Liu Xuehua, Liang Fang, Zhang Jing, Li Zhuo, Yang Jing, Kang Nan
Department of Hyperbaric Oxygen Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Front Neurol. 2020 Oct 15;11:563281. doi: 10.3389/fneur.2020.563281. eCollection 2020.
Intestinal barrier dysfunction is often observed clinically after spinal cord injury (SCI) and seriously affects long-term quality of life. Hyperbaric oxygen (HBO) treatment has been proved to promote barrier function recovery after injury, but the influence of HBO on intestinal barrier function following SCI is unclear. We aimed to investigate the effect and mechanisms of HBO treatment on intestinal barrier function by measuring the level of tight junction (TJ) proteins and the Ras homolog (Rho)/Rho-associated coiled-coil forming protein kinase (ROCK) signaling pathway. SCI model was established in rats, and the animals were randomly assigned into three groups: sham-operation group (SH), SCI group and SCI+HBO group. In the SCI+HBO group, the rats inhaled 100% O for 1 h at 2.0 atmospheres absolute pressure (ATA) once per day after surgery. Neurological function and intestinal permeability were assessed after surgery, and the jejunum tissue was excised for histological and intestinal barrier function evaluations. The protein levels of TJ and the Rho/ROCK signaling pathway were also measured. The results showed that in the SCI group, intestinal mucosal injury score, intestinal permeability, and levels of Rho and ROCK1 were higher, and TJ proteins occludin and ZO-1 were lower than those in the SH group ( < 0.01). HBO treatment significantly inhibited the expression of Rho and ROCK1, increased occludin and ZO-1 expression, decreased intestinal permeability, and alleviated intestinal mucosal injury as compared with the SCI group ( < 0.05, < 0.01). The SCI+HBO group showed higher Basso-Beattie-Bresnahan (BBB) scores relative to the SCI group on postoperative days 7 and 14 ( < 0.01). There was a significant negative correlation between BBB score and intestinal mucosal injury score in rats after HBO treatment ( < 0.05). We concluded from this study that HBO treatment promoted the expression of TJ proteins possibly through inhibiting Rho/ROCK signaling pathway, which protected the intestinal barrier function and improved the intestinal permeability after SCI in rats.
脊髓损伤（SCI）后临床上常观察到肠道屏障功能障碍，这严重影响长期生活质量。高压氧（HBO）治疗已被证明可促进损伤后屏障功能恢复，但HBO对SCI后肠道屏障功能的影响尚不清楚。我们旨在通过测量紧密连接（TJ）蛋白水平和Ras同源物（Rho）/Rho相关卷曲螺旋形成蛋白激酶（ROCK）信号通路来研究HBO治疗对肠道屏障功能的作用及机制。在大鼠中建立SCI模型，并将动物随机分为三组：假手术组（SH）、SCI组和SCI + HBO组。在SCI + HBO组中，大鼠术后每天在2.0绝对大气压（ATA）下吸入100%氧气1小时。术后评估神经功能和肠道通透性，并切除空肠组织进行组织学和肠道屏障功能评估。还测量了TJ蛋白水平和Rho/ROCK信号通路。结果显示，与SH组相比，SCI组的肠黏膜损伤评分、肠道通透性以及Rho和ROCK1水平更高，而TJ蛋白occludin和ZO - 1更低（<0.01）。与SCI组相比，HBO治疗显著抑制了Rho和ROCK1的表达，增加了occludin和ZO - 1的表达，降低了肠道通透性，并减轻了肠黏膜损伤（<0.05，<0.01）。在术后第7天和第14天，SCI + HBO组相对于SCI组的Basso - Beattie - Bresnahan（BBB）评分更高（<0.01）。HBO治疗后大鼠的BBB评分与肠黏膜损伤评分之间存在显著负相关（<0.05）。我们从这项研究得出结论，HBO治疗可能通过抑制Rho/ROCK信号通路促进TJ蛋白的表达，从而保护大鼠SCI后的肠道屏障功能并改善肠道通透性。
