目的研究血吸虫肝硬化致心肌损害作用及其机制,探讨槲皮素对吡喹酮杀虫治疗后血吸虫肝纤维化进一步发展及其致心肌损伤的抑制作用及其机制。方法80只小鼠随机分为4组。A、B、C 3组小鼠感染日本血吸虫尾蚴,D组小鼠为对照组。A、B、C 3组小鼠感染尾蚴8周后,A组小鼠以吡喹酮500 mg/kg治疗2 d;B组小鼠以吡喹酮500 mg/kg治疗2d后继以槲皮素30 mg/kg治疗8周;C组小鼠不作任何治疗(模型组)。D组小鼠正常饲养。第16周末处死小鼠,留取肝脏、心肌组织,应用HE染色法、透射电镜、RT-PCR及免疫组化染色法,观察各组小鼠肝脏、心肌组织病理及心肌组织超微结构改变,分析心肌组织中c-fos mRNA、c-jun mRNA、转化生长因子β1(TGF-β1)、Ⅰ和Ⅲ型胶原的表达变化。结果模型组、吡喹酮组、吡喹酮+槲皮素联合治疗组小鼠均存在不同程度心肌损伤。吡喹酮治疗后肝纤维化及心肌损伤程度减轻,心肌组织中c-fos mRNA、c-jun mRNA、TGF-β1、Ⅰ和Ⅲ型胶原表达均明显低于模型组,杀虫治疗后继以槲皮素治疗,可进一步减轻肝纤维化及心肌损伤程度,降低心肌组织中c-fos mRNA、c-jun mRNA、TGF-β1、Ⅰ和Ⅲ型胶原表达,但其表达仍高于对照组。结论晚期血吸虫病肝硬化可通过刺激心肌即早基因表达、促使TGF-β1过度产生而致心肌重塑。抗肝纤维化治疗可减轻心肌重塑程度。槲皮素可通过减轻肝纤维化程度、抑制心肌即早基因表达,降低心肌TGF-β1水平而发挥保护心肌作用。

Objective To study the effects and mechanisms of myocardial injury in schistosome-infected mice.To investigate the effects and mechanisms of quercetin on myocardial injury due to the development of hepatic fibrosis after being treated by Praziquantel.Methods Eighty mice were divided into four groups:group A,group B,group C,and group D.Group A，group B, and group C were infected with Schistosoma japonicum cercariae.After 8 weeks，group A was treated with Praziquantel 500 mg/kg for 2d, group B was treated with quercetin 30 mg/(kg·d) for 8 weeks after being treated with Praziquantel 500 mg/kg for 2d. Group C was taken as experimental control without any treatment.Group D was taken as normal control.At the week 16，all mice were sacrificed and a part of liver tissue and myocardium tissue were preserved.HE Staining, electric microscope，RT-PCR，and immunohistochemical technique were applied to observing the changes of hepatic and cardiac histopathology, myocardial ultramicrostructure，the expression of myocardial c-fos,c-jun mRNA，and the contents of myocardial transforming growth factor-β1(TGF-β1),type Ⅰ and type Ⅲ collagen in mice infected with S.iaponicum before and after treatmenu.Results There was different degree of myocardial injury among three groups of experimental control,Praziquantel treatment，Praziquantel combined with quercetin treatment.Praziquantel treatment relieved the degree of hepatic fibrosis and myocardial injury.The content of myocardial c-fos mRNA，c-jun mRNA，TGF-β1，type j and type collagen were obviously reduced compared to the experimental control.When Praziquantel treatment combined with quercetin, the degree of hepatic fibrosis and myocardial injury were further relieved.Although the content of myocardial c-fos mRNA，c-jun mRNA，TGF-β1，type Ⅰ and thype Ⅲ collagen were still higher than those in normal control，those were reduced significantly compared to the group treated with Praziquantel.ConclusionHepatic cirrhosis due to advanced schistosomiasis may lead to cardiac remodeling by stimulating the expression of immediate early gene and promoting the overexpression of TGF-β1 in myocardium. Anti-fibrosis therapy can reduce the degree of cardiac remodeling. Quercetin may protect myocardium through reducing the degree of hepatic fibrosis and inhibiting the expression of immediate early gene, which could decrease the level of myocardial TGF-β1.