Therapeutic effect and mechanism of shikonin on myocardial injury in spontaneous hypertension rats
To understand the therapeutic effect and mechanism of shikonin(Shi)on myocardial injury in spontaneous hyperten-sion rat(SHR),rats were divided into Wistar-Kyoto(WKY)group,SHR model group,SHR+Shi treatment group(Shi 50 mg/[kg·d]),and SHR+losartan(Los)treatment group(Los 10 mg/[kg·d]).The rats were treated for 4 consecutive weeks.The left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),left ventricular end-diastolic diameter(LVEDD),and left ventricular end-systolic diameter(LVESD)were analyzed by echocardiography.H-E staining kit,Sirius scarlet staining kit,and Masson tricolor staining kit were used for histopathological examinations.The myocardial injury(atrial natriuretic peptide[ANP]and lactate dehydrogenase[LDH]),inflammation(IL-17 and TGF-β),and oxidative stress(superoxide dismutase[SOD],catalase[CAT]and malondialdehyde[MDA])parameters of rats in each group were measured.The expressions of Notch2 and Hes1 in myocardial tissue were detected by RT-PCR and Western blot-ting.The results showed that compared to those of the SHR group,the LVEF and LVFS of the SHR+Shi group and SHR+Los group were significantly increased(P＜0.05),while the LVEDD and LVESD were significantly decreased(P＜0.05).The area of myocardial fibrosis in the SHR group was increased,while the areas of myocardial fibrosis in the SHR+Shi group and the SHR+Los group were significantly reduced.Compared to those of the SHR group,the plasma ANP and LDH levels of the SHR+Shi group and the SHR+Los group were significantly reduced(P＜0.05),and the thickness of the thoracic aorta media was significantly reduced(P＜0.05).In addition,the serum SOD and CAT levels were significantly increased(P＜0.05),while the MDA level was significantly decreased(P＜0.05)in the SHR+Shi group and the SHR+Los group.Compared to those of the SHR group,the serum IL-17 levels of the SHR+Shi group and the SHR+Los group were significantly reduced(P＜0.05),while the TGF-β levels were significantly increased(P＜0.05).The mRNA and protein expressions of Notch2 and Hesl in the myocardium of the SHR+Shi group and the SHR+Los group were significantly reduced(P＜0.05)compared to those of the SHR group.This study shows that Shi can alleviate myocardial injury in SHR by inhibiting inflammation and oxidative stress via down-regulation of the Notch2 pathway.
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