Asiatic Acid Improve Radiation Induced Heart Damage Through Anti-Oxidative Stress And Anti-Fibrosis In Mice

Objective : By observing the effect of traditional Chinese medicine asiatic acid(AA)on the degree of radiation-induced cardiac injury(RIHD)in mice,the protective effect of the drug on RIHD in mice was studied,and the protective mechanism of the drug was preliminarily discussed,aiming to provide a reference for the protection of RIHD.Methods : According to the random number table method,10 male C57BL6 mice were divided into 3 groups : blank control group(group A);simple irradiation group(group B);irradiation + AA administration group(group C).Group A mice did not undergo any intervention throughout the experiment;the mice in group B and group C were irradiated with X-ray at the second week of the experiment.The mice in group B and group C were intragastrically administered with normal saline and the same volume of AA at a concentration of 100 mg / kg every day from the first day.1.Radiation treatment : At the beginning of the second week of the experiment,the precordial area of mice in group B and group C was fully exposed to a linear accelerator and irradiated with a dose of 15 Gy using 6MV-X ray;2.Non-control group treatment : One week before irradiation,mice in group C were given AA(100mg / kg)by gavage once a day until the end of the experiment.Mice in group B were given the same quality of normal saline at the same time every day until the end of the experiment.3.At the 8th week after irradiation,the cardiac systolic function of mice was evaluated by small animal echocardiography.4.Morphological observation : At the 8th week after irradiation,the mice were sacrificed after the end of echocardiography,and the morphological changes of myocardial tissue were observed by hematoxylin-eosin(HE)staining;masson staining was used to detect the degree of myocardial fibrosis in mice;5.Biochemical detection : WB and other methods were used to detect the expression levels of HO-1,TGF-β1 and Smad2 / 3 proteins in mouse heart tissue.Results:1.General situation of mice : At the 8th week after irradiation in the precardiac area,the mice showed inactive activity,weakened feeding and water intake,and obvious hair removal and hair whitening in the irradiated area;2.Cardiac color Doppler ultrasound showed that the cardiac systolic function(EF,FS)of mice in the irradiation + AA administration group was improved compared with the simple irradiation group,but still lower than the blank control group;3.The results of HE staining and Masson staining showed that except for group A,the myocardial tissues of mice in other groups showed different degrees of pathological changes,mainly inflammatory reaction and perivascular fibrosis.Myocardial edema,myocardial cell disorder,myocardial interstitial inflammatory cell infiltration,but the myocardial injury in group C was less than that in group B,and the degree of myocardial fibrosis in group C was also less than that in group B.4.WB results showed that the positive expression rates of HO-1,TGF-β1 and Smad2 / 3 protein in myocardial tissue of mice in each group were significantly different(P < 0.05).Compared with the blank control group,the expression of HO-1,TGF-β1 and Smad2 / 3 in myocardial cells of mice in the simple irradiation group was significantly increased.Compared with the irradiation group,the expression levels of HO-1,TGF-β1 and Smad2 / 3 in cardiomyocytes of mice in the AA intervention group were decreased,but still higher than those in the blank control group.Conclusion:1.The RIHD animal model can be successfully established by using 6MV-X-ray15 Gy single irradiation of the precardiac area of C57BL6 mice for 8 weeks.2.At 8 weeks after radiation,inflammation and fibrosis can occur in the myocardium of mice,which may be related to the increased expression of TGF-β1 and Smad2 / 3 in myocardial tissue.3.AA administration can reduce the expression of HO-1 protein,reflecting the reduction of oxidative stress level in myocardial tissue,and AA can reduce myocardial fibrosis injury induced by radiation in mice.Its cardiac protection mechanism may be related to the reduction of oxidative stress level in myocardial tissue,but its specific pathway and mechanism are not yet fully clear,and further research is needed.