Effect Of Perillaldehyde On Myocardial Ischemia-reperfusion Injury In Rats Through PI3K/Akt Pathway

Background: revascularization is achieved through interventional therapy after acute myocardial infarction,but complications such as arrhythmia and heart failure after reperfusion,if not timely and effective intervention,will seriously affect the cardiac function of patients,and even threaten their life safety.We aimed to determine the effect of Perillaldehyde on myocardial ischemia/reperfusion injury in rats and analyze its mechanism.Objective: By establishing a rat model of myocardial ischemia/reperfusion injury,to study the effect of Perillaldehyde on myocardial ischemia/reperfusion injury and its mechanism,so as to provide an important theoretical basis for clinical intervention of myocardial ischemia-reperfusion injury and find drug treatment targets.Methods: Myocardial ischemia/reperfusion model was established by ligation of left anterior descending branch.The rats were randomly divided into sham operation group（SO group）,ischemia-reperfusion group（I/R group）,perillaldehyde 18.0,36.0,72.0 mg/kg pretreatment group and PI3K/Akt pathway inhibitor（LY294002）group.The animal model was established after continuous intragastric（Ig）for 7 days: the SO group was only threaded without ligation during operation,the SO group and I/R group were given 0.5% Carboxy cellulose for 1 week（W）before operation,In PAH group,18.0,36.0 and 72.0 mg/kg PAH were administered by intragastric for 1 W before operation.The cardiac troponin I（cTnI）,creatine kinase（CK）and lactate dehydrogenase（LDH）were detected.The score of myocardial injury was evaluated to select the optimal dose of perillaldehyde on myocardial ischemia/reperfusion injury;then use the optimal dose of perillaldehyde to establish the PI3K/Akt pathway inhibitor（LY294002）group（0.3mg/kg LY294002+PAH+I/R group）.PAH was administered by intragastric for 1 W before ligation,and the inhibitor was injected into the tail vein minutes before ligation,to detect serum cTnI,CK and LDH.The expression levels of tumor necrosis factor-α,interferon-?,interleukin 6（IL-6）,superoxide dismutase（SOD）,glutathione peroxidase（GSH-Px）,malondialdehyde（MDA）were detected by ELISA,the expression levels of apoptosis and autophagy related proteins（Bcl-2,Bax,LC3B,Beclin-1）and PI3K/Akt signaling pathway proteins were measured by Western blot,and the apoptosis index was calculated and compared.Results: Comparison of different dose groups:（1）the level of cTnI in PAH36+I/R and PAH72+I/R groups were lower than that in I/R group,and the levels of CK and LDH in PAH18+I/R group,PAH36+I/R group and PAH72+I/R group were lower than the I/R group,the difference was statistically significant（P<0.05）;Compared with PAH18+I/R group,the level of cTnI,CK in PAH36+I/R group and PAH72+I/R group decreased significantly,the level of LDH in PAH72+I/R group decreased,the difference was statistically significant（P<0.05）;The levels of serum CK and LDH in PAH72+I/R group decreased than those in PAH36+I/R group,the difference was statistically significant（P<0.05）.（2）the myocardial injury score of rats in PAH36+I/R injury group and PAH72+I/R injury group was significantly lower than that in I/R injury group and PAH18+I/R injury group（P<0.05）.Combined with the above results,the optimal dose of perillaldehyde was 36.0 mg/kg.Comparison of test results after using the optimal dose of Perillaldehyde:（1）compared with I/R group,in the PAH36+I/R group and LYPAH36+I/R group,the levels of cTnI,CK,LDH,TNF-α,IFN-?,IL-6 decreased,the levels of SOD and GSH-Px were significantly higher,the MDA decreased,LC3 B and Beclin1 decreased,Bcl2 increased,Bax and the apoptosis index decreased,the P-AKT was higher,the difference was statistically significant（P<0.05）;（2）Compared with PAH 36+I/R group,in the LYPAH36+I/R group,the levels of cTnI,CK,LDH,TNF-α,IL-6 increased,the levels of the SOD and GSH-Px decreased,the MDA increased,LC3 B and Beclin1 increased,the level of Bcl2 decreased,Bax increased,the ratio of Bcl2/Bax decreased and the level of apoptosis increased,and P-AKT decreased,the difference was statistically significant（P<0.05）.Conclusion: Perillaldehyde can reduce myocardial ischemia/reperfusion injury in rats,and the myocardial protective effect of PAH may be related to regulating inflammatory response and reducing autophagy through PI3K/Akt pathway.The activation of this signal pathway finally inhibits the apoptosis induced by myocardial ischemia/reperfusion.