Effects of Astragaloside Ⅳ on Myocardial Fibrosis and Th17 Cell Differentiation in Rats with Adriamycin Induced Dilated Cardiomyopathy
Objective:To investigate the effects of astragaloside Ⅳ(AS-Ⅳ)on myocardial fibrosis and Th17 cell differentiation in rats with adriamycin induced dilated cardiomyopathy(DCM).Methods:The model of DCM rats were established by intraperitoneal in-jection of adriamycin at the dose of 2.5 mg/kg,and the DCM rats were divided into model group,low AS-Ⅳ group,medium AS-Ⅳgroup and high AS-Ⅳ group,with 10 rats in each group.In addition,10 healthy SD rats were set as control group.The rats in low AS-Ⅳgroup,medium AS-Ⅳ group and high AS-Ⅳ group were given AS-Ⅳ at doses of 20 mg/kg,40 mg/kg and 80 mg/kg once a day for a to-tal of 6 weeks.Rats in control group and model group were simultaneously given equal volume normal saline intragastric administration.After administration,the cardiac function index included left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic di-ameter(LVEDD)and left ventricular ejection fraction(LVEF)were detected by ultrasound.The pathological changes of myocardial tis-sue were detected by Hematoxylin-eosin(HE)and Masson staining.The level of Th17 cells in spleen tissue of rats were detected by flow cytometry.The levels of IL-17,IL-21 and TNF-α in serum were detected by ELISA.The mRNA expression levels of RORγt and FoxP3 in rat myocardial tissue were detected by qRT-PCR,and the protein expressions of α-SMA,collagen I,TGF-β1,RORγt and FoxP3 in rat myocardial tissue were detected by Western blot.Results:The results of HE and Masson staining showed that inflammatory cell infiltra tion and cell hypertrophy occurred in the myocardium of the model group,and blue-stained collagen deposition increased in the intersti-tial tissue.Compared with model group,inflammatory cell infiltration and cell hypertrophy in myocardium of rats in low AS-Ⅳ group,medium AS-Ⅳ group and high AS-Ⅳ group were gradually relieved,and the amount of collagen deposition was reduced.Compared with control group,LVESD and LVEDD indexes of model group were increased(P＜0.05),while LVEF indexes were decreased(P＜0.05).The levels of α-SMA,collagen Ⅰ,TGF-β1 and RORγt in myocardial tissue were increased(P＜0.05),while FoxP3 level was decreased(P＜0.05).The proportion of Th17 cells in spleen tissue was increased(P＜0.05).The levels of IL-17,IL-21 and TNF-α in serum were in-creased(P＜0.05).Compared with control group,LVESD and LVEDD indexes of model group were decreased(P＜0.05),while LVEF in-dexes were increased(P＜0.05).The levels of α-SMA,collagen Ⅰ,TGF-β1 and RORγt in myocardial tissue were decreased(P＜0.05),while FoxP3 level was increased(P＜0.05).The proportion of Th17 cells in spleen tissue was decreased(P＜0.05).The levels of IL-17,IL-21 and TNF-α in serum were decreased(P＜0.05).Conclusion:AS-Ⅳ showed good therapeutic effect on DCM rats induced by adri-amycin,the mechanism of which may be related to anti-myocardial fibrosis and inhibition of Th17 cell differentiation.
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