铁皮石斛多糖对缺血性脑卒中大鼠脑组织JAK/STAT3信号通路的影响

Effect of dendrobium officinale polysaccharide on JAK/STAT3 signaling pathway in brain tissue of ischemic stroke rats

[目的]探讨铁皮石斛多糖(DOP)对缺血性脑卒中大鼠脑组织Janus激酶(JAK)/信号转导子和转录激活子3(STAT3)信号通路的影响。[方法]以线栓法建立大脑中动脉闭塞大鼠模型。SD大鼠随机分为模型组、DOP低剂量(25μg/g)组、DOP中剂量(50μg/g)组、DOP高剂量(100μg/g)组、依达拉奉组,每组12只;另取12只SD大鼠设为假手术组。经药物干预后,以Longa分级法对各组大鼠进行神经功能缺损评分;通过三苯基氯化四氮唑染色检测大鼠脑梗死情况;苏木精-伊红染色观察大鼠海马神经组织病理形态变化;酶联免疫吸附法检测大鼠脑组织炎性细胞因子干扰素γ(IFN-γ)、环氧合酶2(COX-2)、白细胞介素6(IL-6)水平;Western blot检测大鼠脑组织JAK/STAT3信号通路相关蛋白表达水平。[结果]与假手术组相比,模型组大鼠海马神经元皱缩、变小,变性坏死,结构破损,排列紊乱,且数目明显减少,海马神经组织整体呈现明显病理损伤,神经功能缺损评分、脑梗死面积、脑组织IFN-γ、COX-2及IL-6水平、p-JAK/JAK、p-STAT3/STAT3明显升高(P<0.05)。与模型组相比,药物处理组大鼠海马神经组织病理损伤减轻,神经功能缺损评分、脑梗死面积、脑组织IFN-γ、COX-2及IL-6水平、p-JAK/JAK、p-STAT3/STAT3均降低,且DOP各组之间呈剂量依赖性(P<0.05)。DOP高剂量组与依达拉奉组比较,大鼠各指标均无明显变化(P>0.05)。[结论]DOP可抑制缺血性脑卒中大鼠JAK/STAT3信号通路激活,减少炎性细胞因子合成分泌,减轻脑部炎症,修复神经功能。

Aim To investigate the effect of dendrobium officinale polysaccharide(DOP)on Janus kinase(JAK)/signal transducer and activator of transcription 3(STAT3)signaling pathway in brain tissue of ischemic stroke rats.Methods The rat model of middle cerebral artery occlusion was established by thread embolism.SD rats were randomly divided into model group,DOP low dose(25μg/g)group,DOP medium dose(50μg/g)group,DOP high dose(100μg/g)group and edaravone group,with 12 rats in each group;Another 12 SD rats were set as sham operation group.After drug intervention,the neurological deficit of rats in each group was scored by Longa grading method.The cerebral infarction in rats was detected by triphenyltetrazolium chloride staining.Hematoxylin-eosin staining was used to observe the pathological changes of hippocampal nerve tissue in rats.Enzyme-linked immunosorbent assay was used to detect the levels of inflammatory cytokines interferon-γ(IFN-γ),cyclooxygenase-2(COX-2)and interleukin-6(IL-6)in rat brain.Western blot was used to detect the expression level of JAK/STAT3 signaling pathway related proteins in rat brain.Results Compared with the sham operation group,the hippocampal neurons in the model group were shriveled,smaller,degenerated and necrotic,damaged in structure and disordered in arrangement,and the number of them decreased obviously.The whole hippocampal nerve tissue showed obvious pathological damage,and the neurological deficit score,cerebral infarction area,levels of IFN-γ,COX-2 and IL-6 in brain tissue,p-JAK/JAK,p-STAT3/STAT3 increased obviously(P<0.05).Compared with the model group,the pathological damage of hippocampal nerve tissue in the drug treatment group was reduced,the neurological deficit score,cerebral infarction area,the levels of IFN-γ,COX-2 and IL-6 in brain tissue,p-JAK/JAK,p-STAT3/STAT3 were all decreased,and there was a dose-dependent relationship among DOP groups(P<0.05).Compared with edaravone group,there was no significant change in all indexes of rats in DOP high dose group(P>0.05).Conclusion DOP can inhibit the activation of JAK/STAT3 signaling pathway in ischemic stroke rats,reduce the synthesis and secretion of inflammatory cytokines,relieve brain inflammation and repair nerve function.