The Research On The Protective Effect Of Sulforaphane On Radioactive Myocardial Damage In Mice

Background and objective:Radiotherapy has a clear therapeutic status in the treatment of thoracic solid tumors and early malignant lymphoma.However,ion-irradiation(IR)not only prevented the proliferation and growth of tumor cells,but also caused radioactive myocardial damage.Oxidative stress is one of the main pathogenesis of radioactive myocardial damage,so inhibiting oxidative stress in myocardial tissue caused by IR may be an effective treatment.Antioxidants are the first line of defense against oxidative stress damage.However,the effects of exogenous antioxidants are temporary and may have many side effects.Therefore,mobilizing endogenous antioxidant system may be an effective method to reduce radioactive myocardialdamage.Although sulforaphane(SFN)is an exogenous antioxidant,the difference is that SFN can also activate endogenous antioxidant system by activating Nuclear factor erythroid 2-related factor 2(Nrf2)to resist heart damage related to oxidative stress caused by various factors.Therefore,the primary purpose of this study is to determine whether SFN can inhibit oxidative stress in myocardial tissue and alleviate heart damage caused by IR.On this basis,we will also explore whether the protective effect of SFN on the heart is related to the upregulation of Nrf2 under IR conditions.In order to provide a theoretical basis for the exploration of effective protective agents and therapeutic drugs of RIHD.Methods:The 8-week-old male ICR mice were randomly divided into 3 groups: control group,IR group and IR+SFN group.The IR group and IR+SFN group were treated with single irradiation of the heart(225 KV/13.33 m A high-energy X-ray,the X-ray was filtered by 3mm aluminum and 1.85 mm copper,circular IR field with diameter of1 cm,dose rate of 1Gy/min,2000 c Gy/20 Gy in total),and the unirradiated part was shielded by 1cm thick lead plate.Mice in the IR+SFN group received subcutaneous injection of SFN(0.5mg/Kg)for 5 consecutive days per week.At the 4th week after the initial modeling,mice were examined with Doppler echocardiography to detect the structure and function of the heart,and then mice were sacrificed.The heart is divided into two parts after weighing,one part of the cardiac tissue were collected for sirus red and HE staining,and protein were extracted from the other part for detection of related indicators,including the expression of CTGF,Nrf2 and C-Cas-3,the content of MDA.In addition,left tibial length of mice were measured to calculate the heart weight/tibial length ratio to evaluate the degree of cardiac hypertrophy of mice.Results:IR can cause ventricular dilation,myocardial hypertrophy and decreased cardiac function in mice,SFN treatment can effectively improve cardiac structure and cardiac dysfunction.IR can destroy the myocardial structure of mice and increase the deposition of collagen fibers in myocardium,and SFN can effectively inhibit the above pathological changes and reduce myocardial fibrosis in mice.IR significantly increases the content of malonaldehyde(MDA),an indicator of myocardial lipid peroxidation,and SFN treatment reduces the content of MDA.IR increased the expression of Nrf2,and SFN further up-regulated the expression of Nrf2 in myocardium.Conclusion:IR can cause oxidative stress in myocardial tissue,lead to myocardial lipid peroxidation,and lead to changes in cardiac structure and function.IR-induced up-regulation of Nrf2 may be the result of compensatory up-regulation of myocardial tissue against oxidative stress.SFN alleviated radioactive myocardial damage,which may be associated with up-regulation of Nrf2 expression.