The Preliminary Study Of Protective Effect Of Dihydrotanshinone ? On Experimental Atherosclerosis

Objective: To investigate the effect and mechanism of dihydrotanshinone?(DHT),a lipophilic constituent of traditional Chinese medicine Salvia miltiorrhiza Bunge,on experimental atherosclerosis(AS).Methods: After 3 weeks of adaptive feeding in the SPF environment,the 6-weeks-old male Apo E-knockout mice(Apo E-/-)were randomly divided into model group,DHT low dose group(10 mg / kg)and DHT high dose group(25 mg / kg).The C57 BL / 6J mice with the same gene background and age were set as control group,divided into 4 groups in total.DHT was formulated with 1% Tween-80.After one week of intragastric administration,AS animal model was established by feeding Apo E-/-mice with high cholesterol diet(HCD),and C57 BL / 6J mice were fed with standard diet(SD).This study was administered by intragastric administration once a day for 12 weeks.Normal and model groups were given an equal amount of 1% Tween-80 as a control.After 12 weeks,Mice were sacrificed and the fasting blood glucose(FBG),body weight and abdominal girth were measured.The serum levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C),high density lipoprotein(HDL-C),superoxide dismutase(SOD),glutathione(GSH)and malondialdehyde(MDA)were detected.The aorta were collected and were stained with Oil Red O and hematoxylin and eosin(HE).Furthermore,the expression of lectin-like oxidized low density lipoprotein receptor-1(LOX-1),NADPH oxidase 4(NOX4),transcription factor nuclear factor-kappa B p65(NF-?B p65)in aorta was determined by immunohistochemistry and immunofluorescence.Results: Compared with the AS model,DHT administration showed no effect on either FBG,body weight,or abdominal girth but decreased the serum levels of TC,TG and LDL-C at 25mg/kg dosage.Meanwhile,the serum levels of SOD and GSH in serum were significantly increased and the level of MDA was significantly decreased.Furthermore,Oil red O and HE staining results revealed that the aortic walls were smooth in the control group,which were thickened in the model group with vacuolization of orange-red lipid infiltration and foam cell necrosis.These abnormalities were partially improved by DHT treatment.In addition,immunohistochemistry and immunofluorescence showed that DHT significantly reduced the expression of NOX4,NF-?B p65 and LOX-1 in the arterial walls.Conclusion: In summary,these data suggested that DHT,a natural product,possesses inhibitory effect on experimental AS.The underlying mechanisms may involve to the reduction of lipid level and oxidative stress level in serum.At the same time,DHT inhibit the expression of NOX4,NF-?B p65 and LOX-1 in atherosclerotic lesions.