姜黄素预处理保护急性脊髓损伤小鼠神经功能与转化生长因子激酶1的相关性研究

Protective effect of curcumin preconditioning on neurologic function in mice with acute spinal cord injury and its correlation with transforming growth factor-activated kinase 1 pathway

目的研究姜黄素预处理对小鼠急性脊髓损伤后神经功能的保护作用及其可能机制。方法小鼠按体重随机分为假手术组、模型组、3个剂量(姜黄素,50,100,200 mg·kg^(-1))实验组,造模前30 min,分别腹腔注射生理盐水或相应药物,用改良的Allen’s法建立急性脊髓损伤模型后,作行为学评价,免疫印迹法测脊髓转化生长因子激酶1(TAK1)、p-TAK1、丝裂原蛋白激酶激酶6(MKK6)、p-MKK6、p38和p-p38蛋白表达。结果实验组,脊髓损伤48 h后旷场实验(BMS)评分由低到高依次为(0.80±0.79),(1.20±0.63),(1.60±0.52),较模型组的(0.70±0.48)均有不同程度改善;且实验组显著抑制了TAK1、MKK6和p-38的磷酸化,且呈现浓度依赖性。结论预防性应用姜黄素,可能通过抑制TAK1通路起到神经功能保护作用。

Objective To explore the protective effect of curcumin preconditioning on neurologic function in acute spinal cord model（SCI）mice and its possible mechanism. Methods Divide healthy and clean class mice into sham-operated group,model group,low-dose,middle-dose and high-dose test groups（curcumin,50,100,200 mg·kg^-1）. Each mouse respectively was given intraperitoneal injection of drugs at 30 min before the surgery. Then,establish experimental animal models following improved Allen＇ s model. The behavior evaluation was performed on mice. The transforming growth factor-activated kinase 1（TAK1）,p-TAK1,MKK6,p-MKK6,p38 and p-p38 antibody expression were examined with Western blot. Results Compared with the model group（0. 70 ± 0. 48）,after 48 h SCI,the Basso mouse scale（BMS）scores in test group from low to high dose（0. 80 ± 0. 79）,（1. 20 ± 0. 63）,（1. 60 ± 0. 52） were improved with different degrees.The curcumin markedly inhibited various inflammatory mediators induced by SCI-induced. Curcumin also significantly down-regulated the phosphorylation levels of TAK1,mitogen-activated protein kinase kinase 6（MKK6） and p38 MAPKs,which played key roles in microglia-mediated inflammatory response. Curcumin could significantly improve thefunctional recovery compared to the mice without curcumin treatment（BMS assay）. Conclusion The preliminary study shows that the way of curcumin preconditioning to improve neurologic function may via TAK1 /（MKK6） / p38 pathway.