ChongQing Medical University, China.
ChongQing General Hospital, China.
Int Immunopharmacol. 2017 Apr;45:74-78. doi: 10.1016/j.intimp.2017.01.034. Epub 2017 Feb 10.
Ischemia/reperfusion (I/R) injury has been correlated with systemic inflammatory response. In addition, NLRP3 has been suggested as a cause in many inflammatory processes. Sulforaphane (SFN) is a naturally occurring isothiocyanate found in cruciferous vegetables, such as broccoli and cabbage. While recent studies have demonstrated that Sulforaphane has protective effects against cerebral ischemia/reperfusion injury, little is known about how those protective effects work. In this study, we focus our investigation on the role and process of Sulforaphane in the inhibition of NLRP3 inflammasome activation, as well as its effect on brain ischemia/reperfusion injury. Adult male Sprague-Dawley rats were injected with Sulforaphane (5 or 10mg/kg) intraperitoneally at the beginning of reperfusion, after a 60min period of occlusion. A neurological score and infarct volume were assessed at 24h after the administration of Sulforaphane. Myeloperoxidase (MPO) activity was measured at 24h to assess neutrophil infiltration in brain tissue. ELISA, RT-PCR and Western blot analyses were used to measure any inflammatory reaction. Sulforaphane treatment significantly reduced infarct volume and improved neurological scores when compared to a vehicle-treated group. Neutrophil infiltration was significantly higher in the vehicle-treated group than in the Sulforaphane treatment group. Sulforaphane treatment inhibits NLRP3 inflammasome activation and the downregulation of cleaved caspase-1, while reducing IL-1β and IL-18 expression. The inhibition of inflammatory response with Sulforaphane treatment improves outcomes after focal cerebral ischemia. This neuroprotective effect is likely exerted by Sulforaphane inhibited NLRP3 inflammasome activation caused by the downregulation of NLRP3, the induction of cleaved caspase-1, and thus the reduction of IL-1β and IL-18.
缺血再灌注（I/R）损伤与全身炎症反应有关。此外，NLRP3 已被认为是许多炎症过程的原因。萝卜硫素（SFN）是一种存在于十字花科蔬菜中的天然异硫氰酸盐，如西兰花和卷心菜。虽然最近的研究表明萝卜硫素有保护作用，可以对抗脑缺血再灌注损伤，但对其保护作用的机制知之甚少。在这项研究中，我们专注于萝卜硫素抑制 NLRP3 炎性小体激活的作用和过程，以及其对脑缺血再灌注损伤的影响。成年雄性 Sprague-Dawley 大鼠在再灌注开始时通过腹腔注射萝卜硫素（5 或 10mg/kg），闭塞 60 分钟后。在给予萝卜硫素 24 小时后评估神经评分和梗死体积。在 24 小时测量髓过氧化物酶（MPO）活性以评估脑组织中的中性粒细胞浸润。ELISA、RT-PCR 和 Western blot 分析用于测量任何炎症反应。与载体处理组相比，萝卜硫素处理显著降低了梗死体积并改善了神经评分。与萝卜硫素处理组相比，载体处理组的中性粒细胞浸润明显更高。萝卜硫素处理抑制 NLRP3 炎性小体的激活和裂解 caspase-1 的下调，同时降低 IL-1β 和 IL-18 的表达。用萝卜硫素治疗抑制炎症反应可改善局灶性脑缺血后的结局。这种神经保护作用可能是通过萝卜硫素抑制 NLRP3 炎性小体的激活来实现的，其机制是下调 NLRP3，诱导裂解 caspase-1，从而减少 IL-1β 和 IL-18 的表达。
