白藜芦醇对小鼠慢性病毒性心肌炎心肌纤维化的干预作用

Effect of resveratrol on myocardial fibrosis in mice with chronic viral myocarditis

摘要:

目的：目前研究认为白藜芦醇能改善病毒性心肌炎(VMC)急性期小鼠心功能及心肌损伤，在体外也具有抑制小鼠心肌纤维化的作用，但在VMC慢性期小鼠模型上，是否具有抑制心肌纤维化的作用尚未见报道。该研究旨在探讨白藜芦醇对VMC慢性期心肌纤维化干预的效果，从而为临床治疗VMC提供一定的实验依据。方法：柯萨奇病毒B3(CVB3)感染BALA/c小鼠建立VMC慢性期动物模型，30 d后将小鼠随机分为VMC模型对照组, 白藜芦醇小剂量组(10 mg/kg)，中剂量组(100 mg/kg)及大剂量组(1 000 mg/kg)，并设正常对照。30 d后，处死小鼠摘取心脏及提取血液，酶联免疫吸附法测各组小鼠胶原前肽(PINP，PICP及PIIINP)的血清浓度，心脏切片行苏木精-伊红染色及苦味酸天狼猩红胶原组织化学染色并计算胶原容积积分。结果：白藜芦醇大剂量组（0.74±0.19）及中剂量组（1.07±0.12）心肌胶原容积积分较小剂量组(2.17±0.19)和VMC模型对照组(2.33±0.18)明显减少，差异有显著性(P<0.05)。 大剂量组和中剂量组比较差异无显著性，小剂量组和VMC模型对照组比较差异无显著性。与VMC模型对照组比较，白藜芦醇高剂量组及中剂量组血清中Ⅰ型前胶原羧基端前肽（PICP）及Ⅲ型前胶原氨基端前肽（PIIICP）含量明显减少，差异有显著性（P<0.05），而Ⅰ型前胶原氨基端前肽（PINP）含量明显增多，差异亦有显著性（P<0.05）。结论：VMC慢性期小鼠模型上，白藜芦醇能抑制VMC心肌胶原的增生，具有抗心肌纤维化的作用。［中国当代儿科杂志，2009，11（4）：291-295］

Abstract:

OBJECTIVE: Some research has shown that resveratrol can ameliorate myocardial injury and improve cardiac function in mice with acute viral myocarditis (VMC), and can inhibit cardiac fibroblast proliferation and myofibroblast differentiation in vitro. This study was designed to investigate whether resveratrol has similar effects in the mouse model of chronic VMC. METHODS: One hundred mice were inoculated with 0.3 mL of Coxsackievirus B3 1×106 TCID50. Thirty days later, the survivors (n=62) were used as a model of chronic VMC, and were randomly assigned to 4 groups: untreated VMC, and low- (10 mg/kg), middle- (100 mg/kg) and high-dose (1 000 mg/kg) resveratrol-treated VMC (once daily, for 30 days). Ten mice which received neither Coxsackievirus B3 nor resveratrol treatment served as the control group. After 30 days of resveratrol treatment, the mice were sacrificed. Serum concentrations of collagenous pre-peptides (PINP, PICP and PIIINP) were assessed using ELISA. Hematoxylin-eosin staining, picrosirius red staining and circularly polarized light were used to examine the histochemistry of myocardial collagen. RESULTS: The myocardial collagen volume fraction in the high-dose (0.74±0.19) and the middle-dose (1.07±0.12 ) resveratrol-treated VMC groups was significantly lower than that in the untreated VMC (2.33±0.18) and the low-dose resveratrol-treated VMC (2.17±0.19) groups (P<0.05). Compared with the untreated VMC group, serum concentrations of PICP and PIIINP in the high-dose and the middle-dose resveratrol-treated VMC groups were significantly reduced (P<0.05), while PINP concentrations increased significantly (P<0.05). CONCLUSIONS: Resveratrol can inhibit hyperplasia of myocardial collagen in the mouse model of chronic VMC, acting as an effective anti-fibrotic agent in the myocardium.［Chin J Contemp Pediatr, 2009, 11 (4):291-295］