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本研究的目的在于了解利用TPO基因转导降低化学治疗的毒性作用进而增加治疗剂量的可能性。以编码人血小板生成素的真核表达质粒pcDNA3,空载体或生理盐水注射到小鼠体内,3天后给予环磷酰胺,检查动物的血像、精神状态以及大体解剖学改变。结果发现,接受TPO基因转导的小鼠的血小板计数明显高于对照组,未表现出像绝大多数对照鼠那样的脱毛现象,并且耐受了环磷酰胺的二次攻击。对照鼠在接受Cy第一疗程注射后再次攻击,约44％(8/18)的动物死亡。但是,TPO基因转导小鼠的血小板计数在此两周后的攻击之下与对照鼠已无明显差异。病理剖检发现,多数TPO基因转导鼠和未发生脱毛的对照鼠的胸腺体积增大,提示T淋巴细胞参与了对化疗相关的毛发脱落的预防。本研究说明,TPO基因转导能有效地减弱化学治疗的毒性作用。
The purpose of this study is to understand the potential of using TPO gene transduction to reduce the toxic effects of chemotherapy and thereby increase the therapeutic dose. The mice were injected with the eukaryotic expression plasmid pcDNA3 encoding human thrombopoietin, empty vector or saline. After 3 days, cyclophosphamide was given to examine the blood picture, mental status and general anatomical changes of the animals. As a result, it was found that the mice receiving the TPO gene transduction had a significantly higher platelet count than the control group, did not exhibit hair-removal phenomena like most control mice, and were resistant to the second challenge with cyclophosphamide. Control rats challenged again after receiving the first course of Cy injection, and about 44% (8/18) of the animals died. However, platelet counts in TPO-transduced mice did not differ significantly from control mice at this two-week challenge. Pathological examination found that the majority of TPO gene-transduced mice and control mice without shedding of thymus volume, suggesting that T lymphocytes involved in the chemotherapy-related hair loss prevention. This study shows that TPO gene transduction can effectively attenuate the toxic effects of chemotherapy.