| Objective:As a common disease of the nervous system,stroke is the first cause of death in China,with high morbidity,mortality,recurrence rate and disability rate,which not only seriously affects the quality of life of patients and their families,but also causes a great burden to the society.According to different causes and clinical manifestations,stroke is divided into ischemic stroke and hemorrhagic stroke.Ischemic stroke accounts for more than 80% of the total incidence of stroke,which refers to abnormal nerve damage caused by blood vessel blockage that prevents blood from flowing into the brain.In addition to ischemia,most secondary reperfusion injuries in damaged brain tissues are irreversible.Therefore,research on cerebral ischemia reperfusion injury is of great significance for improving patients’ quality of life,promoting drug research and development,and guiding clinical treatmentCodonopsis can be used as the treatment of apoplexy as recorded in ancient classics.Modern network pharmacological studies show that various active components in Codonopsis have multiple targets to participate in the pathological process of cerebral ischemia reperfusion injury.Experimental pharmacology showed that Codonopsis has important anti-inflammatory,anti-oxidation and free radical scavenging effects in nervous system diseases.Therefore,it is of great significance to study the molecular mechanism of Codonopsis in cerebral ischemia-reperfusion injury.Methods:This paper is divided into three parts.1.Combing TCM theories.Based on the "Chinese Medical Code" 4.0 system,the search was conducted with "Codonopsis pilosula" as the inclusion standard,and the records of Codonopsis pilosula in the treatment of stroke in major medical historical documents before the founding of the People’s Republic of China were dug and collated,and the rules of its syndrome and treatment were analyzed,so as to provide classical theoretical support for the follow-up research.2.Analyze the biological activity network of Codonopsis pilosula.Using network pharmacology technology,data mining method was selected to analyze the potential active components,target,signal pathway and biological process of Codonopsis in the treatment of cerebral ischemia reperfusion injury,so as to provide modern pharmacological reference for experimental research.3.Analyze the functional characteristics of Codonopsis pilosula in the treatment of stroke.By establishing a mouse model of cerebral ischemia-reperfusion injury and giving different doses of Luodangshen oral solution,the molecular mechanism of the treatment of cerebral ischemia-reperfusion injury by the detection of cerebral blood flow imaging,neurological function score,inflammatory factors and reactive oxygen free radicals was explored.Results: 1.Through digging and sorting out the historical literature,it is found that there are 13 ancient books,15 prescriptions and 21 medical records that record Codonopsis pilosia in the treatment of stroke.2.Through network pharmacological study,21 active components and 438 action targets of Codonopsis pilosula were obtained;606 targets of cerebral ischemia reperfusion injury;There were 97 common targets of the party involved in cerebral ischemia reperfusion injury.A total of 1993 biological processes,98 cellular component expression processes and 112 processes related to molecular function were obtained by GO enrichment analysis.KEGG enrichment analysis obtained 156 signaling pathways.3.The experimental study showed that compared with the normal mice,the neurological function score was(3.73±0.17)(P < 0.001),the percentage of blood flow decreased in the ROI area of the cerebral ischemia side of the mouse was increased to(44.83±2.83)(P < 0.001),and the vascular microcirculation became worse.The content of reactive oxygen free radical and inflammatory cytokines ROS,IL-18 and IL-1β in serum of mice were(59.75±3.51)U·m L-1,(226.2±3.03)pg·m L-1 and(235.5±19.7)pg·m L-1,respectively,all of which were increased(P < 0.001),indicating increased inflammation.Increased oxidative stress.Compared with the model group,Ludangshen oral liquid can reduce the neurological function score of mice,and the improvement effect of high dose is the most obvious.The percentage of decreased blood flow in ROI region of cerebral ischemia was decreased in mice,and the most significant was in the high-dose group(17.81±2.82)(P < 0.001).The cerebrovascular microcirculation of mice was improved.The levels of reactive oxygen free radical ROS and inflammatory cytokines IL-18 and IL-1β in serum of mice were decreased(42.48±2.84)U·m L-1,(183.9±20.04)pg·m L-1,and(161.8±10.97)pg·m L-1,respectively(P < 0.01).Oxidative stress is reduced.Conclusion:1.The mechanism of Codonopsis pilosula in improving neurological function after cerebral ischemia/reperfusion injury is supported by the theories of ancient Chinese medicine.2.The 19 active components of Radix Codonopsis can play a role in improving neurological function injury by acting on 97 common targets of Radix Codonopsis involved in cerebral ischemia/reperfusion injury,which may be related to AGe-RAGE pathway,prolactin signaling pathway,sphingolipin signaling pathway,C-type lectin receptor signaling pathway,VEGF signaling pathway,etc.These pathways play important roles in both oxidative stress and inflammation.3.Codonopsis can improve vascular microcirculation by improving behavioral characteristics and cerebral blood flow in mice,and exert antioxidant and anti-inflammatory effects by reducing the expression of ROS,IL-18 and IL-1β,thus exerting protective effects on cerebral ischemia-reperfusion injury in mice. |
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