| BackgroundStroke is one of the most important fatal diseases in the world.After cerebral ischemia,blood vessels are blocked by thrombus,blood supply to the brain is blocked,and neurons around the blood vessels die because they are not supplied in time.The well-recognized effective stroke treatment drug t PA is a thrombolytic drug.Its treatment time window is narrow and the indications are strict.Few patients can benefit in time.At present,in addition to thrombolysis,the international research is to induce differentiation of endogenous neural stem cells so that they can migrate to the ischemic brain area and solve the problem of neuron survival in the ischemic brain area.Catalpol is the main component of the traditional Chinese medicine Rehmannia glutinosa.The previous results of the research team found that catalpol has a neuroprotective effect on the acute phase of cerebral ischemia,and has a benign regulatory effect on neurovascular remodeling in the middle and late stages,and can also promote permanent focal brain Proliferation of neural stem cells in the SVZ zone of ischemic rats.However,because the vascular microsystem of the ischemic brain has not been reconstructed,it is a question whether new neurons can migrate to the ischemic brain to differentiate and survive.During cerebral ischemia,if there are drugs that can promote the regeneration of neural stem cells,it can also promote the improvement of the microenvironment of the cerebral ischemic area,create conditions for the colonization of new neurons in the ischemic brain area,and promote the survival of the new nerves in the ischemic brain area.,To reduce the disability rate of stroke,which has important scientific value and clinical significance for the treatment of stroke.ObjectiveThis project intends to further explore the improvement effect of catalpol administration on cortical infarction and vascular blockage of cerebral ischemia rats on the basis of preliminary experiments of the research group,and evaluate the effect of neurological function recovery at the corresponding time point in cerebral ischemia rats,To observe the survival of related cells in the ischemic cerebral cortex,and provide an experimental basis for the follow-up study of catalpol on the survival of newborn neurons in the ischemic brain area.Methods1.Prepare a focal permanent cerebral ischemia model by electrocoagulation in healthy adult male SD rats,and randomly divide them into a sham operation group,a model group,and an administration group 1h after modeling(administration dose 5mg/kg,10mg/kg),24 hours after modeling(administration dose 5mg/kg,10mg/kg),the administration group was intraperitoneally injected with catalpol according to the dose,and the control group was injected with the same dose of normal saline,once a day,continuous Administration for 7days.Behavioral evaluations were performed 1,4,7,14,21,28 days after modeling,and the neurological function recovery of rats with cerebral ischemia at the corresponding time points after the administration of catalpol was evaluated.2.Infuse healthy SD rats with gelatin ink of different concentrations and different doses(15%,20%,25%;5ml,10 ml,15ml),and observe and compare brain tissue samples,and select the appropriate concentration and dose.According to the first chapter,the animal models are grouped.4d,7d,14 d,21d after the administration of the model,the blood vessels are displayed by the gelatin ink perfusion method,photographed and analyzed,combined with TTC staining,and preliminary observations are made of cerebral ischemia after catalpol administration.Recovery of infarction and vascular blockage in the cortex of rats.3.According to the first chapter,the animal models are grouped,and the samples are taken 4d,7d,14 d,21d after the model is administered,and the immunohistochemical markers Brd U,GFAP,Nestin are expressed in the ischemic cortex of cerebral ischemia rats In order to determine the intervention of catalpol on related cells in the ischemic cortex after cerebral ischemia.Results1.Behavioral results show that compared with the model group,the catalpol administration group promotes the weight gain of cerebral ischemia rats to varying degrees,reduces the Bederson score and m NSS score of cerebral ischemia rats,and reduces cerebral ischemia.The rat’s biased use of the non-injured side forelimbs significantly improved the score at 7 days after surgery,and basically returned to the sham operation level at 21 days.2.Select 20% gelatin ink concentration and 5ml gelatin ink perfusion concentration and dosage.The statistical results show that the administration of catalpol can improve the infarction of the ischemic brain area in the acute phase of middle artery embolization.At 14 days after the operation,It can be seen by naked eyes that the embolized middle artery in the ischemic cerebral area of ??the catalpol administration group is almost unblocked,and it is higher than the self-repair level of the model group.3.Compared with the model group,after 7 to 21 days,catalpol administration promoted cell proliferation in the cerebral ischemic cortex of rats with permanent focal cerebral ischemia.At 4 and 7 days,the formation of astrocytes in the cerebral ischemic cortex of the 1h catalpol administration group was more obvious than that in the model group(P<0.05).It is speculated that catalpol promotes the regeneration of astrocytes to secrete neurotrophic active substances and promote nerves Cell survival,axon regeneration,and synapse shaping.By the 21 st day,the catalpol administration group can slow down the number of astrocytes.It is speculated that catalpol can reduce the excessive proliferation of astrocytes and at the same time reduce the occurrence of neuroinflammation.5.After cerebral ischemia,the number of Nestin positive cells in each experimental group increased,and the number of positive cells decreased with the passage of time.The number of Nestin positive cells in both the administration group and the model group was higher than that in the sham operation group,and the expression of Nestin decreased and returned to the level of the sham operation group at 21 days.Conclusion1.Catalpol can promote the weight gain of rats with focal permanent cerebral ischemia,promote the improvement of their neurobehavioral scores,and improve their biased use of non-injured forelimbs.2.Using gelatin ink combined with TTC staining method,it is proved from a macro perspective that catalpol can promote the improvement of cortical infarction and vascular blockage in cerebral ischemia rats.3.Catalpol promotes cell proliferation in the ischemic cerebral cortex area,and has a dual regulatory effect on astrocytes.It not only helps activate,provides neurotrophic substances,and promotes neuron survival;it also inhibits the excessive proliferation of astrocytes and prevents The excessive proliferation of astrocytes leads to neuroinflammation and scarring,which affects the migration of new neurons.It provides a good microenvironment for the migration of neonatal neurons to the ischemic cortex in the later stage. |
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