Cho Young Sam, Kim Su Jin, Kim Khae Hawn
Department of Urology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Department of Urology, Yonsei University Wonju College of Medicine, Wonju, Korea.
Int Neurourol J. 2020 Nov;24(Suppl 2):104-110. doi: 10.5213/inj.2040448.224. Epub 2020 Nov 23.
Neurogenic bladder (NB) associated with spinal cord injury (SCI) is a serious health problem. However, no effective treatment has been developed for SCI patients with NB. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitors have been proposed as a promising option for inducing neural regeneration. Therefore, we investigated the effects of a tissue gene nerve (TGN), PTEN inhibitor, on voiding function, motor function, and the expression of growth factors after SCI.
In this experiment, female rats were randomly divided into 3 groups (n=10 in each group): the sham-operation group, the SCI-induced group, and the SCI-induced and TGN-treated group. Cystometry; the Basso, Beattie, and Bresnahan (BBB) scale test; the ladder walking test; hematoxylin and eosin staining; and Western blotting for brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF) were performed to evaluate functional and molecular changes.
After SCI, the rats exhibited decreased walking ability according to the BBB scale test and impaired coordinative function according to the ladder walking test. The PTEN inhibitor promoted enhanced walking ability and coordinative function. Cystometry showed voiding impairment after SCI and improved voiding function was observed after PTEN treatment. Overexpression of VEGF, BDNF, and NGF were observed after SCI. Administration of PTEN inhibitors significantly attenuated the overexpression of growth factors due to SCI.
PTEN inhibitor treatment diminished the overexpression of growth factors and promoted the repair of damaged tissue. PTEN inhibitor-treated rats also showed improved motor function and improved voiding function. Therefore, we suggest TGN as a new therapeutic agent that can be applied after SCI.
与脊髓损伤（SCI）相关的神经源性膀胱（NB）是一个严重的健康问题。然而，尚未开发出针对患有NB的SCI患者的有效治疗方法。10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）抑制剂已被提议作为诱导神经再生的一种有前景的选择。因此，我们研究了组织基因神经（TGN），一种PTEN抑制剂，对SCI后排尿功能、运动功能和生长因子表达的影响。
在本实验中，将雌性大鼠随机分为3组（每组n = 10）：假手术组、SCI诱导组和SCI诱导并TGN治疗组。进行膀胱测压；Basso、Beattie和Bresnahan（BBB）量表测试；阶梯行走测试；苏木精和伊红染色；以及针对脑源性神经营养因子（BDNF）、血管内皮生长因子（VEGF）和神经生长因子（NGF）的蛋白质免疫印迹法，以评估功能和分子变化。
SCI后，根据BBB量表测试，大鼠行走能力下降，根据阶梯行走测试，其协调功能受损。PTEN抑制剂促进了行走能力和协调功能的增强。膀胱测压显示SCI后存在排尿障碍，PTEN治疗后观察到排尿功能改善。SCI后观察到VEGF、BDNF和NGF的过表达。给予PTEN抑制剂显著减弱了SCI导致的生长因子过表达。
PTEN抑制剂治疗减少了生长因子的过表达并促进了受损组织的修复。接受PTEN抑制剂治疗的大鼠还表现出运动功能改善和排尿功能改善。因此，我们建议将TGN作为一种可在SCI后应用的新治疗药物。
