine A intervention were used as experimental group and without the cyclosporine A intervention as control group. Before the operation
24 h
72 h
7 d
10 d
and 12d after the transplantation
the lymphocyte infiltrating in myocardial tissues was observed using fluorescence antibodies. CD4
CD8
and P59 mRNA expression level were analyzed by quantified PCR. The histopathological changes in myocardial tissues were monitored to judge the allogenic rejection. 【Results】 (1) 24 h after heart transplantation the transcription and expression of peripheral blood lymphocytes genes were reduced..(2)CD4+
CD8+ lymphcoyte infiltration increased after the transplantation and theⅡdegree rejection pathological changes happened between d3 and d7 after heart transplantation.(3) Cyclosporine A did not affect CD4+ and CD8+ expression and the lymphocytes infiltration in the first 3 days after the transplantation. But CsA significantly reduced the CD4+ infiltration degree in myocardial tissues between d3 and d7. (4) In both groups
CsA was not able to completely block P59 gene expression. (5) Although cyclosporine A did not effectively suppress lymphocyte CD4 gene positive expression but it could suppress CD8 gene transcription. 【Conclusions】 The immunosuppressive effects of CsA was majorly happened in d3~d7 after the allogenic heart transplantation. The peripheral blood lymphocytes genes expression
lymphocytes infiltration in myocardial tissues were correlated with the pathological changes. This finding may provide a better understanding of the clinical use of the CsA for the allogenic heart transplantation patients.
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