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Neuroprotective Mechanisms Of Rutin For Spinal Cord Injury Through Anti-oxidation And Anti-inflammation And Inhibition Of P38 Mitogen Activated Protein Kinase Pathway

Posted on:2019-10-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:H L SongFull Text:PDF
GTID:1364330572454347Subject:Bone surgery
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Objective:Spinal Cord Injury(SCI)is the most serious complication of Spinal Injury,which will not only cause serious physical and psychological damage to the patients themselves,but also cause huge economic burden to the whole society.Although there have been many reports on the treatment of spinal cord injury in China and abroad,the cure is still an unsolved problem.At present,the research on spinal cord injury mainly focuses on the construction of animal model of spinal cord injury and the repair and treatment of the injury model.However,how to obtain a spinal cord injury model consistent with human spinal cord injury and how to repair and treat the obtained spinal cord injury model is the focus of current research.Therefore,the successful construction of an animal model of spinal cord injury has important clinical significance for the treatment of spinal cord injury and is conducive to the in-depth study of the mechanism of spinal cord injury.Methods:The model of rat SCI was established by using Allen's method.HE staining was used for detection.Results and Conclusion:Through the section of T8-T9 spinal segment of the mouse after Allen's attack,HE staining showed that the control group was intact,and the SCI group had pathological changes such as rupture bleeding,indicating successful modeling.Objective:Rutin has anti-inflammatory,antioxidant,anti-viral,anti-tumor and immunoregulatory effects.However,the neuroprotective effect of rutin on spinal cord injury is not clearMethods:The model of rat SCI was established by using Allen's method.The rat model was injected with rutin or MP for 3 consecutive days.After treatment,BBB was used to assess the recovery of motor function.After SCI rutin intervention treatment,to detect the contents of the spinal cord in the inland waters,the NF-?B p65,TNF ?,? and IL-6,IL-1 the inflammatory factor,oxidation factor,BDNF,bFGF and NGF plays and the NT-3 the expression of nerve growth factor.Results:Through the section of T8-T9 spinal segment of the mouse after Allen's attack,HE staining showed that the control group was intact,and the SCI group had pathological changes such as rupture bleeding,indicating successful modeling.After the intervention of rutin and MP in SCI rats,BBB scores increased,but the difference between rutin and MP was not statistically significant(P>0.05).SCI in rats with rutin and MP after the intervention,the spinal cord water content decreased,the NF-?B p65,TNF-?,? and IL-6,IL-1 inflammatory factor levels drop,MDA,SOD,catalase and GSH-Px levels drop,oxidative factors such as BDNF,bFGF and NGF plays and the NT-3 neurotrophic factor expression level increased obviously and no statistically significant difference between rutin and MP(P>0.05).Conclusion:After spinal cord injury using rutin drug intervention treatment,can reduce the water content in the spinal cord,reduce the production of inflammatory cytokines and oxidative stress factor,and promote the secretion of neurotrophic factors,so the rutin after spinal cord injury mainly played an anti-inflammatory,anti-oxidant and promote nerve protective effect of neurotrophic factor secretion.Objective:Rutin has anti-inflammatory,antioxidant,anti-viral,anti-tumor and immunoregulatory effects.However,the neuroprotective effect of rutin on spinal cord injury is not clear.P38 lightning mitogen activated protein kinase(p38 lightning MAPK)pathway is the control of inflammation is the most important member of the MAPK family,and hypertrophic scar and the weaker internal axon growth ability is the main obstacle to the spinal cord to repair,however these processes have been TGF-?/Smad signaling pathways of strictly controlled.We hypothesized that the mechanism of rutin in the repair of spinal cord injury is related to the inhibition of p38 MAPK pathway and TGF-?/Smad signaling pathway.Methods:The model of rat SCI was established by using Allen's method.The rat model was injected with rutin orMP for 3 consecutive days.After treatment p38 lightning MAPK protein expression and activity of caspase-3 and 9,as well as the TGF-?/Smad signaling protein.Results:After SCI in rats with rutin and MP intervention,reduce the caspase-9 in SCI model animal and caspase-3 activity(P<0.05)and apoptosis index the Bcl-2 protein molecule expression level increased,Bax protein molecules expression level decreased,the difference was statistically significant(P<0.05);Value-added index Ki67 protein molecules and PCNA expression levels were significantly increased,and decreased p3 8 lightning MAPK expression,and in total Smad2/3 protein expression level unchanged,under the condition of p-Smad2 and p-Smad3 protein expression level decreased obviously,the difference was statistically significant(P<0.05),and the difference between using rutin and MP has no statistical significance(P>0.05).Conclusion:After spinal cord injury using rutin drug intervention treatment,decreased p38 lightning the expression of MAPK,and suppress the TGF-?/Smad signaling pathways,it shows that it can promote the expression of apoptosis proteins,by reducing and to a certain extent,reduce the generation of fibrous scar in the spinal cord,improve the axon growth ability,to a certain extent protect cells in the spinal cord.
Keywords/Search Tags:Nerve regeneration, Spinal cord injury, Rutin, Oxidative stress, Antioxidants, Anti-inflammatory, P38 MAPK pathway, Resistance to apoptosis, Caspase-3, Caspase-9, TGF-?/Smad signaling pathway
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