补骨脂酚调控p53介导的铁死亡对心肌缺血再灌注损伤的影响研究OA

Objective It is to investigate the effect and mechanism of action of bakuchiol on ferroptosis of cardiomyo-cytes after myocardial ischemia-reperfusion injury(MIRI)in rats.Methods Fifty SD rats were randomly divided into sham operation group,model group,low-dose bakuchiol group,high-dose bakuchiol group and high-dose bakuchiol+Nutlin-3a group,with 10 rats in each group.The rats in the low-dose and high-dose bakuchiol groups were given bakuchiol 2.5 and 5 mg/kg via gavage,respectively,and the rats in the high-dose bakuchiol+Nutlin 3a group were given bakuchiol 5 mg/kg via gavage and Nutlin-3a 25 mg/kg via intraperitoneal injection,all once daily.After 5 days of treatment,the rats of all groups except for the sham operation group were prepared to establish models of MIRI.At 24 hours after surgery,the serum levels of creatine kinase isoenzyme(CK-MB)and lactate dehydrogenase(LDH)were measured by ELISA,the myocardial pathological damage and iron deposition were observed by HE staining and Prussian blue staining,the contents of ferrous ions(Fe2+),malondialdehyde(MDA)and glutathione peroxidase(GSH)in myocardial tissue were measured by kits,the flu-orescence intensity of reactive oxygen species(ROS)in myocardial tissue were detected by dihydroethidium(DHE)stai-ning,the positive expression of p53 protein in myocardial tissue was detected by immunohistochemistry staining,and the protein expressions of p53,solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)in myo-cardial tissue were measured by Western Blot.Results Compared with the sham operation group,the serum levels of CK-MB and LDH of rats were significantly increased in the model group(both P<0.05);damage to cardiomyocytes and myo-cardial fibers were found;the proportion of iron deposition,contents of Fe2+and MDA,fluorescence intensity of ROS,mean optical density of p53-positive expression,and relative expression of p53 protein in myocardial tissue were all signifi-cantly increased(all P<0.05),while the content of GSH and relative protein expressions of SLC7A11 and GPX4 in myo-cardial tissue were all significantly reduced(all P<0.05).Compared with the model group,the serum levels of CK-MB and LDH of rats were significantly increased in the low-dose bakuchiol group and high-dose bakuchiol group(all P<0.05);the cardiomyocytes and myocardial fibers damages were alleviated;the proportion of iron deposition,contents of Fe2+and MDA,fluorescence intensity of ROS,mean optical density of p53-positive expression,and relative expression of p53 protein in myocardial tissue were all significantly decreased(all P<0.05),while the content of GSH and relative pro-tein expressions of SLC7A11 and GPX4 in myocardial tissue were all significantly increased(all P<0.05).Compared with the high-dose bakuchiol group,the myocardial damage in the high-dose bakuchiol+Nutlin-3a group was aggravated,and all of the aforementioned diagnostic indicators were reversed,the differences were all statistically significant(all P<0.05).Conclusion Bakuchiol can inhibit myocardial ferroptosis in MIRI rats via down-regulating expression of p53,there-by alleviate myocardial injury.