Role of neurite outgrowth inhibitor-oligodendrocyte myelin glycoprotein/Ras homologous (Rho)-Rho-associated coiled-coil forming protein kinase signaling pathway in acute brain injury of carbon monoxide poisoning rats and treatment feasibility with hydrochloride fasudil
10.3760/cma.j.cn115354-20191218-00756
- VernacularTitle:Nogo-OMgp/Rho-Rock信号通路在CO中毒急性脑损伤中的作用及盐酸法舒地尔治疗的可行性分析
- Author:
Wenwen JIANG
1
;
Weikang BI
;
Zekun LI
;
Li WANG
;
Jinglin WANG
;
Mingjun BI
;
Hai KANG
;
Yong ZOU
;
Qin LI
Author Information
1. 青岛大学基础医学院中西医结合中心，青岛 266071
- Keywords:
Carbon monoxide poisoning;
Acute brain injury;
Hydrochloride fasudil;
Neurite outgrowth inhibitor-oligodendrocyte myelin glycoprotein/Ras homologous (Rho
- From:
Chinese Journal of Neuromedicine
2020;19(5):439-448
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of neurite outgrowth inhibitor (Nogo)-oligodendrocyte myelin glycoprotein (Omgp)/Ras homologous (Rho)-Rho-associated coiled-coil forming protein kinase (Rock) signaling pathway in acute brain injury of carbon monoxide (CO) poisoning rats and treatment feasibility with Rho kinase inhibitor hydrochloride fasudil.Methods:According to random number table method, 135 healthy male SD rats were divided into three groups: a normal control group, a CO poisoning group and a fasudil treatment group ( n=45). Rat models of acute severe CO poisoning were established in the CO poisoning group and fasudil treatment group by inhalation method in a hyperbaric oxygen chamber. All rats received hyperbaric oxygen therapy for two weeks. Rats in the farsudil treatment group were intraperitoneally injected with hydrochloride farsudil for intervention (15 mg/[kg·d], once a d for 2 weeks), while those in the CO poisoning and normal control groups received the same volume of normal saline. The ultrastructures of rat brain tissues were observed by transmission electron microscopy one week after modeling. Staining intensities of Nogo- and OMgp-positive cells were detected by immunohistochemistry, and those of Rock-positive cells were analyzed by immunofluorescence one d, one week, one month and two months after modeling. The protein expressions of Nogo, OMgp and Rock in brain tissues were detected by Western blotting one d, one week, one month and two months after modeling. Results:In the CO poisoning group, the ultrastructures of brain tissues and blood-brain barrier were damaged obviously, and the changes in nucleus, mitochondria and synaptic structure were obvious; while fasudil treatment could effectively maintain the integrity of ultrastructures and functions of brain tissues, and reduce brain edema. One d, one week, one month and two months after modeling, the staining intensities of Nogo, OMgp and Rock positive cells and protein expression levels of Nogo, OMgp and Rock in the CO poisoning group were significantly higher than those in the normal control group at the same time point ( P<0.05); the staining intensities of Nogo, OMgp and Rock positive cells and protein expression levels of Nogo, OMgp and Rock in the fasudil treatment group were significantly lower than those in the CO poisoning group at the same time point ( P<0.05). Conclusion:The activation of Nogo-OMgp/Rho-Rock signaling pathway related molecules (Nogo, OMgp and Rock) is closely related to acute brain injury caused by CO poisoning; hydrochloride fasudil can effectively down-regulate the protein expressions of Nogo, OMgp and Rock, therefore obviously alleviate brain injury after CO poisoning.
