摘要
Abstract
Objective To observe the neuroprotection of Puerarin on cerebral ischemia reperfusion injury and investigate its effect on the expression of estrogen receptor α (ER-α) , hypoxia inducible factor-1 (HIF-1α) and related inflammatory cytokines. Methods Mice were randomly divided into a sham group, a solvent-control group and three Puerarin-treated groups with different doses (100, 250, 500 mg·kg-1). Middle cerebral artery occlusion (MCAO) model was made and then the infarct volume, water content and neurological scores were evaluated after 2 h ischemia and 24 h reperfusion. Western blot was used to determine the expression of ER-α and HIF-1α after 2 h, 6 h, 12 h, 24 h reperfusion respectively. Both Western blot and ELISA were used to determine the effect of Puerarin on the expression of ER-α, HIF-1α and related inflammatory cytokines such as tumor necrosis factor-α (TNF- α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in 2 h ischemia and 12 h reperfusion mice. Results Compared with solvent-control group, Puerarin reduced the infarct volume [low dose group(29.6±3.6)%,medium dose group(15.2±3.9)%,high dose group(8.2±2.1)% vs control group (39.3±5.0)%] and water content [low dose group (84.9±8.8)%, medium dose group (83.7±8.2)%, high dose group(80.9±8.7)% vs control group(85.3±10.2)%],which had significant difference.It also activated ER-α and suppressed HIF-1α. In addition, medium and high dose of Puerarin further inhibited TNF-α [(420.7± 27.2) μg·g-1, (379.6±23.9) μg·g-1], IL-1β [(211.8±19.2) μg·g-1, (182.4±13.5) μg·g-1] and IL-6 [(111.2±9.1) μg·g-1, (104.1±12.4) μg·g-1] respectively compared to solvent control group [TNF-α (505.8±36.7) μg·g-1; IL-1β (291.6±21.8) μg·g-1; IL-6 (138.4±11.7) μg·g-1] in 2 h ischemia and 12 h reperfusion mice. Conclusion Puerarin within certain range of doses could reduce the water content and infarct volume of cerebral ischemia reperfusion injury. Its mechanism might be linked to activation of ER-α, inhibition the expression of HIF-1α, and the inhibition of release of related inflammatory cytokines such as TNF-α, IL-1β and IL-6.关键词
葛根素/脑缺血再灌注/雌激素受体/缺氧诱导因子-1α/炎性细胞因子Key words
Puerarin/Cerebral ischemia reperfusion/Estrogen receptor/Hypoxia inducible factor-1α/Inflammatory cytokines
