The Role Of Oxidative Stress On Hyperthyroid-Induced Cardiomyopathy And The Effect Of Potentilla Anserine L.on It

Objective: Hyperthyroidism is an important factor for cardiovascular disease and can lead to cardiac hypertrophy or even heart failure if not treated effectively.At present,the pathogenesis and therapeutic drugs of hyperthyroidinduced cardiomyopathy are still not clear.The purpose of this study is to explore the oxidative stress mechanism as hyperthyroid-induced cardiomyopathy and the potential role of Potentilla anserine L.in the regulation of hyperthyroid-induced cardiomyopathy.Methods: Sixty male healthy Kunming mice were randomly assigned to 3 groups: the control group(Con group),hyperthyroidism model group(T4 group)and Potentilla anserine L.treatment group(T4+PAL group),with 20 in each group.The mice in T4 group and T4+PAL group were intraperitoneally injected with T4 diluent at a dose of 1mg/kg to construct the animal model of hyperthyroidism.The Con group was given the same dose of saline solution every other day for 7 weeks.Moreover,the mice in T4+PAL group were injected with Potentilla anserine L.solution at a dose of 3.6g/kg by gavage,and the mice in the Con group and T4 group were given the same dose of 0.3%carboxymethyl cellulose suspension by gavage every two days for 7 weeks.Intragastric administration was always given after intraperitoneal injection.After the modeling,the mice were weighed,anaesthetized and dissected for cardiac sampling,and the length of the tibia was also measured.RT-PCR was performed to measure the m RNA levels of atrial natriuretic peptide(ANP)and β-myosin heavy chain(β-MHC).H&E and Masson staining were employed to observe cardiac histological changes.Oxidative stress levels of Reactive Oxygen Species(ROS),malondialdehyde(MDA)and Superoxide dismutase(SOD)were monitored by detection kits.Western blot was used to detect the 4-Hydroxynonenal(4-HNE)modified proteins and the caspase3 level.Immunohistochemistry was used to observe the distribution and expression of 4-HNE in heart.Cardiomyocyte apoptosis was evaluated by TUNEL assay.Results:After the modeling,the body weight and heart weight of the mice were measured.It was found that compared with the Con group,the body weight in T4 group and T4+PAL group were decreased,the heart weight and size,heart weight/body weight ratio and heart weight/tibial length ratio increased significantly.The m RNA levels of ANP and β-MHC were up-regulated.cardiomyocyte crosssectional area and cardiac fibrosis were aggravated(P<0.05).Oxidative stress results showed that compared with the Con group,the content of ROS and MDA aldehyde product increased in heart,and the ability of SOD to scavenge free radicals decreased in T4 and T4+PAL groups.It was further observed that 4-HNE modified proteins level increased after excessive L-thyroxine treatment,and the lipid peroxidation product 4-HNE mainly distributed around blood vessels,but there were no significant changes in the caspase3 protein and cardiomyocyte apoptosis.In addition,compared with the hyperthyroidism model group,the heart index and oxidative stress indicators of Potentilla anserine L.intervention did not change significantly.Conclusions: The mechanism of hyperthyroid-induced cardiomyopathy is related to the increased oxidative stress,but do not include apoptosis mechanism.Unfortunately,Potentilla anserine L.has no obvious protective effect on hyperthyroid-induced cardiomyopathy.