Chen Xiao-Gang, Hua Fu, Wang Shou-Guo, Xu Yong-Yi, Yue Hai-Tao, Sun Jin
Department of Orthopedics, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, People's Republic of China,
Department of Gynaecology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, People's Republic of China.
Drug Des Devel Ther. 2018 Aug 1;12:2389-2402. doi: 10.2147/DDDT.S154814. eCollection 2018.
Biosynthesis of leukotriene (LT) by arachidonic acid involves 5-lipoxygenase (5-LO) as an important precursor. Here, we evaluated the role of pseudohypericin (PHP) for its postulated 5-LO inhibitory activity along with a Cys-LT receptor antagonist zafirlukast (ZFL) against inflammatory response and tissue injury in mice.
The spinal injury was induced by two-level laminectomy of T6 and T7 vertebrae. The inflammation was assessed by histology, inflammatory mediators by enzyme-linked immunosorbent assay, apoptosis by Annexin-V, FAS staining, terminal deoxynucleoti-dyltransferase-mediated UTP end labeling (TUNEL) assay and expression of Bax and Bcl-2 by Western blot. Effect on motor recovery of hind limbs was evaluated for 10 days postinjury.
The spinal injury resulted in tissue damage, apoptosis, edema, infiltration of neutrophils with increased expression of tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2). The spinal tissue showed elevated levels of prostaglandin E (PGE2), and LTB and increased phosphorylation of injured extracellular signal-regulated kinase-1/2 (ERK1/2). The PHP, ZFL and combination decreased inflammation, tissue injury and infiltration of neutrophils. Treatment also decreased the levels of PGE, phosphorylation of extracellular signal-regulated kinase-1/2 (pERK 1/2), LT, TNF-α and COX-2 with a marked reduction in apoptosis and improved the motor function.
The present study confirmed 5-LO antagonist activity of PHP and established its neuroprotective role along with ZFL.
花生四烯酸生物合成白三烯（LT）涉及5-脂氧合酶（5-LO）作为重要前体。在此，我们评估了假金丝桃素（PHP）假定的5-LO抑制活性以及半胱氨酰白三烯受体拮抗剂扎鲁司特（ZFL）对小鼠炎症反应和组织损伤的作用。
通过T6和T7椎骨的两级椎板切除术诱导脊髓损伤。通过组织学评估炎症，通过酶联免疫吸附测定法评估炎症介质，通过膜联蛋白-V、FAS染色、末端脱氧核苷酸转移酶介导的UTP末端标记（TUNEL）测定法评估细胞凋亡，并通过蛋白质印迹法评估Bax和Bcl-2的表达。在损伤后10天评估对后肢运动恢复的影响。
脊髓损伤导致组织损伤、细胞凋亡、水肿、中性粒细胞浸润，肿瘤坏死因子-α（TNF-α）和环氧化酶-2（COX-2）表达增加。脊髓组织中前列腺素E（PGE2）、白三烯B（LTB）水平升高，损伤的细胞外信号调节激酶-1/2（ERK1/2）磷酸化增加。PHP、ZFL及其组合减轻了炎症、组织损伤和中性粒细胞浸润。治疗还降低了PGE、细胞外信号调节激酶-1/2（pERK 1/2）、LT、TNF-α和COX-2的水平，显著减少了细胞凋亡并改善了运动功能。
本研究证实了PHP的5-LO拮抗剂活性，并确定了其与ZFL一起的神经保护作用。
