丹参酮ⅡA预防性给药对脑缺血/再灌注损伤炎症反应的影响

目的研究丹参酮ⅡA对大鼠脑缺血/再灌注损伤缺血区白细胞浸润及细胞粘附分子的影响。方法缺血前给予丹参酮ⅡA8,16,32mg·kg-1,灌胃7d,末次给药1h后制备大鼠大脑中动脉阻断短暂局灶性缺血模型。脑缺血2h再灌注24h后,用TTC染色法、伊文思兰法(EB)测定脑梗死范围及血脑屏障的损伤程度。分别用放免、酶免、Westernblot法测定大脑缺血区肿瘤坏死因子-α(TNF-α)、髓过氧化物酶(MPO)的活性、血清白介素-8(IL-8)的含量及血管内皮粘附分子ICAM-1(细胞间粘附分子)、E-selectin(E-选择素)的表达水平。结果丹参酮ⅡA能缩小脑缺血/再灌注后脑梗死体积,减轻神经损伤症状,降低脑内TNF-α、MPO的活性及血清IL-8含量,同时,减少ICAM-1、E-selectin的表达(P<0·05或P<0·01vs模型组)。结论丹参酮ⅡA可通过抑制脑缺血/再灌注过程中炎症介质释放、表达,降低脑缺血/再灌注所致脑损伤。

The Effects of sodium β-aescinate on inflammatory process induced by focal cerebral ischemia -reperfusion in rats

Aim To investigate the protective effects of Tanshinone ⅡA on brain damage following focal cerebral I/R through interfering with inflammatory process. Methods Rats were pretreated with Tanshinone ⅡA at the doses of 8,16,32 mg·kg~ -1 for 7 d and then subjected to cerebral ischemia/reperfusion (I/R) injury induced by a middle cerebral artery occlusion (MCAO). The infarct volume and the neurological deficit were determined by the method of TTC(2,3,5-Triphenyltetrazolium Chloride)staining and Longa′s score. The permeability of the blood brain barrier (blood-brain barrier) was evaluated by measurement of the Evans Blue (EB) content in the brain with spectrophotometer. The serum contents of Interleukin-8 (IL-8), tumor necrosis factor-alapha (TNF-α) and Myeloperoxidase (MPO) were determined by radioimmunoassay (RIA) and ELISA assay. The expressions of ICAM-1、E-selectin were evaluated with Western blot. Results Tanshinone ⅡA reduced infarct volume, ameliorated the neurological deficit and reduced the permeability of blood-brain barrier (P<0.05 or P<0.01 vs vehicle group). Pretreated with Tanshinone ⅡA (16, 32 mg·kg~ -1 ), the concent of IL-8 in serum and TNF-α, MPO activity and the protein expressions of ICAM-1、E-sectin in brain tissue were significantly decreased (P<0.05 or P<0.01 vs sham-operated group). Conclusion These results showed that Tanshinone ⅡA had protective effects on cerebral injury through inhibiting the expression and releasing of the inflammatory mediators after ischemia/reperfusion injury.