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目的 探讨带有ＨＳＶｔｋ 基因的重组腺病毒（Ａｄ．ｔｋ） 结合ＧＣＶ 对国人脑胶质瘤ＳＨＧ４４ 的治疗作用。方法 Ｘｇａｌ 染色比较带有报告基因ＬａｃＺ的重组腺病毒（Ａｄ．ＬａｃＺ） 转染ＳＨＧ４４ 细胞和大鼠脑胶质瘤Ｃ６ 细胞的效率，ＭＴＴ法比较Ａｄ．ｔｋ／ＧＣＶ 系统对ＳＨＧ４４ 和Ｃ６ 细胞的敏感性，ＤＮＡ片段分析细胞杀伤机制；在活体用Ａｄ．ｔｋ／ＧＣＶ 治疗ＳＨＧ４４ 移植瘤。结果 ＭＯＩ为５０ 时，Ａｄ．ＬａｃＺ感染ＳＨＧ４４ 细胞的效率近１００％ ，较Ｃ６ 细胞高；ＭＯＩ为１００ 时，Ａｄ．ｔｋ 感染的ＳＨＧ４４ 细胞对ＧＣＶ 的敏感性较Ｃ６ 细胞高，其半致死剂量（ＩＣ５０） 分别为０ ．１２ μｍｏｌ／Ｌ 和０ ．２６ μｍｏｌ／Ｌ，有凋亡机制参与其细胞杀伤；５ ×１０８ＰＦＵ 的Ａｄ．ｔｋ 肿瘤原位注射结合ＧＣＶ治疗，有效抑制ＳＨＧ４４ 移植瘤生长，肿瘤组织坏死，出血伴有纤维组织增生；与Ａｄ ．ｔｋ／ＰＢＳ组、Ａｄ．ＬａｃＺ／ＧＣＶ 组、ＰＢＳ组相比，肿瘤抑制效率分别为９２．５ ％ 、９２．６％ 、８９ ．５％ （ Ｐ＜０ ．０１） 。结论 Ａｄ．ｔｋ／ＧＣＶ系统对人脑胶质瘤细胞的感染效率和敏感性较高，治疗国人脑胶质瘤效果显著。
Objective To investigate the therapeutic effect of recombinant adenovirus carrying HSV tk gene (Ad.tk) and GCV on human glioma SHG44. Methods Xgal staining compared with the reporter gene LacZ recombinant adenovirus (Ad.LacZ) transfected SHG44 cells and rat C6 glioma cell efficiency, MTT method compared Ad. Sensitivity of tk / GCV system to SHG44 and C6 cells, DNA fragmentation analysis of cell killing mechanism; Ad. tk / GCV treatment of SHG44 xenografts. Results MOI of 50, Ad. The efficiency of LacZ infection in SHG44 cells was nearly 100% higher than that in C6 cells. When MOI was 100, Ad. The SHK44 cells infected with tk were more sensitive to GCV than C6 cells with a median lethal dose (IC50) of 0. 12 μmol / L and 0. 26 μmol / L, with apoptosis mechanism involved in their cell killing; 5 × 108PFU Ad. tk tumor in situ injection combined with GCV treatment, effectively inhibit the growth of SHG44 xenograft, tumor necrosis, hemorrhage associated with fibrosis; and Ad. tk / PBS group, Ad. The tumor inhibition efficiencies of LacZ / GCV group and PBS group were 92.5%, 92.6%, 89 respectively. 5% (P <0 .01). Conclusion. tk / GCV system of human glioma cells infected with high efficiency and sensitivity, the treatment of human glioma significant effect.