Li Meng, Gao Weiman, Ji Le, Li Jia, Jiang Wanting, Ji Wenchen
Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiaotong University, 710061, China.
Department of Orthopedics, Shaanxi Provincial People's Hospital, 710068, China.
Biomed Res Int. 2020 Dec 17;2020:3852450. doi: 10.1155/2020/3852450. eCollection 2020.
Methane saline (MS) can be used to treat many diseases via its anti-inflammatory, antiapoptotic, and antioxidative activities. However, to date, there is no published evidence as to whether MS has any effect on traumatic brain injury (TBI). The Wnt signalling pathway regulates cell proliferation, differentiation, migration, and apoptosis; however, whether the Wnt signalling pathway regulates any effect of MS on TBI is unknown. This study was designed to explore the role of MS in the treatment of TBI and whether the Wnt pathway is involved.
Sprague-Dawley rats were randomly divided into five groups: sham, TBI, TBI+10 ml/kg MS, TBI+20 ml/kg MS, and TBI+30 ml/kg MS. After induction of TBI, MS was injected intraperitoneally once daily for seven consecutive days. Neurological function was evaluated by the Neurological Severity Score (NSS) at 1, 7, and 14 days after TBI. Haematoxylin-eosin (HE) staining, inflammatory factors, neuron-specific enolase (NSE) staining, oxidative stress, and cell apoptosis were measured and compared 14 d after TBI to identify the optimal dose of MS and to investigate the effect of MS on TBI. In the second experiment, Sprague-Dawley rats were randomly divided into four groups: sham, TBI, TBI+20 ml/kg MS, and TBI+20 ml/kg MS+Dickkopf-1 (DKK-1, a specific inhibitor of the Wnt pathway). NSE, caspase-3, superoxide dismutase (SOD), Wnt3a, and -catenin were detected by real-time PCR and Western blotting. The results from each group were compared 14 d after TBI to determine the regulatory role of the Wnt pathway.
Methane saline significantly inhibited inflammation, oxidative stress, and cell apoptosis, thus protecting neurons within 14 days of TBI. The best treatment effect against TBI was obtained with 20 ml/kg MS. When the Wnt pathway was inhibited, the treatment effect of MS was impaired.
Methane saline ameliorates TBI through its anti-inflammatory, antiapoptotic, and antioxidative effects via activation of the Wnt signalling pathway, which plays a part but is not the only mechanism underlying the effects of MS. Thus, MS may be a novel strategy for treating TBI.
甲烷生理盐水(MS)可通过其抗炎、抗凋亡和抗氧化活性用于治疗多种疾病。然而,迄今为止,尚无关于MS对创伤性脑损伤(TBI)是否有任何作用的公开证据。Wnt信号通路调节细胞增殖、分化、迁移和凋亡;然而,Wnt信号通路是否调节MS对TBI的任何作用尚不清楚。本研究旨在探讨MS在TBI治疗中的作用以及Wnt通路是否参与其中。
将Sprague-Dawley大鼠随机分为五组:假手术组、TBI组、TBI + 10 ml/kg MS组、TBI + 20 ml/kg MS组和TBI + 30 ml/kg MS组。诱导TBI后,连续7天每天腹腔注射MS。在TBI后1、7和14天通过神经严重程度评分(NSS)评估神经功能。在TBI后14天测量并比较苏木精-伊红(HE)染色、炎症因子、神经元特异性烯醇化酶(NSE)染色、氧化应激和细胞凋亡,以确定MS的最佳剂量并研究MS对TBI的影响。在第二个实验中,将Sprague-Dawley大鼠随机分为四组:假手术组、TBI组、TBI + 20 ml/kg MS组和TBI + 20 ml/kg MS + Dickkopf-1(DKK-1,Wnt通路的特异性抑制剂)组。通过实时PCR和蛋白质印迹法检测NSE、半胱天冬酶-3、超氧化物歧化酶(SOD)、Wnt3a和β-连环蛋白。在TBI后14天比较每组结果以确定Wnt通路的调节作用。
甲烷生理盐水在TBI后14天内显著抑制炎症、氧化应激和细胞凋亡,从而保护神经元。20 ml/kg MS对TBI的治疗效果最佳。当Wnt通路被抑制时,MS的治疗效果受损。
甲烷生理盐水通过激活Wnt信号通路,发挥其抗炎、抗凋亡和抗氧化作用,从而改善TBI,Wnt信号通路起到了一定作用,但不是MS发挥作用的唯一机制。因此,MS可能是治疗TBI的一种新策略。