Effects and Mechanisms of Baicalin on Angiotensin Ⅱ-Induced Pathological Left Ventricular Remodeling
Objective The current study aims to investigate the protective effect and mechanisms of baicalin on pathological left ventricular remodeling.Methods Angiotensin Ⅱ(Ang Ⅱ)infusion mouse model was adopted to evaluate the impact of baicalin on pathological left ventricular remodeling in vivo.C57BL/6J mice were randomly allocated to 5 experimental groups,including sham controls,model group(Ang Ⅱ-infusion controls),as well as low-,medium-,and high-dose baicalin treatment groups.Except for the sham controls,C57/BL6 mice were subjected to AngⅡ infusion for 2 weeks.The mice from the baicalin treatment groups received baicalin via gavage at the indicated doses for 2 weeks.The blood pressure,body weight,heart weight and tibia length were measured at the end of the indicated treatments.Immunohistochemistry of wheat germ agglutinin(WGA)was performed to examine the cross-sectional area of cardiomyocytes.Immunohistochemistry was also performed to assess the expression of atrial natriuretic peptide(ANP)in cardiomyocytes.Hematoxylin/eosin(HE)staining and Masson's trichrome staining were performed to evaluate the cardiac pathologies.In vitro experiments were as follows.Ang Ⅱ was adopted to induce cardiomyocyte hypertrophy in H9C2 cells in order to determine if baicalin is able to directly suppress cardiomyocyte hypertrophy.H9C2 cells were divided into vehicle control group(VC group),model group(Ang Ⅱ group)and baicalin group(Bai group).The morphology and size of cardiomyocytes were examined by rhodamine phalloidin staining.The intracellular level of ANP was analyze by immunofluorescence staining.Mitochondrial superoxide(Mito-SOX)was assessed to evaluate oxidative stress.The mitochondrial membrane potential(ΔΨm)was analyzed by JC-1 staining.The opening of mitochondrial permeability transition pore(mPTP)was evaluated by calcein acetyl methyl ester(Calcein AM)staining.Results The in vivo findings:Baicalin significantly antagonized Ang Ⅱ-induced elevation of systolic blood pressure(P<0.05)when administered at the medium and high doses.Meanwhile,baicalin treatment resulted in lower ratios of heart weight to tibia length(HW/TL)and heart weight to body weight(HW/BW)in Ang Ⅱ-infused mice.Baicalin treatment mitigated cardiomyocyte hypertrophy(P<0.05)and lowered the level of cardiomyocyte ANP(P<0.05)in Ang Ⅱ-infused mice.Furthermore,baicalin treatment significantly alleviated cardiac inflammation and fibrosis in Ang Ⅱ-infused mice(P<0.05).In vitro findings:Baicalin suppressed Ang Ⅱ-stimulated enlargement of cardiomyocytes and elevation of the intracellular ANP in H9C2 cells.Moreover,baicalin alleviated Ang Ⅱ-induced mitochondrial oxidative stress,mitochondrial ΔΨm impairment and mPTP opening(P<0.05).Conclusion Our current findings demonstrate that baicalin is effective at mitigating Ang Ⅱ-mediated left ventricular pathological remodeling.Baicalin is pharmacologically active at antagonizing Ang Ⅱ-induced hypertrophic responses and mitochondrial dysfunction in cardiomyocytes,which may in part account for its therapeutic effects against pathological left ventricular remodeling.
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