Li Qin, Han Li-pei, Li Ze-hui, Zhang Jun-tian, Tang Min-ke
Beijing University of Chinese Medicine, Beijing 100102, China.
Yao Xue Xue Bao. 2010 Dec;45(12):1485-90.
The aim of the study is to investigate the effect of salvianolic acid B (SalB) on blood-brain barrier (BBB) in rats after cerebral ischemia-reperfusion, and to illustrate its possible mechanisms. Cerebral ischemia-reperfusion was induced by middle cerebral artery occlusion in rats. The break-down of BBB was indicated by extravasations of immunoglobulin (IgG) monitored with immunohistochemistry. The expression of MMP-9 and NOS2 in the brain was determined by immunohistochemistry, and the expression of p-p38 and p-ERK1/2 was detected by Western blotting. It was shown that on day 2 after ischemia-reperfusion the IgG accumulated around the vascular boundary zone, suggesting the break-down of BBB, and the expression of MMP-9 and NOS2 up-regulated at the same time. The result of Western blotting suggested that the expression of p-p38 and p-ERK1/2 increased. On day 7 after ischemia-reperfusion the. expression of MMP-9 and NOS2 was about the same level as day 2, the expression of p-p38 was higher than that on day 2 and the expression of p-ERK1/2 was slightly lower than that on day 2. SalB (1 and 10 mg x kg(-1)) significantly alleviated the extravasations of immunoglobulin induced by cerebral ischemia-reperfusion (P < 0.05). On day 2 and day 7 SalB attenuated the expression of MMP-9 and NOS2 (P < 0.05). SalB (10 mg x kg(-1)) reduced the expression of p-p38 and p-ERK1/2 apparently on day 2 and 7 after ischemia-reperfusion (P < 0.05). SalB (1 mg x kg(-1)) inhibited the expression of p-p38 on day 7 after ischemia-reperfusion (P < 0.05). The results indicate that SalB protects blood-brain barrier in rats after cerebral ischemia-reperfusion by inhibiting the MAPK pathway.
本研究旨在探讨丹酚酸B（SalB）对大鼠脑缺血再灌注后血脑屏障（BBB）的影响，并阐明其可能的机制。采用大鼠大脑中动脉闭塞法诱导脑缺血再灌注。通过免疫组化监测免疫球蛋白（IgG）外渗来指示血脑屏障的破坏。采用免疫组化法测定大脑中MMP-9和NOS2的表达，采用蛋白质印迹法检测p-p38和p-ERK1/2的表达。结果显示，缺血再灌注后第2天，IgG在血管边界区周围积聚，提示血脑屏障破坏，同时MMP-9和NOS2表达上调。蛋白质印迹结果表明p-p38和p-ERK1/2表达增加。缺血再灌注后第7天，MMP-9和NOS2的表达与第2天大致相同，p-p38的表达高于第2天，p-ERK1/2的表达略低于第2天。SalB（1和10 mg·kg-1）显著减轻脑缺血再灌注诱导的免疫球蛋白外渗（P<0.05）。在第2天和第7天，SalB减弱了MMP-9和NOS2的表达（P<0.05）。SalB（10 mg·kg-1）在缺血再灌注后第2天和第7天明显降低了p-p38和p-ERK1/2的表达（P<0.05）。SalB（1 mg·kg-1）在缺血再灌注后第7天抑制了p-p38的表达（P<0.05）。结果表明，SalB通过抑制丝裂原活化蛋白激酶（MAPK）途径保护大鼠脑缺血再灌注后的血脑屏障。
