Department of Cardiology, Union Hospital of Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China; Department of Cardiology, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an, 710061, Shanxi Province, China.
Fundam Clin Pharmacol. 2014 Feb;28(1):42-52. doi: 10.1111/j.1472-8206.2012.01074.x. Epub 2012 Sep 18.
Atorvastatin is not only an antilipemic but also used as an anti-inflammatory medicine in heart disease. Our working hypothesis was that atorvastatin preconditioning could improve the forward blood flow in the no-reflow rats associated with inflammation. We investigated that two doses of atorvastatin preconditioning (20 and 5 mg/kg/day) could alleviate deterioration of early cardiac diastolic function in rats with inflammation detected by echocardiography and haemodynamics. This benefit was obtained from the effect of atorvastatin preconditioning on improving forward blood flow and preserving the infarct cardiomyocytes, which was estimated by Thioflavin S and TTC staining in rats with myocardial ischemia/reperfusion. Subsequently, the improving of forward blood flow was ascribed to reduction of microthrombus in microvascular and myocardial fibrosis observed by MSB and Masson's trichrome staining with atorvastatin preconditioning. Ultimately, we found that atorvastatin preconditioning could reduce inflammation factor, such as tumor necrosis factor-α and fibrinogen-like protein 2, both in myocardial and in mononuclear cells, which probably attribute to microcirculation dysfunction in no-reflow rats detected by immunohistochemistry staining, western blot, and ELISA detection, respectively. In conclusion, atorvastatin preconditioning could alleviate deterioration of early cardiac diastolic function and improve the forward blood flow in the no-reflow rats attributing to reduction of TNF-α and fgl-2 expression.
阿托伐他汀不仅具有降脂作用，还可用作心脏病的抗炎药物。我们的工作假设是，阿托伐他汀预处理可以改善无复流大鼠的前向血流，同时减轻炎症反应。我们通过超声心动图和血流动力学检测发现，两种剂量的阿托伐他汀预处理（20 和 5mg/kg/天）可以减轻炎症大鼠早期舒张功能的恶化。这种益处来自阿托伐他汀预处理对改善前向血流和保护梗死心肌细胞的作用，通过心肌缺血/再灌注大鼠的硫黄素 S 和 TTC 染色进行评估。随后，通过 MSB 和 Masson 三色染色观察到阿托伐他汀预处理减少了微血管和心肌纤维化中的微血栓，从而改善了前向血流。最终，我们发现阿托伐他汀预处理可以降低心肌和单核细胞中的炎症因子，如肿瘤坏死因子-α和纤维蛋白原样蛋白 2，这可能归因于无复流大鼠的微循环功能障碍，通过免疫组化染色、Western blot 和 ELISA 检测分别检测到。总之，阿托伐他汀预处理可以减轻无复流大鼠早期舒张功能恶化，并改善其前向血流，这归因于 TNF-α和 fgl-2 表达的减少。
