Zhou L, Bondy S C, Jian L, Wen P, Yang F, Luo H, Li W, Zhou Jun
Department of Pathology, the Xiang-ya Hospital, Changsha 410008, China.
Center for Occupational and Environmental Health, Department of Medicine, University of California, Irvine, CA 92697-1830, USA.
Neuroscience. 2015 Mar 12;288:105-11. doi: 10.1016/j.neuroscience.2014.12.028. Epub 2015 Jan 6.
Tanshinone IIA (TSA) is a lipid soluble agent derived from the root of Salvia miltiorrhiza (Danshen). This plant is a traditional Chinese herb, which has been used widely in China especially for enhancing circulation. However mechanisms underlying its efficacy remain poorly understood. The present study was designed to illuminate events that may underlie the apparently neuroprotective effects of TSA following ischemic insult. Adult Sprague-Dawley rats were subjected to transient focal cerebral ischemia by use of a middle cerebral artery occlusion model. They were then randomly divided into a sham-operated control group, and cerebral ischemia/reperfusion groups receiving a two-hour occlusion. Further subsets of groups received the same durations of occlusion or were sham-operated but then received daily i.p. injections of high or low doses of TSA, for seven or 15days. Hematoxylin and eosin staining revealed lesions in the entorhinal cortex of both rats subject to ischemia and to a lesser extent to those receiving TSA after surgery. Levels of glial fibrillary acidic protein (GFAP), caspase-3 and caspase-8, were quantified by both immunohistochemistry and Western blotting. TSA treatment after middle cerebral artery occlusion, markedly reduced infarct size, and reduced the expression of caspase-3 and caspase-8. These changes were considered protective and were generally proportional to the dose of TSA used. These results suggest that TSA may effect neuroprotection by way of reduction of the extent of cell inflammation and death within affected regions.
丹参酮IIA（TSA）是一种从丹参根部提取的脂溶性药物。丹参是一种传统的中草药，在中国广泛用于促进血液循环。然而，其疗效的潜在机制仍知之甚少。本研究旨在阐明TSA在缺血性损伤后明显的神经保护作用可能涉及的机制。成年Sprague-Dawley大鼠通过大脑中动脉闭塞模型进行短暂性局灶性脑缺血。然后将它们随机分为假手术对照组和接受两小时闭塞的脑缺血/再灌注组。进一步的亚组接受相同时间的闭塞或进行假手术，但随后每天腹腔注射高剂量或低剂量的TSA，持续7天或15天。苏木精和伊红染色显示，缺血大鼠的内嗅皮质有损伤，术后接受TSA治疗的大鼠损伤程度较轻。通过免疫组织化学和蛋白质印迹法对胶质纤维酸性蛋白（GFAP）、半胱天冬酶-3和半胱天冬酶-8的水平进行定量。大脑中动脉闭塞后给予TSA治疗，可显著减小梗死面积，并降低半胱天冬酶-3和半胱天冬酶-8的表达。这些变化被认为具有保护作用，且通常与所用TSA的剂量成正比。这些结果表明，TSA可能通过减少受影响区域内细胞炎症和死亡的程度来发挥神经保护作用。
