Department of Anatomy, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait.
Naunyn Schmiedebergs Arch Pharmacol. 2012 Aug;385(8):807-22. doi: 10.1007/s00210-012-0758-7. Epub 2012 May 11.
Muscle degeneration and impairment following nerve injury could lead to apoptosis as a result of increased levels of reactive oxygen species. This activates the apoptotic cascade through mitochondrial dysfunction and damage to lipids, proteins, and DNA. In considering of the multifactorial protective properties of green tea polyphenols (-)-epigallocatechin-3-gallate (EGCG), this study investigates whether EGCG treatment does improve skeletal muscle function impairments, induced by crushing of the sciatic nerve. Compared to the saline-treated injured group of animals, EGCG treatment of axonotomized animals showed significant motor enhancement in the toe spread and foot positioning analysis and gain in the percentage motor deficit. The proprioceptive function expressed by the hopping response showed significant progression in the EGCG-treated group. Recovery of sensory innervation was followed by a slowly retreating neuropathic pain-like syndrome in the EGCG-treated animals. Muscle tissues from injured limb showed severe histopathological alterations that were significantly attenuated by EGCG treatment at the end of week 3 post-surgery. Semi-quantitative desmin immunohistochemistry revealed intense staining in the saline-treated injured animals, whereas EGCG treatment decreased the desmin immunoreactivity back to sham control levels. Using RT-PCR, EGCG treatment induced a significant anti-apoptotic effect in injured muscle tissues by normalizing the Bax/Bcl-2 ratio back to baseline levels and inhibiting overexpression of the p53 apoptotic gene at days 3 and 7 post-surgery. In conclusion, our results demonstrate that EGCG enhances functional recovery, protects muscle fibers from cellular death by activating anti-apoptotic signaling pathway, and improves morphological recovery in skeletal muscle after nerve injuries.
神经损伤后肌肉退化和功能障碍可导致活性氧水平升高引起的细胞凋亡。这会通过线粒体功能障碍和脂质、蛋白质和 DNA 的损伤激活凋亡级联。考虑到绿茶多酚 (-)-表没食子儿茶素-3-没食子酸酯 (EGCG) 的多种保护特性,本研究调查了 EGCG 治疗是否可以改善坐骨神经挤压引起的骨骼肌功能障碍。与接受盐水治疗的损伤动物组相比,EGCG 治疗的轴索切断动物在趾间距和足部定位分析中表现出明显的运动增强,并且运动缺陷百分比增加。EGCG 治疗组的本体感受功能表现出明显的进展。感觉神经支配的恢复后,EGCG 治疗动物出现了缓慢消退的神经病理性疼痛样综合征。受伤肢体的肌肉组织显示出严重的组织病理学改变,这些改变在手术后第 3 周接受 EGCG 治疗后明显减轻。半定量结蛋白免疫组化显示,接受盐水治疗的损伤动物中染色强烈,而 EGCG 治疗则将结蛋白免疫反应性降低至假手术对照水平。通过 RT-PCR,EGCG 治疗通过将 Bax/Bcl-2 比值恢复到基线水平并抑制手术后第 3 天和第 7 天 p53 凋亡基因的过度表达,在受伤肌肉组织中诱导了显著的抗凋亡作用。总之,我们的结果表明,EGCG 通过激活抗凋亡信号通路增强功能恢复,保护肌肉纤维免受细胞死亡,并改善神经损伤后骨骼肌的形态恢复。