叶黄素对大鼠心肌纤维化保护作用

目的 探讨叶黄素（lutein）对异丙肾上腺素（ISO）诱导的大鼠心肌纤维化保护作用及机制。方法 60只大鼠随机分为6组，除对照组外，其余各组大鼠皮下注射ISO 5 mg/kg，连续7 d；造模第2 d，低、中、高剂量叶黄素组大鼠灌胃给予lutein 20、40、80 mg/kg，阳性对照组大鼠给予卡托普利（cap）10 mg/kg，模型组和对照组大鼠给予等量蒸馏水，连续28 d。检测大鼠心脏指数、心电图、运动耐力、心肌组织中羟脯氨酸（HYP）、谷胱甘肽（GSH）、丙二醛（MDA）含量和血清中超氧化物歧化酶（SOD）含量；苏木素-伊红染色（HE）观察大鼠心肌病理学变化。结果 与对照组比较，模型组大鼠运动耐力降低、心指数与左心室指数[分别为（3.73±0.58）、（2.57±0.43） mg/g]增加（P<0.01），心率明显增加，心肌组织中HYP、MDA含量[分别为（0.48±0.07） g/mg、（2.37±0.84） nmol/mgpr]升高（P<0.05），心肌组织中GSH含量、血清中SOD水平[分别为（55.19±2.08） U/mg、（512.17±26.48） U/mL]明显下降（P<0.01），心肌组织间质成分增多，细胞核间距较宽，有大量炎性细胞浸润且纤维组织增生伴心肌萎缩；与模型组比较，高剂量叶黄素组大鼠运动耐力提高、心指数与左心室指数[分别为（3.02±0.28）、（2.09±0.17） mg/g]降低（P<0.01），心肌组织中HYP和丙二醛含量[分别为（0.28±0.06） g/mg、（1.89±0.61） nmol/mgpr]明显降低（P<0.05），心肌组织中GSH含量、血清中SOD水平[分别为（72.70±0.05） U/mg、（571.19±15.58） U/mL]明显升高（P<0.01），心肌组织间质成分略增多，无炎细胞浸润，可见轻度纤维组织增生，无心肌萎缩。结论 叶黄素对异丙肾上腺素所致大鼠心肌纤维化具有一定保护作用，其机制可能与改善大鼠机体抗氧化能力有关。

Protectional effect of lutein on myocardial fibrosis in rats

Objective To explore the protective effect and mechanism of lutein on myocardial fibrosis induced by isopropyl adrenaline in rats.Methods Sixty Wistar rats (half male and half female) were divided into six groups randomly.All the rats were subcutaneously injected with isoproterenol (Iso) at the dose of 5 mg/kg/d for 7 consecutive days to establish myocardial fibrosis model,except for those of the normal control group.At the second day of Iso treatment,the rats of low-,moderate-,and high-lutein groups were gavaged with lutein at the dosages of 20,40,and 80 mg/kg/d and the rats of positive control group were gavaged with captopril (10 mg/kg/d);the rats of model and normal control group were given distilled water of same quantity for 28 consecutive days.By the end of last treatment,the heart weight index of the rats were calculated;Bl-420E+ biological function experiment system was adopted to detect the heart function,electrocardiogram,and exercise endurance of the rats;hydroxyproline (HYP),glutathione (GSH),and malondialdehyde (MDA) in myocardial tissues and serum superoxide dismutase (SOD) were measured;and myocardial pathological changes of the rats were observed with hematoxylin-eosin (HE) staining.Results Compared with the normal control rats,the model rats showed decreased exercise tolerance,significantly increased heart weight index (HWI) (3.73±0.58 mg/g) and left ventricular mass index (LVMI) (2.57±0.43 mg/g) (both P<0.01) and obviously increased heart rate.Significantly increased HYP (0.48±0.07 g/mg),MDA (2.37±0.84 nmol/mgpr),and GSH (55.19±2.08 U/mg)(P<0.05 for all) in myocardial tissues and significantly decreased serum SOD (512.17±26.48 U/ml) (P<0.01) were detected in the model rats.The increase of stroma components,distance enlargement between cell nucleus,large number of inflammatory cells,and fibrous hyperplasia complicated with myocardial hypotrophy were observed in myocardial tissues of the model rats.Compared with the model rats,the rats with high-dose lutein treatment exhibited increased exercise tolerance,significantly decreased HWI (3.02±0.28 mg/g)and LVMI (2.09±0.17 mg/g) (both P<0.01),remarkably decreased myocardial HYP (0.28±0.06 g/mg) and MDA (1.89±0.61 nmol/mgpr) (both P<0.05) and obviously increased myocardial GSH (72.70±0.05 U/mg) and serum SOD (571.19±15.58 U/ml) (both P<0.01).Minor increase of stroma components and fibrous hyperplasia but no inflammatory cell infiltration and hypotrophy were observed in myocardial tissues of the rats with high-dose lutein treatment.Conclusion Lutein presents certain protective effect on isopropyl adrenaline-induced myocardial fibrosis in rats and the mechanism of the effect may be related to the improvement of antioxidant ability.