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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 effect of quercetin on hepatic cirrhosis-induced myocardial damage and its mechanism. To investigate the inhibitory effect of quercetin on the further development of hepatic fibrosis and its myocardial damage induced by praziquantel and its mechanism. Methods 80 mice were randomly divided into 4 groups. A, B, C mice infected with Schistosoma japonicum cercariae, D mice as control group. After 8 weeks of infection of cercariae in groups A, B and C, the mice in group A were treated with praziquantel 500 mg / kg for 2 days. The mice in group B were treated with praziquantel 500 mg / kg for 2 days, followed by quercetin 30 mg / kg for 8 weeks; group C mice were not treated (model group). Group D mice were normally fed. At the end of the 16th week, the mice were sacrificed and the liver and myocardium were taken for histopathology. The pathological changes of liver and myocardium and ultrastructure of myocardial tissue were observed by HE staining, transmission electron microscopy, RT-PCR and immunohistochemistry. The expression of c-fos mRNA, c-jun mRNA, transforming growth factor β1 (TGF-β1), type I and type Ⅲ collagen in myocardium were analyzed. Results The model group, praziquantel group, praziquantel + quercetin combined treatment group mice with varying degrees of myocardial injury. The expression of c-jun mRNA, TGF-β1, type I and type III collagen in myocardium was significantly lower than that in the model group after praziquantel treatment, and the level of c-fos mRNA, c- The treatment with verapin could further reduce the degree of hepatic fibrosis and myocardial injury and decrease the expression of c-fos mRNA, c-jun mRNA, TGF-β1, type I and type III collagen in myocardium, but its expression was still higher than that of the control group. Conclusions In advanced stage, cirrhosis of schistosomiasis can induce myocardial overproduction of myocardial remodeling by stimulating immediate early gene expression in myocardium. Anti-fibrosis treatment can reduce myocardial remodeling. Quercetin can protect myocardium by reducing the degree of hepatic fibrosis, inhibiting early gene expression in myocardium and decreasing the level of TGF-β1 in myocardium.