Lin Xuemei, Yu Shanshan, Chen Yanlin, Wu Jingxian, Zhao Jing, Zhao Yong
Department of Pathology, Chongqing Medical University, Chongqing, China.
Neurol Res. 2012 Jan;34(1):32-7. doi: 10.1179/1743132811Y.0000000054.
Diallyl sulfide (DAS) is the main organosulfur component of garlic and it is known for multiple pharmacological actions. Recent studies have demonstrated that DAS has neuroprotective effects against ischemia/reperfusion injury. While some of the possible mechanisms behind this protection have been explored, its ability to inhibit apoptosis has yet to be fully explained. In the present study, the effects of DAS on focal cerebral ischemia in rats were tested and its anti-apoptotic action was explored.
To examine the protective effects of DAS, focal cerebral ischemia/reperfusion was induced in rats by transient middle cerebral artery occlusion for 2 hours followed by reperfusion for 24 hours. The animals received DAS in quantities of 100, 150, and 200 mg/kg (intraperitoneal; every day), for 7 days before transient middle cerebral artery occlusion. The neurological score and infarct volume were measured at 24 hours after the end of reperfusion. Apoptotic cells were counted by terminal dUTP nick end labeling staining and apoptotic mechanisms were studied by fluorescence immunohistochemistry staining and western blot analysis.
For animals with induced ischemia/reperfusion, those pretreated with 200 mg/kg DAS showed an infarct volume (22.36 ± 0.67%) significantly lower than that of the non-treated ischemia/reperfusion group (38.23 ± 0.72%), and the percentage of terminal dUTP nick-end labeling-positive cells (23.46 ± 1.02%) of the DAS-pretreated group was also significantly decreased compared to non-treated (36.41 ± 1.58%). Fluorescence immunohistochemistry staining and western blot analysis indicated that DAS reduced caspase-3 expression and increased Bcl-2 expression.
These results suggest that the mechanism by which DAS protects the brain from ischemia/reperfusion injury is related to its anti-apoptotic effects in part.
二烯丙基硫醚（DAS）是大蒜的主要有机硫成分，具有多种药理作用。近期研究表明，DAS对缺血/再灌注损伤具有神经保护作用。虽然已经探索了这种保护作用背后的一些可能机制，但其抑制细胞凋亡的能力尚未得到充分解释。在本研究中，测试了DAS对大鼠局灶性脑缺血的影响，并探讨了其抗凋亡作用。
为了检测DAS的保护作用，通过短暂阻断大脑中动脉2小时后再灌注24小时，诱导大鼠局灶性脑缺血/再灌注。在短暂阻断大脑中动脉前7天，动物每天腹腔注射100、150和200mg/kg的DAS。在再灌注结束后24小时测量神经学评分和梗死体积。通过末端脱氧核苷酸转移酶介导的缺口末端标记染色对凋亡细胞进行计数，并通过荧光免疫组织化学染色和蛋白质印迹分析研究凋亡机制。
对于诱导缺血/再灌注的动物，用200mg/kg DAS预处理的动物梗死体积（22.36±0.67%）显著低于未处理的缺血/再灌注组（38.23±0.72%），并且与未处理组（36.41±1.58%）相比，DAS预处理组的末端脱氧核苷酸转移酶介导的缺口末端标记阳性细胞百分比（23.46±1.02%）也显著降低。荧光免疫组织化学染色和蛋白质印迹分析表明，DAS降低了半胱天冬酶-3的表达并增加了Bcl-2的表达。
这些结果表明，DAS保护大脑免受缺血/再灌注损伤的机制部分与其抗凋亡作用有关。
