Veeravalli Krishna Kumar, Dasari Venkata Ramesh, Tsung Andrew J, Dinh Dzung H, Gujrati Meena, Fassett Dan, Rao Jasti S
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL 61605, USA.
Neurochem Res. 2009 Jul;34(7):1183-94. doi: 10.1007/s11064-008-9894-3. Epub 2009 Jan 17.
We investigated the involvement of tPA after SCI in rats and effect of treatment with human umbilical cord blood derived stem cells. tPA expression and activity were determined in vivo after SCI in rats and in vitro in rat embryonic spinal neurons in response to injury with staurosporine, hydrogen peroxide and glutamate. The activity and/or expression of tPA increased after SCI and reached peak levels on day 21 post-SCI. Notably, the tPA mRNA activity was upregulated by 310-fold compared to controls on day 21 post-SCI. As expected, MBP expression is minimal at the time of peak tPA activity and vice versa. Implantation of hUCB after SCI resulted in the downregulation of elevated tPA activity/expression in vivo in rats as well as in vitro in spinal neurons. Our results demonstrated the involvement of tPA in the secondary pathogenesis after SCI as well as the therapeutic potential of hUCB.
我们研究了大鼠脊髓损伤(SCI)后组织型纤溶酶原激活剂(tPA)的作用以及人脐带血来源干细胞治疗的效果。在大鼠SCI后体内以及体外培养的大鼠胚胎脊髓神经元中,用星形孢菌素、过氧化氢和谷氨酸诱导损伤,测定tPA的表达和活性。SCI后tPA的活性和/或表达增加,并在SCI后第21天达到峰值水平。值得注意的是,在SCI后第21天,tPA mRNA活性相较于对照组上调了310倍。正如预期的那样,在tPA活性峰值时髓鞘碱性蛋白(MBP)表达最低,反之亦然。SCI后植入人脐带血(hUCB)导致大鼠体内以及脊髓神经元体外培养中tPA活性/表达升高的情况下调。我们的结果证明了tPA参与SCI后的继发性发病机制以及hUCB的治疗潜力。