Astragaloside Ⅳ ameliorates myocardial injury in angiotensin Ⅱ induced hypertension rat model by regulating chloride intracellular channel protein 4/ADP-ribosylation factor 6 signal pathway
Objective To explore the cardioprotective effect and mechanism of astragaloside Ⅳ(AS-Ⅳ)on angio-tensin Ⅱ(Ang Ⅱ)induced hypertension rat model.Methods Sixty Sprague-Dawley(SD)rats were randomly di-vided into 6 groups,with 10 rats in each group:control group,model group,AS-Ⅳ low dose group(10 mg/kg),AS-Ⅳ medium dose group(20 mg/kg),AS-Ⅳ high dose group(50 mg/kg)and specific inhibitor of ADP-ribosyla-tion factor 6(Arf6)(NAV-2729)group.Rats were treated with different drugs or doses after Ang Ⅱ-induced hyper-tensive myocardial injury models were established.The left ventricular end-diastolic diameter,cardiac ejection frac-tion and fractional shortening,myocardial pathological injury,myocardial apoptosis and the expression of related ap-optotic proteins Bcl-2(B-cell lymphoma-2)and Bax(Bcl-2 associated X)in each group were observed after 2 weeks.The other 30 SD rats were randomly divided into three groups,with 10 rats in each group:chloride intracellular channel protein 4(CLIC4)overexpression combined with AS-Ⅳ group,adenovirus negative control combined with AS-Ⅳ group and adenovirus negative control group.The rats were injected with corresponding adenovirus by tail vein and then Ang Ⅱ-induced hypertensive model was eatablished.The end-diastolic internal diameter of the left ventricle,left ventricular ejection fraction,fractional shortening,myocardial pathological damage,and myocardial apoptosis were observed after 2 weeks.Results Compared with the model group,the middle dose and high dose of AS-Ⅳ could improve the cardiac function and myocardial structure of Ang Ⅱ-induced hypertensive myocardial injury model rats,promote the expression of anti-apoptotic protein Bcl-2(0.36±0.01 vs 0.22±0.02,0.78±0.01 vs 0.22±0.02;both P＜0.05)and inhibit the expression of Bax(1.51±0.02 vs 2.13±0.03,1.22±0.01 vs 2.13± 0.03;both P＜0.05).AS-Ⅳ exerted myocardial protective effect by inhibiting the expression of CLIC4/Arf6 pro-tein,and overexpression of CLIC4 attenuated this protective effect.Conclusion AS-Ⅳ can ameliorate myocardial inju-ry in Ang Ⅱ-induced hypertension rat model,possibly through inhibiting CLIC4/Arf6 signaling pathway.
astragaloside Ⅳchloride intracellular channel protein 4/ADP-ribosylation factor 6angiotensin Ⅱhypertensionmyocardial injury
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