摘要
Objective: To explore the protective effect and mechanism of Kuntai(KT) Capsule on angiotensin Ⅱ(AngⅡ)-induced hypertension in ovariectomized(OVX) rats. Methods: Fifty-four rats were randomly divided into 6 groups according to a random number table, 9 in each group: control, OVX sham+AngⅡ, OVX, OVX+AngⅡ,OVX+AngⅡ+E2, and OVX+AngⅡ+KT. OVX rats model was constructed by retroperitoneal bilateral ovariectomy.After 4 weeks of pretreatment with KT Capsule [0.8 g/(kg·d) and 17-β-estradiol(E2, 1.2 mg/(kg·d)] respectively,AngⅡ was injected into a micro-osmotic pump with a syringe to establish a hypertensive rat model. Blood pressure of rat tail artery was measured in a wake state of rats using a non-invasive sphygmomanometer.Blood pressure changes were compared between the intervention groups(OVX+AngⅡ+KT, OVX+AngⅡ+E2)and the negative control group(OVX+AngⅡ). Serum malondialdehyde(MDA) level and superoxide dismutase(SOD) activity were detected respectively. The expressions of oxidative stress-related protein superoxide dismutase2(SOD2) and anti-thioredoxin(TRX), autophagy marker protein [beclin1, light chain(LC) 3Ⅱ/Ⅰ ratio and autophagy canonical pathway protein phosphatidylinositol 3-kinase(PI3K)/serine/threonine kinase(AKT)-mammalian target of rapamycin(mTOR)] were evaluated by Western blotting. Results: Compared with the OVX+AngⅡ group, the systolic blood pressure of OVX+AngⅡ+KT group was significantly lowered(P<0.05) but not the diastolic blood pressure. Besides, SOD2 and TRX protein levels in mycardial tissues were significantly reduced in the OVX+AngⅡ+KT group compared with the OVX+AngⅡ group(P<0.05). Oxidative stress serum markers MDA and SOD were down-and up-regulated in the OVX+AngⅡ+KT group, respectively(P<0.05).Compared with OVX+AngⅡ group, the levels of cardiac proteins beclin-1 and LC3Ⅱ/LC3Ⅰ in OVX+AngⅡ+KT group were also up-regulated(P<0.05), and the expression levels of p-PI3K, p-AKT and mTOR protein were down-regulated(P<0.05). Conclusion: KT could protect blood pressure of AngⅡ-induced OVX rats by inhibiting oxidative stress and up-regulating protective autophagy.
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