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The Role And Mechanism Of HMGB1 In The Improvement Of Transection Of Right Cervical Sympathetic Trunk On Ventricular Remodeling Of Rats With Myocardial Infarction

Posted on:2019-03-04Degree:MasterType:Thesis
Country:ChinaCandidate:S S HeFull Text:PDF
GTID:2394330566482334Subject:Anesthesia
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PART?Effects of transection of right cervical sympathetic trunk on cardiac function and ventricular remodeling after myocardial infarction in ratsObjective:To investigate the effects of transection of right cervical sympathetic trunk on cardiac function and ventricular remodeling after myocardial infarction in rats.Methods:Twenty-four male SD rats were assigned randomly into sham operation group,MI group and MI+TCST group.AMI model was established by ligation of left anterior descending coronary artery in SD rats.TCST model was performed by transection of right cervical sympathetic trunk after left anterior descending coronary artery ligation.Four weeks after operation,the cardiac function of rats were examined by echocardiograph.Hemodynamic change was measured by the right common carotid artery catheterization.Thehearts were harvested to calculate cardiac mass index.Left ventricular myocardium tissues were stained with HE and Masson trichrome.Apoptosis of cardiomyocytes was detected by TUNEL.Protein expression of Bax,Bcl-2,collagen?and collagen III in myocardial tissue were detected by western blot analysis.Results:1.Results of cardiac ultrasonographyCompared with Sham group,LVEDd and LVESd increased,LVEF and LVFS declined in MI group(P<0.05).Rats in MI+TCST group displayed a significant improvement in left ventricular function compared to the MI group(P<0.05).2.Hemodynamic change resultCompared with Sham group,LVSP,+dp/dtmax and-dp/dtmax elevated,and LVEDP decreased in MI group(P<0.05).Compared with MI group,LVSP,+dp/dtmax and-dp/dtmax decreased,LVEDP increased in MI+TCST group(P<0.05).3.Results of cardiac mass indexCompared with Sham group,HW/BW,LVW/BW and LVW/HW increased significantly in MI group(P<0.05).Compared with MI group,HW / BW,LVW / BW and LVW / HW decreased significantly in MI+TCST group(P < 0.05).But there was no significant difference in RVW/HW among three groups(P>0.05).4.Result of HE stainingSham group: myocardial cells were cylindrical,in orderly patterns with nuclei located in the center,and the transverse striation was clearly observable.MI group: the cells at the infarction zone of the left ventricle were shrunken with hyperchromatic cytoplasm,karyopyknosis and karyorrhexis,lysis and breakage of myocardial fibers.The cells damaged in structure were improved in the MI+TCST group,and fibroplasia at the infarction site and inflammatory cell infiltration were reduced.5.Result of cardiomyocyte apoptosisCompared with Sham group,the myocardium protein level of Bax was higher,Bcl-2 was lower and the ratio of apoptotic cells was increased in MI group(P<0.05).Compared with MI group,the myocardium protein level of Bax was lower,Bcl-2 was higher and the ratio of apoptotic cells was decreased in MI+TCST group(P<0.05).6.Result of cardiac fibrosisMasson staining showed that,a large number of collagen fibers were observed,collagen volume fraction increased significantly in MI group(P< 0.05).Compared with MI group,collagen volume fraction declined significantly in MI+TCST group(P<0.05).Western blot results revealed that the content of myocardium collagen and the ratio of myocardium collagen?to III protein in MI group were obviously higher than the Sham group(P < 0.05).The content of myocardium collagen and the ratio of myocardium collagen?to III protein in MI+TCST group were lower than which in MI group(P<0.05).Conclusion1.Right TCST can inhibit myocardial hypertrophy and attenuate ventricular remodeling,improve cardiac function of rats with myocardial infarction.2.Right TCST could significantly decrease the expression of Bax,increase the expression of Bcl-2 and reduce cardiomyocyte apoptosis.3.Right TCST can regulate the expression of type I and III collagen,and reduce the collagen volume fraction of myocardium.PART? Effects of transection of right cervical sympathetic trunk on inflammatory response and HMGB1/TLR4/NF-?B signaling pathway after myocardial infarction in ratsObjective:To investigate the effects of transection of right cervical sympathetic trunk on inflammatory response and HMGB1/TLR4/NF-?B signaling pathway after myocardial infarction in rats.Methods : AMI model was established by ligation of left anterior descending coronary artery in SD rats,then the model rats were randomly divided into MI group and MI+TCST group.TCST model was performed by transection of right cervical sympathetic trunk after left anterior descending coronary artery ligation.The rats in MI group and MI+TCST group were divided into 1,3,7,14,28 d subgroups,and another Sham operation group threading without ligation.The relative m RNA expressions of HMGB1,TNF-? and IL-6 at different time points were detected by quantitative real-time PCR.The protein expressions of HMGB1 and TLR4 at different time points after AMI were detected by Western blot analysis.The effect of right TCST on the expressions of HMGB1 and TLR4/NF-?B signaling pathway was also analyzed.Results1.Expression of HMGB1,TNF-? and IL-6 mRNATNF-? and IL-6,which are early inflammatory factors,increased 1day after MI,peaked at 3 days and gradually decreased thereafter.HMGB1 increased 3 days after MI,peaked at 7 days and gradually decreased.The relative m RNA expression of those inflammatory factors could be reduced by transection of right cervical sympathetic trunk compared with MI group(P<0.05).2.Changes in protein expression of HMGB1 and TLR4 in myocardium tissues at different time after AMIWestern blot results revealed that HMGB1 in the infarct border zone increased in 3 days,and reached its peak at 7 days,then gradually decreased,and at 28 days after MI in MI group was still significantly higher than that in Sham group(P<0.05).TLR4 expression was consistent with that of HMGB1.3.Expression of HMGB1/TLR4/NF?B signaling pathwayThe protein expressions of HMGB1,TLR4,MyD88 and NF-?Bp65 were significantly increased after MI,but were significantly suppressed in MI+TCST group(P<0.05).Conclusion1.Right TCST could reduce the expression of inflammatory factors,thus reduce inflammation.2.Right TCST could reduce the release of HMGB1 and inhibit the activation of TLR4/NF?B signaling pathway,which would be one of the mechanisms that right TCST reduced inflammation after MI.
Keywords/Search Tags:myocardial infarction, ventricular remodeling, transection of right cervical sympathetic trunk, apoptosis, myocardial fibrosis, Inflammation, HMGB1, TLR4/NF-?B signaling pathway
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