| Background: Spinal cord injury（SCI）is the most serious complication of spinal cord injury,which can lead to dysfunction of the limbs and trunk below the injury site,causing spinal cord edema and cell death at the injury site,resulting in permanent disability and death of patients.Spinal cord injury has a serious impact on the quality of life of patients,causing unbearable psychological and economic stress to patients and families,as well as a heavy burden on society.At present,the research progress of the disease is not satisfactory,and there is no effective treatment method.Ginsenoside Rg1 is one of the important active components of ginseng extract,has a wide range of physiological activities and important medicinal value,has a protective effect on various tissues and organs of the human body,and has anti-apoptosis,antioxidant,anti-inflammatory and neuroprotective effect.The nuclear factor E2-related factor2/heme oxygenase-1（Nrf2/HO-1）signaling pathway is one of the key antioxidant systems involved in maintaining the redox state to defend against intracellular oxidative stress,and it plays an endogenous antioxidant role in central nervous cells to reduce oxidative stress-induced neurons damage.However,it is unclear whether ginsenoside Rg1 is neuroprotective against SCI through the Nrf2/HO-1 signaling pathway.Objectives:In this study,we aimed to explore the potential mechanisms by which ginsenoside Rg1 plays a neuroprotective role in SCI by regulating the Nrf2 / HO-1pathway.Methods : 48 SD rats were randomly divided into 4 groups: sham group,SCI model group（SCI group）,SCI + ginsenoside Rg1 treatment group（Rg1 group）and SCI+ Rg1 + Nrf2 inhibitor ATRA group（ATRA group）,12 animals in each group.The rat model of spinal cord injury was established by the modified Allen’s method.Only the lamina was opened in the rats in the sham group,and the spinal cord was not injured.The Rg1 group was treated with ginsenoside Rg1 for 14 days after spinal cord injury.The Rg1 group was treated with ginsenoside Rg1 for 14 days after the injury,and the ATRA group was treated with ATRA 4 hours before ginsenoside Rg1 treatment.The sham group and the SCI group were injected with the same volume of normal saline.Functional recovery was evaluated according to the Basso,Beattie and Bresnahan（BBB）score at day 1,3,7,14,21 and 28 post surgery;Rats were sacrificed 14 days later,and hematoxylin-eosin（HE）staining was used to observe the structural changes of spinal cord tissue;Relevant biochemical kits were used to detect the levels of superoxide dismutase（SOD）,malondialdehyde（MDA）and glutathione（GSH）in spinal cord tissue;Enzyme-linked immunosorbent assay（ELISA）was used to detect the expression of tumor necrosis factor-α（TNF-α）,interleukin-1β（IL-1β）and interleukin-6（IL-6）in serum;Western blot was used to detect the expression of Nrf2 and its downstream regulatory factor HO-1 protein in spinal cord tissue cells.The expression of HO-1 and Nrf2 m RNA in rat spinal cord tissue was detected by RT-PCR.Results:1.The BBB motor score showed that compared with the Sham group,the motor function of the rats in the SCI group was significantly impaired,and the score was significantly lower（P <0.05）;Compared with the SCI group,the motor function of the rats in the Rg1 group was gradually improved,and the motor score was significantly increased（P< 0.05）;Compared with the Rg1 group,the motor function score of the ATRA group was significantly lower（P< 0.05）.Ginsenoside Rg1 increased motor scores and significantly improved hindlimb motor function in SCI rats.2.HE staining showed that the structure of the spinal cord in the Sham group was normal,and no obvious damage was found.In the SCI group,the boundary between the white matter and gray matter of the spinal cord was blurred,and there were hemorrhage,edema,cyst and cavity formation in the gray matter,degeneration and necrosis of neurons,and infiltration of monocytes and lymphocytes;After treatment with ginsenoside Rg1 in SCI rats,the neuronal edema and hemorrhage in the injured spinal cord were significantly reduced,and the inflammatory cell infiltration,neuronal degeneration and necrosis were also significantly alleviated,and the repair of the damaged spinal cord structure was further promoted;Structural repair of the injured spinal cord was worse in the ATRA group than in the Rg1 group.3.Antioxidative stress indicators showed that compared with the Sham group,the level of MDA in the SCI group was significantly increased（P< 0.05）,and the activities of SOD and GSH were significantly decreased（P < 0.05）;Compared with the SCI group,the Rg1 group had decreased MDA production and increased GSH and SOD activities（P< 0.05）;Compared with the Rg1 group,the ATRA group had higher levels of MDA,and significantly lower levels of SOD and GSH（P< 0.05）.It is suggested that Rg1 protects neurons by inhibiting lipid peroxidation and enhancing antioxidant activity,and plays an important role in alleviating oxidative stress injury secondary to SCI.4.The detection of inflammatory factors showed that compared with the Sham group,TNF-α,IL-1β and IL-6 in the SCI group were significantly increased（P<0.05）;Compared with the SCI group,the inflammatory cytokines in the Rg1 group were significantly decreased（P<0.05）;Compared with the Rg1 group,the levels of inflammatory factors in the ATRA group were significantly increased（P<0.05）.This suggests that ginsenoside Rg1 can alleviate the inflammatory response after SCI.5.Western blot and RT-PCR showed that compared with the Sham group,the protein expression and m RNA levels of Nrf2 and HO-1 in the SCI group were significantly decreased（P< 0.05）;Compared with the SCI group,the protein and m RNA levels of Nrf2 and HO-1 in the Rg1 group（P< 0.05）;compared with the Rg1 group,the protein and m RNA levels of Nrf2 and HO-1 in the ATRA group were significantly decreased（P< 0.05）.It is suggested that ginsenoside Rg1 can increase the protein and m RNA expression of Nrf2 and HO-1 in injured spinal cord tissue after SCI.Conclusion:Ginsenoside Rg1 has a neuroprotective effect on SCI and can improve motor dysfunction caused by injury.The underlying mechanism may play antioxidative stress and anti-inflammatory effect by regulating the Nrf2/HO-1 signaling pathway. |
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