忍冬苷对脑出血大鼠神经功能保护作用的研究

Study on the neuroprotective effect of lonicerin japonica glycosides on cerebral hemorrhage in rats

目的研究忍冬苷(lonicerin,LN)对脑出血大鼠神经功能缺损和脑组织病理形态学变化及炎症相关蛋白表达的影响,探讨对脑出血大鼠的神经功能保护作用及其机制。方法采用随机数字表法将72只成年雄性SD大鼠分为假手术组(SHAM组,n=24)、脑出血组(ICH组,n=24)、ICH+忍冬苷组(LN组,n=24)。造模后,LN组予以忍冬苷10mg/(kg·d)腹腔注射,SHAM组和ICH组给予等剂量磷酸盐缓冲液腹腔注射。比较3组在1d、3d、5d、7d后,Longa评分Toll样受体4(Toll-like receptor 4,TLR4)、髓样分化因子88(myeloid differentiation factor 88,MyD88)、核转录因子κB(nuclear factor-kappaB,NF-κB)蛋白的表达水平,以及脑组织中肿瘤坏死因子α(tumor necrosis factor-alpha,TNF-α)含量。结果ICH组和LN组在1d、3d、5d、7d的Longa评分均高于SHAM组,差异有统计学意义(P<0.05)。ICH组和LN组在1d、3d、5d、7d均出现不同程度的病理损伤,LN组各时间点的病理损伤性改变均较相同时期ICH组减轻。SHAM组和LN组1d、3d、5d、7d脑组织的TLR4、MyD88、NF-κB蛋白水平和TNF-α含量均低于ICH组,差异有统计学意义(P<0.05)。结论忍冬苷可改善脑出血大鼠神经功能缺损症状,减轻脑出血后脑组织继发性炎症病理损害,具有神经保护作用,其机制可能与其下调TLR4/MyD88/NF-κB信号通路相关蛋白表达并抑制炎症因子TNF-α的过度表达有关。

Objective To study the effects of lonicerin(LN)on the neurological deficit,pathological changes of brain tissue and expression of inflammatory related proteins in rats with intracerebral hemorrhage(ICH),and to explore the neuroprotective effect of LN on ICH and its mechanism.Methods A total of 72 adult male SD rats were divided into sham operation group(SHAM group,n=24),cerebral hemorrhage group(ICH group,n=24)and ICH+honeysuckle group(LN group,n=24)according to random number table method.After modeling,the LN group was intraperitoneally injected with 10mg/(kg·d)of honeysuckle glycoside,and the SHAM group and ICH group were intraperitoneally injected with the same dose of phosphate buffer solution.The expression levels of Toll like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),nuclear transcription factor kappa B(NF-κB)and tumor necrosis factor-alpha(TNF-α)in brain tissue of the three groups were compared after 1 day,3 days,5 days and 7 days.Results The Longa scores of ICH group and LN group were higher than those of SHAM group on the 1st,3rd,5th and 7th days,with significant differences(P<0.05).The ICH group and LN group showed different degrees of pathological damage on the 1st,3rd,5th and 7th days,and the pathological changes at each time point in LN group were less than those in ICH group at the same period,and the levels of TLR4,MyD88,NF-κB protein and TNF-αin brain tissue of SHAM group and LN group on the 1st,3rd,5th and 7th days were lower than those of ICH group,and the differences were statistically significant(P<0.05).Conclusion Honeysuckle glycoside can improve the neurological deficit symptoms of rats with intracerebral hemorrhage,alleviate the secondary inflammatory pathological damage of brain tissue after intracerebral hemorrhage,and has neuroprotective effect.Its mechanism may be related to its down-regulation of TLR4/MyD88/NF-kB signal pathway related protein expression and inhibition of the overexpression of inflammatory factor TNF-α.