胡黄连苷Ⅱ调节JAK2/STAT3信号通路对血管性痴呆大鼠的神经保护作用  

Neuroprotective Effect of PicrosideⅡon Vascular Dementia Rats by Regulating the JAK2/STAT3 Signaling Pathway

作　　者：宋征宇[1] 王嘉南 张颖 高海静 史可心 王玲玲 SONG Zhengyu;WANG Jianan;ZHANG Ying;GAO Haijing;SHI Kexin;WANG Lingling(Department of Neurology,the First Affiliated Hospital of Hebei North University,Zhangjiakou 075000 Hebei,China)

机构地区：[1]河北北方学院附属第一医院神经内科,河北张家口075000

出　　处：《中药新药与临床药理》2024年第12期1851-1857,共7页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：河北省卫健委、财政厅2023年政府资助临床医学优秀人才培养项目(ZF2023238)。

摘　　要：目的探讨胡黄连苷Ⅱ调节JAK2/STAT3信号通路对血管性痴呆大鼠的神经保护作用。方法将SD大鼠随机分为假手术组、模型组、胡黄连苷Ⅱ低剂量组、胡黄连苷Ⅱ高剂量组、胡黄连苷Ⅱ高剂量+Colivelin(JAK2/STAT3信号通路激活剂)组。Zea-Longa法评估大鼠神经功能;神经髓鞘固蓝(LFB)染色法观察各组大鼠胼胝体髓鞘的形态;ELISA法检测大鼠血清中肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-6和IL-10水平;HE染色观察大鼠海马组织形态变化;商品化试剂盒检测海马组织中脑源性神经营养因子(BDNF)、丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)水平;WesternBlot法检测大鼠海马组织Cleaved-Caspase-3、MBP、Olig1、p-JAK2/JAK2、p-STAT3/STAT3蛋白表达。结果与假手术组相比,模型组大鼠胼胝体内髓鞘结构和海马组织CA1区有明显损伤,神经功能评分、血清TNF-α和IL-6水平、海马组织MDA水平、Cleaved-Caspase-3、p-JAK2/JAK2和p-STAT3/STAT3蛋白表达水平明显升高,血清IL-10水平、海马组织中BDNF、SOD和CAT水平、MBP和Olig1蛋白表达水平明显降低(均P<0.05)。与模型组比,胡黄连苷Ⅱ低剂量组和胡黄连苷Ⅱ高剂量组大鼠胼胝体内髓鞘结构和海马组织CA1区有损伤明显减轻,神经功能评分、血清TNF-α和IL-6水平、海马组织MDA水平、Cleaved-Caspase-3、p-JAK2/JAK2和p-STAT3/STAT3蛋白表达水平明显降低,血清IL-10水平、海马组织中BDNF、SOD和CAT水平、MBP和Olig1蛋白表达水平明显升高(均P<0.05),且呈剂量依赖性改善(P<0.05)。与胡黄连苷Ⅱ高剂量组比,Colivelin可减轻胡黄连苷Ⅱ对血管性痴呆大鼠神经的保护作用(P<0.05)。结论胡黄连苷Ⅱ可能通过抑制JAK2/STAT3信号通路来降低血管性痴呆大鼠氧化应激、炎症和神经组织损伤,修复损伤髓鞘,改善神经功能。Objective To investigate the neuroprotective effect of picrosideⅡon vascular dementia(VD)rats by regulating the JAK2/STAT3 signaling pathway.Methods SD rats were randomly separated into the sham operated group,the model group,picrosideⅡlow-dose group,picrosideⅡhigh-dose group,and picrosideⅡhigh-dose+colivelin(the JAK2/STAT3 signaling pathway agonist)group.Zea-Longa method was applied to evaluate the neural function of rats.Luxol fast blue(LFB)staining method was applied to observe the morphology of the myelin sheaths in corpus callosum of each group.ELISA method was applied to detect the levels of TNF-α,IL-6,and IL-10 in serum.The morphological changes of hippocampal tissue were observed by HE staining.The commercialized reagent kits were applied to detect the levels of BDNF,MDA,SOD,and CAT in hippocampal tissue.Western Blot was applied to detect the protein expression of Cleaved-Caspase-3,MBP,Olig1,p-JAK2/JAK2,and p-STAT3/STAT3 in hippocampal tissue.Results Compared with the sham operated group,the rats in the model group showed significant damage to the myelin sheath structure in the corpus callosum and the CA1 region in the hippocampal tissue.The neurological function score,serum TNF-αand IL-6 levels,as well as the protein expression of Cleaved-Caspase-3,p-JAK2/JAK2,and p-STAT3/STAT3 and MDA level in hippocampal tissues were significantly increased,the serum IL-10 level,BDNF,SOD,and CAT levels in hippocampal tissues,and the proteins expression of MBP and Olig1 were significantly reduced(P<0.05).Compared with the model group,the damage to the myelin sheath structure in the corpus callosum and the CA1 area of the hippocampal tissue in the picrosideⅡlow-and high-dose groups was significantly reduced.The neurological function score,serum TNF-αand IL-6 levels,the protein expression of Cleaved-Caspase-3,p-JAK2/JAK2,and p-STAT3/STAT3 and MDA level in hippocampal tissues were significantly reduced,while the serum IL-10 level,BDNF,SOD,and CAT levels in hippocampal tissues,as well as the protein expression

关 键 词：胡黄连苷Ⅱ JAK2/STAT3信号通路 血管性痴呆 神经保护 BDNF 大鼠 

分 类 号：R285.5[医药卫生—中药学]