Studies On The Protective Effects And Mechanism Of Transaction Of Right Cervical Sympathetic Trunk Combined With Different Analgesics On Ventricular Remodeling After Myocardial Infarction In Rats

Part 1 Effects of transaction of right cervical sympathetic trunk combined with different analgesics on ventricular remodeling after myocardial infarction in rats.Objective To investigate the effects of transaction of right cervical sympathetic trunk combined with different analgesics on ventricular remodeling after myocardial infarction in rats.Methods 36 male SD rats,230-250 g,underwent surgical left anterior descending coronary artery were randomly divided into 6 groups(n=6): sham operation(group Sham),MI control(group MI),the right TCST(group TCST),TCST+parecoxib(group TCST+P),TCST+flurbiprofen(group TCST+F),TCST+ morphine(group TCST+M).After the MI and TCST,rats in group TCST+P,group TCST+F,and group TCST+M were administered with parecoxib(12mg/kg),flurbiprofen(15 mg/kg),and morphine(1.2 mg/kg)respectively by intraperitoneal injectio.Four weeks after the operation,the cardiac function of rats was examined by echocardiograph.Hemodynamic change was measured by the right common carotid artery catheterization.The hearts were harvested to calculate left ventricular hypertrophy index.Left ventricular myocardium tissues were stained with HE and Masson trichrome.The expression of ANP m RNA and BNP m RNA were detected by Sq RT-PCR.The expression of TL-6 m RNA and TNF-? m RNA were determined by q RT-PCR.Results 1 Results of cardiac ultrasonography Reduced cardiac function was observed in group MI compared with it in group Sham(P < 0.05).Rats in group TCST displayed a significant improvement in left ventricular function compared to the MI group(P<0.05).Compared with group TCST,group TCST+P,group TCST+F,and group TCST+M rats had significantly increased LVEF,LVFS vaules,declined LVEDd,LVESd vaules(P<0.05).2 Hemodynamic change result Compared with group Sham,hemodynamic parameters significantly decreased in group MI(P<0.05).Compared with group MI,LVEDP and-dp/dtmax elevated,LVSP and +dp/dtmax decreased in group TCST(P<0.05).Compared with group TCST,LVEDP and-dp/dtmax increased,LVSP and +dp/dtmax decreased in group TCST+P,group TCST+F,and group TCST+M(P<0.05).3 Results of left ventricular hypertrophy index Compared with group Sham,rats in group MI had significantly decreased body weight,elevated HW/BW,(LV+S)/BW,and(LV+S)/HW(P<0.05).Compared with group MI,body weight increased,HW/BW,(LV+S)/BW,and(LV+S)/HW decreased in group TCST(P < 0.05).Compared with group TCST,body weight increased,HW/BW,(LV+S)/BW,and(LV+S)/HW decreased in group TCST+P,group TCST+F,and group TCST+M(P<0.05).4 Results of myocardial morphological changes Group Sham: myocardial cells arranged closely in order,indicating normal myocardial morphology,a small amount inflammatory cells were observed.Group MI: myocardial cells thickening,elongation and arrangement disorder,the collagenfiber of myocardial interstitial increases notably,with lots of inflammatory cells infiltrating.The infarcted border zone of group TCST,group TCST+P,group TCST+F,and group TCST+M showed mild myocardial cell hypertrophy,fibrous hyperplasia and inflammatory cell invasion.5 Expression of ANP m RNA and BNP m RNA The expression of ANP m RNA and BNP m RNA in group MI was significantly increased compared with those in group Sham(P<0.05).Compared with group MI,TCST treatment can reduce the expression of ANP m RNA and BNP m RNA(P<0.05).Compared with group TCST,the expression of ANP m RNA and BNP m RNA was decreased in group TCST+P,group TCST+F,and group TCST+M(P<0.05).6 Expression of TL-6 m RNA and TNF-? m RNA The expression of TL-6 m RNA and TNF-? m RNA in group MI was significantly increased compared with those in group Sham(P<0.05).Compared with group MI,TCST treatment can reduce the expression of TL-6 m RNA and TNF-? m RNA(P<0.05).Compared with group TCST,the expression of TL-6 m RNA and TNF-? m RNA was decreased in group TCST+P,group TCST+F,and group TCST+M(P<0.05).Conclusion 1 Transection of the right cervical sympathetic trunk(TCST)and TCST combined with parecoxib,flurbiprofen and morphine improved cardiac diastolic and systolic function,inhibitied cardiac cell hypertrophy compensatory,and mitigated the process of ventricular remodeling after myocardial infarction in some extent.2 TCST combined with parecoxib,flurbiprofen and morphine respectively were effect in improving the myocardiac function,mitigating the process of ventricular remodeling after myocardial infarction,were superior to TCST theraphy alone.TCST combined with morphine was the most effectively to mitigate the process of ventricular remodeling after myocardial infarction.3 The mechanisms of TCST combined with parecoxib,flurbiprofen and morphine's inhibition of ventricular remodeling after myocardial infarction were possibly due to inhibit sympathetic nervous system activity;reduce the expression of IL-6 and TNF-?,decrease inflammation reaction.Part 2 Studies on the protective effects and mechanism of transaction of right cervical sympathetic trunk combined with different analgesics on ventricular remodeling after myocardial infarction in ratsObjective To investigate the studies on the protective effects and mechanism of transaction of right cervical sympathetic trunk combined with different analgesics on ventricular remodeling after myocardial infarction in rats.Methods 36 male SD rats,230-250 g,underwent surgical left anterior descending coronary artery were randomly divided into 6 groups(n=6): sham operation(group Sham),MI control(group MI),the right TCST(group TCST),TCST+parecoxib(group TCST+P),TCST+flurbiprofen(group TCST+F),TCST+ morphine(group TCST+M).After the MI and TCST,rats in group TCST+P,group TCST+F,and group TCST+M were administered with parecoxib(12mg/kg),flurbiprofen(15 mg/kg),and morphine(1.2 mg/kg)respectively by intraperitoneal injectio.Four weeks after the operation,the hearts were harvested and left ventricular myocardium tissues were stained with Tunel trichrome to calculate the apoptotic index(AI).The expression of PI3 K,Akt,p-Akt,pro-caspase3,and caspase3 were detected by Western blot.Results 1 Results of cardiomyocyte apopt Apoptotic index in group MI was significantly increased compared with it in group Sham(P<0.05).Compared with group MI,TCST treatment can reduce the apoptotic index(P < 0.05).Compared with group TCST,apoptotic index was decreased in group TCST+P,group TCST+F,and group TCST+M(P<0.05).2 Expression of PI3K/Akt signal pathway Compared with group Sham,the expression of PI3 K,p-Akt was decreased,the expression of caspase3 was increased in group MI(P<0.05).Compared with group MI,TCST treatment can increase the expression of PI3 K,p-Akt,reduce the expression of caspase3(P<0.05).Compared with group TCST,the expression of PI3 K,p-Akt was increased,the expression of caspase3 was decreased in group TCST+P,group TCST+F,and group TCST+M(P<0.05).There was no change in the expression of Akt?pro-caspase3(P>0.05).Conclusion The mechanisms of TCST combined with parecoxib,flurbiprofen and morphine's inhibition of ventricular remodeling after myocardial infarction were possibly due to inhibit myocardial apoptosis through activation of PI3K/Akt signaling pathway.