二苯乙烯苷抑制异丙肾上腺素诱导小鼠心肌纤维化及其机制研究  

2,3,4',5-tetrahydroxystilbene-2-O-β-D-glycoside inhibits isoproterenol-induced myocardial fibrosis in mice and its possible mechanisms

作　　者：曾翼[1] 王霏[2] 许晓乐[1] 

机构地区：[1]南通大学药学院药理学教研室江苏省炎症与分子药靶重点实验室,江苏南通226001 [2]南通大学附属医院心胸外科实验室,江苏南通226001

出　　处：《中国药理学通报》2015年第10期1388-1393,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金青年基金资助项目(No 81200079);南通大学自然科学项目(No 14Z021);南通大学研究生科技创新计划资助项目(YKC13065);江苏高校优势学科建设工程项目

摘　　要：目的观察二苯乙烯苷(2,3,4',5-tetrahydroxystilbene-2-O-β-D glucoside,TSG)对异丙肾上腺素(isoproterenol,ISO)诱导的小鼠心肌纤维化的作用及其相关机制。方法采用连续皮下注射异丙肾上腺素14 d诱导小鼠心肌纤维化模型,同时以TSG(120、60、30 mg·kg-1)和阳性对照卡托普利(40 mg·kg-1)灌胃给药。末次给药12 h后,取心室肌进行苏木精伊红(hematoxylineosin,HE)染色和Masson染色,观察纤维化的程度;测定心肌羟脯氨酸(hydroxyproline,HYP)含量;检测心肌组织中Ⅰ、Ⅲ型胶原,转化生长因子-β1(transforming growth factor-β1,TGF-β1)的蛋白表达水平;测定心肌组织中超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase-Px,GSH-Px)活性。结果与正常对照组相比,模型组心肌出现明显纤维化,心肌组织HYP水平明显增高,Ⅰ、Ⅲ型胶原蛋白表达明显增加。与模型组相比,TSG能减轻心肌纤维化程度,降低心肌组织HYP水平及心肌组织中Ⅰ、Ⅲ型胶原蛋白表达。同时,TSG降低心肌组织中TGF-β1的蛋白表达,且能升高损伤心肌组织中SOD和GSH-Px的活性。结论 TSG可抑制ISO诱导的小鼠心肌纤维化,其机制可能与调节TGF-β1蛋白表达及其抗氧化有关。Aim To study the effects of 2 ,3 ,4 ’ ,5-tet-rahydroxystilbene-2-O-β-D glucoside ( TSG ) on myo-cardial fibrosis ( MF) induced by isoproterenol ( ISO) in mice and its possible mechanism. Methods MF in mice was induced by subcutaneous injection of isoprot-erenol for 14 days. TSG (30,60,120 mg·kg-1 ) and captopril ( 40 mg · kg-1 ) were then administered by gavage to mice. The experiment was stopped 12 h after the last administration of the drugs. Hematoxylin-eosin ( HE) and Masson staining were used to estimate the extent of MF. Level of hydroxyproline in myocardial tissues was measured. Protein expressions of collagenⅠ, collagen Ⅲ and transforming growth factor-β1 (TGF-β1) in myocardial tissues were measured. Lev-els of superoxide dismutase ( SOD ) and glutathione peroxidase ( GSH-Px ) were determined. Results Compared with control mice, the level of hydroxypro-line in myocardial tissues was significantly increased in isoproterenol treated mice. Histological sections of iso-proterenol-treated hearts showed extensive myocardial fibrosis. And protein expressions of collagenⅠand col-lagen Ⅲwere markedly increased in isoproterenol trea-ted mice. However, therapy with TSG decreased the level of hydroxyproline in myocardial tissues, ameliora-ted the degree of myocardial fibrosis, and reduced the collagen expressions induced by isoproterenol adminis-tration. Moreover, treatment with TSG decreased TGF-β1 protein expression and elevated the myocardial SOD and GSH-Px activity. Conclusion TSG can inhibit MF formation induced by ISO in mice which might be due to regulating TGF-β1 protein expression and its an-tioxidant effect.

关 键 词：二苯乙烯苷 异丙肾上腺素 心肌纤维化 胶原 转化生长因子-Β1 氧化应激 

分 类 号：R-332[医药卫生] R322.11