摘要
目的研究重组腺病毒载体在免疫抑制疗法应用中的安全性并探讨环孢素A对该载体在体内清除的影响。方法采取腹膜后注射纯化重组腺病毒建立动物模型,连续给予环孢素A 14 d,取不同时间点大鼠样本,HE染色观察各主要脏器病理反应,免疫组化方法检测肝、脾、肺、肾、肌肉及淋巴结腺病毒的表达情况。结果①HE染色切片,各脏器呈现一过性可逆性轻微炎性反应。②免疫组化检测,对照组中重组腺病毒逐渐减弱至阴性,实验组中重组腺病毒存在时相性明显延长(P<0.05)。③腺病毒分布呈现肝脾肺高表达而其它组织表达相对较低。结论重组腺病毒作为基因治疗载体在免疫抑制疗法应用中具有一定的安全性,环孢素A能够部分抑制实验动物体内的免疫反应从而延长重组腺病毒在体内存在的时间。
Objective To investigate the safety of reconstructed adenovirus in immunosuppressive therapies and to explore the role of ciclosporin A in antagonizing the elimination of the vector. Methods Several rats were retroperitoneally injected with purified ADV-TK in order to make animal models. 14 days after the treatment with ciclosporin A, samples of different periods were taken, and stained with hematoxylin-eosin to detect inflammation reaction, Imm.unohistochemical method was used to examine the expression of adenovirus in organs. Results ①In hematoxylin-eosin stained sections of the organs, some transitory and reversible inflammation was detected. ②In immunohistochemical assay, reconstructed adenovirus decreased gradually with time in the control group, while in the experimental group the adenovirus showed a relative increase as compared with their counterparts （P 〈 0. 05 ）. ③The distribution of adenovirus in liver, spleen and lung were higher than that in other organs. Conclusions Reconstructed adenovirus as a vector is definitely safe when used in immunosuppressive therapy, and ciclosporin A, to some extent, is able to inhibit the immune response of the rats and there by prolong the staying period of adenovirus.
出处
《医学分子生物学杂志》
CAS
CSCD
2006年第3期186-189,共4页
Journal of Medical Molecular Biology
基金
国家重点基础研究发展规划(973计划)(No.2002CB513107)
国家自然科学基金(No.C03020705)~~
关键词
环孢素A
腺病毒
基因治疗载体
免疫抑制疗法
Ciclosporin A
Adenovirus
Gene therapeutic vector
Immunosuppressive therapeutics
