中文摘要：

目的检测经不同途径移植骨髓间充质干细胞后大鼠脑梗死模型中131I一氟一碘阿糖呋喃基尿嘧啶（FIAU）的生物分布及脑组织中胸苷激酶（TK）基因的表达，为核素报告基因显像无创性监测细胞移植治疗脑梗死提供实验依据。方法制备携带TK一内部核糖体连接位点一脑源性神经生长因子（IRES—BDNF）基因的腺病毒重组体Ad5一TK—IRES—BDNF一增强型绿色荧光蛋白（EGFP）；线栓法制作大鼠脑梗死模型；将转基因的干细胞分别通过脑实质、侧脑室、颈动脉和尾静脉注射人大鼠脑梗死模型中，以正常大鼠为对照组；Iodogen固相氧化法标记氟·阿糖呋喃基尿嘧啶（FAU）后进行生物分布研究，计算％ID／g；采用实时定量PCR和Westernblot定量分析TK基因的表达；数据分析采用独立样本t检验、单因素方差分析及Pearson相关分析。结果原位移植组梗死侧脑组织中的％ID／g为0．124±0．013，明显高于侧脑室移植组（0．052±0．004）、颈动脉移植组（0．061±0．002）、尾静脉移植组（0．059±0．005）和对照组（0．005±0．001），差异有统计学意义（t=2．913～5．652，P均〈0．05），其他移植细胞组组间差异无统计学意义（￡=0．694—1．448，P均〉0．05）。所有移植细胞组内两侧脑组织％ID／g的差异有统计学意义（f=9．004～15．734，P均〈0．05），而对照组两侧间差异无统计学意义（t=1．511，P=0．182）。此外，原位移植组梗死侧脑组织中TK基因的表达高于其他各组，差异有统计学意义（t=7．482～12．371，P均〈0．05）；且脑组织TK基因表达的相对量与％ID／g呈正相关（r=0．971，P〈0．001）；脑组织内TK／[3一actin的比值与％ID／g呈正相关（r=0．899，P：0．002）。结论原位注射是治疗脑梗死的最佳细胞移植途径；选择适当示踪剂，可利用PET或SPECT进行无创性活体监测细胞移植治疗脑梗死?

英文摘要：

Objective To study the biodistribution of 131 I-2＇-deoxy-l-[3-D-arabinofuranosyl-5-iodo- uracil （FIAU） in the rat middle cerebral artery occlusion model and the expression of thymidine kinase （TK） gene in brain tissue after gene-modified stem cell transplantation, and thus evaluate the possibility of further noninvasive monitoring of stem cell transplantation therapy in cerebral infarction. Methods Adeno- virus recombinant Ad5-TK-internal ribosome entry site-brain derived heurotrophic factor-enhanced green flo- recent protein（IRES-BDNF-EGFP） carrying TK-IRES-BDNF gene was prepared. Cerebral infarction model was established in rats by intraluminal middle cerebral artery occlusion with nylon monofilament. Gene mod- ified bone marrow mesenchymal stem cells were transplanted via intraparenchymal route, lateral ventricle, carotid artery and tail vein, respectively. The normal rats were used as controls. ,31 I- FAU was prepared to be the tracer for biodistribution study and the % ID/g was calculated based on measurement of the tissue ra- dioactivity counts. The expression of TK gene was evaluated by quantitative real-time PCR （QR-PCR） and Western blot analysis. Data were analyzed with independent-samples t-test, one-way analysis of variance （ANOVA） test, and Pearson linear correlation test. Results The % ID/g of infarcted brain tissue in the intraparenchymal group was 0. 124 ± 0. 013, which was significantly higher than that in lateral ventriclegroup （0.052 ± 0. 004 ）, carotid artery group （0.061 ± 0. 002）, tail vein group （0. 059 ± 0. 005 ） and control group （0. 005 -± 0. 001 ） （ t = 2. 913 - 5. 652, all P 〈 0.05 ）, while there were no statistically signifi- cant differences among the other route transplanted groups （ t = 0. 694 - 1. 448, all P 〉 0.05 ）. The differences of % ID/g between the infarcted and contralateral sides of brain tissue in all transplanted groups were statistically significant （ t = 9. 004 - 15. 734, all P 〈 0.05 ）, while there was no st