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Effects Of Inhibiting The Activation Of Astrocytes In Spinal Cord And Dorsal Root Ganglion On Myocardial Ischemia-reperfusion Injury In Rats And Its Mechanisms

Posted on:2020-01-22Degree:MasterType:Thesis
Country:ChinaCandidate:R R LiuFull Text:PDF
GTID:2404330575989734Subject:Anesthesia
Abstract/Summary:PDF Full Text Request
Background and Objectives:Ischemic cardio myopathy is one of the most common diseases in the chronic diseases of our country.Coronary artery reperfusion is an effective treatment for this kind of disease.However,reperfusion itself will further aggravate myocardial injury,so how to reduce myocardial ischemia reperfusion injury is the key point to treat ischemic heart disease.Astrocytes are the most glial cells in the central nervous system,function as supporting nutrition for central nervous system,and are related to generation and maintenance of pain caused by nociceptive sense.Damaged myocardium can release inflammatory mediators such as H+,adenosine and bradykinin during myocardial ischemia-reperfusion,which can sensitized cardiac afferent neurons.The nociceptive signal transmitted from the heart to the dorsal root ganglion and then transferred to the spinal cord and the high center of the corresponding segment.The spinal cord and dorsal root ganglion contain a large number of astrocytes,and nociceptive afferent signals activate astrocytes in spinal cord and DRG.A large amount of cytokines can be released from astrocytes after activated,astrocytes also promotes the release of substance p and excitatory amino acids from the terminal,including primary human neurons,and triggers a series of complex reaction processes all of these further aggravate myocardial damage.Therefore,inhibiting the activation of astrocytes may alleviate myocardial ischemia reperfusion injury.The aim of this study was to investigate the effects of inhibition of astrocyte activation on myocardial ischemia-reperfusion injury in rats and its mechanism.Method : Healthy adult male SD rats,weighing 250-300 g,in which intrathecal catheterization successfully without infection and motor sensory disorder.The experiment is divided into two parts.Part 1: Activation of spinal cord and DRG astrocytes during myocardial ischemia reperfusion injury.The thoracic spinal cord(T2-6)and DRG tissues were acquired at different time points during myocardial ischemia-reperfusion(before ischemia,30 minutes after ischemia,10 minutes and 120 min after reperfusion)for detected the expression of GFAP protein by Western blot of rats,and the myocardial infarction volume and cardiac troponin I of the four time points were measured.Part 2: Effect of intrathecal injection of astrocyte inhibitor on myocardial ischemia-reperfusion injury and its mechanism.The rats were randomly divided into four groups: sham operation group(SHAM group),ischemia reperfusion group(I/R group),astrocyte inhibitor treatment group(I/R +FC group),fluorine citrate control group(FC group).The I/R+FC group was treated with three different dose of fluoride citrate(low,medium and high dose).SHAM group and FC group only did sham-operation as thoracotomy and without ligation of left anterior descending coronary artery.FC group rats received 10 ?l(1 nmol)of fluoride-citrate(1nmol)after thoracotomy.I/R group and I/R+FC group were ligated the left anterior descending coronary artery for 30 min and reperfusion for 120 min,The I/R+FC group received intrathecal infusion of 10 ?l citrate fluoride(1 nmol)at 30 min before ischemia,but the I/R+FC group received intrathecal injection of citrate fluoride 10 ?l(1 nmol)30 min before ischemia operation.The blood pressure,heart rate and electrocardiogram were recorded during ischemia and reperfusion.At the end of reperfusion,myocardial tissue was collected and myocardial infarction area(IS)was measured to calculate the volume ratio of infarct area by the ratio of ischemic risk area(AAR)and infarction area(IS).T2-6 spinal cord and DRG tissue were collected to detect the expression of GFAP in spinal by Western blot and immunofluorescence,and the expression of trpv1,trka,NGF in spinal and DRG by Western blot.The serum was collected to detection the of concentration CTn I.Result 1.To investigate the activation of astrocytes in spinal cord and DRG after myocardial ischemia-reperfusion injury.The results showed that the expression of GFAP in spinal cord and DRG increased gradually with the prolongation of myocardial ischemia-reperfusion time.The expression of GFAP in spinal cord and DRG was significantly increased after reperfusion for 120 min.These results suggest that myocardial ischemia-reperfusion injury can activate astrocytes and increase the expression of GFAP.2.To investigate the effect of intrathecal injection of astrocyte inhibitor on myocardial ischemia-reperfusion injury in rats and its mechanism.1).Effects of different dose of fluoride citrate on myocardial ischemia reperfusion injury.The results of myocardial ttc staining and CTn I detection showed that 10 ?l(1 nmol)fluoride citrate could minimize myocardial infarction size and decrease the concentration of serum CTn I after myocardial ischemia reperfusion.2).Effects of inhibition of astrocyte activation on myocardial ischemia-reperfusion injury and its mechanism.Effects of inhibition of astrocyte activation on myocardial ischemia-reperfusion injury in rats: IS/AAR,arrhythmia score and serum CTn I concentration increased after myocardial ischemia-reperfusion injury.Intrathecal administration of sodium fluoride citrate inhibited the increase of IS/AAR,arrhythmia score and CTn I concentration in serum.Effects of inhibition of astrocyte activation on GFAP,trpv1,trka,NGF expression in spinal cord and DRG: Intrathecal infusion of fluoride citrate inhibits the activation of astrocytes in spinal cord and DRG,and reduces the increase of GFAP,trpv1,trka,NGF expression in spinal cord and DRG after myocardial ischemia-reperfusion injury.Conclusion Astrocytes can be activated and the expression of GFAP in spinal cord and DRG increased after myocardial ischemia-reperfusion injury.The astrocytes in spinal cord and DRG can be inhibited by intrathecal infusion of sodium fluoride citrate,which decreased the occurrence of arrhythmias,the concentration of CTn I,and the expression of GFAP,trpv1,trka,NGF in spinal cord and DRG after during myocardial ischemia-reperfusion injury.
Keywords/Search Tags:ischemia reperfusion injury, astrocyte, fluoride citrate, spinal, dorsal root ganglion
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