摘要
目的:探索木樨草素-7-二葡萄糖醛酸苷(luteolin-7-diglucuronide,L7DG)通过口服干预,抗异丙肾上腺素(isoproterenol,ISO)所诱导心肌损伤的作用,为进一步临床应用提供有力的实验依据。方法:以10 mg·kg~(-1)的ISO持续腹腔注射5d,模拟C57BL/6雄性小鼠心肌损伤模型。于每次ISO腹腔注射前30 min分别给予L7DG两种剂量口服干预,即L7DG低剂量(120 mg·kg~(-1))与L7DG高剂量(240 mg·kg~(-1))。分别通过HE染色及Masson's染色,评价L7DG抗ISO所诱导的心肌损伤、心肌肥大以及纤维化的作用。结果:HE染色结果提示,与模型组相比,L7DG高剂量组与低剂量组炎性细胞浸润均显著降低(P <0. 05),此外,L7DG高剂量组与低剂量组均未见ISO诱导的左心室扩张性改变; Masson's染色结果提示,与模型组相比,L7DG高剂量组与低剂量组心肌纤维化沉积均显著降低(P <0. 05);与正常组相比,模型组左心室心肌横截面积显著增大(P <0. 05);而与模型组相比,L7DG高剂量组与低剂量组左心室心肌细胞横截面积均显著降低(P <0. 05)。结论:口服L7DG可显著减低ISO所诱导小鼠心肌损伤、纤维化、心肌细胞肥大的程度并改善左心室扩张性改变,这将为L7DG进一步应用于相关心血管疾病的治疗提供有力的临床支撑。
Objective: To explore the effect of Luteolin-7-diglucuronide( L7DG) on myocardial injury induced by isoproterenol( ISO) through oral intervention,and to provide a powerful experimental basis for further clinical application. Methods: The model of myocardial injury in C57BL/6 male mice was simulated by intraperitoneal injection of isoproterenol( 10 mg·kg~(-1)) for 5 days.Luteolin-7-diglucuronide was given orally at two doses 30 minutes before each intraperitoneal injection of isoproterenol,which is low doses of luteolin-7-diglucuronide( 120 mg·kg~(-1)) and high doses of luteolin-7-diglucuronide( 240 mg·kg~(-1)). HE staining and Masson's staining were used to evaluate the anti-isoproterenol-induced myocardial injury,hypertrophy and fibrosis effects of luteolin-7-diglucuronide. Results: HE staining results showed that compared with model group,luteolin-7-diglucuronide high-dose group and low-dose group significantly decreased inflammatory cell infiltration( P < 0. 05). In addition,no anti-isoproterenol-induced left ventricular dilatation was observed in the high-dose group and the low-dose group of luteolin-7-diglucuronide. Masson's staining results showed that compared with model group,luteolin-7-diglucuronide high-dose group and low-dose group significantly decreased myocardial fibrosis deposition( P < 0. 05). Compared with the normal group,the cross-sectional area of left ventricular myocardium in the model group increased significantly( P < 0. 05),while compared with the model group,the cross-sectional area of left ventricular myocardium in the high-dose luteolin-7-diglucuronide group and the low-dose group decreased significantly( P <0. 05). Conclusion: Oral administration of luteolin-7-diglucuronide can significantly reduce the degree of anti-isoproterenol-induced myocardial injury,fibrosis and cardiomyocyte hypertrophy in mice and improve left ventricular dilatation,which will provide strong clinical support for further application of luteolin-7-diglucuronide in the treatment of related cardiovascular diseases.
引文
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