桂皮醛对脑缺血小鼠的脑保护作用及对Toll样受体6/核因子-κB信号通路的影响

目的探讨桂皮醛对局灶性脑缺血小鼠的脑保护作用及机制。方法雄性CD-1小鼠通过腹腔注射的方法给予桂皮醛干预,应用改良线栓法建立小鼠右侧永久性大脑中动脉闭塞模型,将成年健康雄性CD-1小鼠随机分为大脑中动脉闭塞(MCAO)组及桂皮醛(CA)低、中、高剂量干预组,即CA25组、CA50组和CA75组(在MCAO小鼠模型基础上腹腔给予25 mg/kg、50 mg/kg及75 mg/kg桂皮醛)。术后24 h通过测定小鼠神经功能缺损评分、脑梗死体积及脑组织含水量来评价桂皮醛的脑保护作用。通过Western blot法和实时荧光定量PCR法测定Toll样受体6(TLR6)、肿瘤坏死因子受体相关分子6(TRAF6)和核因子-κB(NF-κB)在脑组织中的表达。结果与MCAO组相比,CA50组神经功能评分显著改善(中位数2.0 vs.3.5),病变侧脑组织含水量降低(83.72±0.73)%vs.(85.09±0.95)%],脑梗死体积缩小(0.45±0.06 vs.0.54±0.02),均P0.05。同样与MCAO组相比,CA50组TLR6、TRAF6及NF-κB基因表达明显下调(TLR6:3.26±0.03 vs.6.32±0.07;TRAF6:1.88±0.21 vs.3.33±0.48;NF-κB:1.47±0.33 vs 4.21±0.57,均P0.05)。TLR6、TRAF6及胞核NF-κB蛋白表达明显下降(TLR6:0.12±0.01 vs.0.19±0.03;TRAF6:0.45±0.09 vs.0.67±0.07;胞核NF-κB:0.32±0.06 vs.0.46±0.06,均P0.05)。结论桂皮醛可能通过抑制TLR6/TRAF6/NF-κB通路对局灶性脑缺血小鼠发挥脑保护作用。

Cerebral protective effect of cinnamaldehyde and its influence on the Toll-like receptor 6/nuclear factor-kappa B signaling pathway in mice with cerebral ischemia

Objective To investigate the cerebral protective effect of cinnamaldehyde (CA) in mice with focal cerebral ischemia and related mechanism.Methods Male CD-1 mice were treated with intraperitoneal injection of CA, and the modified suture method was used to establish a mouse model of permanent right middle cerebral artery occlusion (MCAO). Healthy adult male CD-1 mice were randomly divided into MCAO group and low-, middle-, and high-dose CA groups (CA25, CA50, and CA 75 groups treated with intraperitoneal injection of CA at concentrations of 25, 50, and 75 mg, respectively, in addition to the treatment in the MCAO group). At 24 hours after surgery, neurologic impairment score, cerebral infarct volume, and brain water content were measured to evaluate the cerebral protective effect of CA. Western blot and quantitative real-time PCR were used to measure the expression of Toll-like receptor 6 (TLR6), tumor necrosis factor receptor-associated factor 6 (TRAF6), and nuclear factor-kappa B (NF-κB) in brain tissue.Results Compared with the MCAO group, the CA50 group had a significant improvement in median neurological score (2.0 vs 3.5, P<0.05) and significant reductions in brain water content (83.72%±0.73% vs 85.09%±0.95%, P<0.05) and cerebral infarct volume (0.45±0.06 vs 0.54±0.02, P<0.05). Compared with the MCAO group, the CA50 group had significant reductions in the mRNA expression of TLR6, TRAF6, and NF-κB (TLR6:3.26±0.03 vs 6.32±0.07, P<0.05; TRAF6:1.88±0.21 vs 3.33±0.48, P<0.05; NF-κB:1.47±0.33 vs 4.21±0.57, P<0.05), as well as significant reductions in the protein expression of TLR6, TRAF6, and nuclear NF-κB (TLR6:0.12±0.01 vs 0.19±0.03, P<0.05; TRAF6:0.45±0.09 vs 0.67±0.07, P<0.05; NF-κB:0.32±0.06 vs 0.46±0.06, P<0.05).Conclusions CA exerts a cerebral protective effect in mice with focal cerebral ischemia, possibly by inhibiting the TLR6/TRAF6/NF-κB signaling pathway.