胡黄连苷Ⅱ调节cAMP/PKA信号轴对脊髓损伤大鼠神经功能恢复的影响  

Effect of picroside II on the recovery of neural function in spinal cord injury rats by regulating the cAMP/PKA signaling pathway

作　　者：范雁东[1] 王佳明[1] 马木提江·木尔提扎 罗坤 FAN Yandong;WANG Jiaming;MAMUTIJIANG·Muertizha(Department of Neurosurgery,the First Affiliated Hospital of Xinjiang Medical University,Xinjiang,Urumqi 830054,China)

机构地区：[1]新疆医科大学第一附属医院神经外科,乌鲁木齐市830054 [2]新疆医科大学第二附属医院神经外科

出　　处：《河北医药》2024年第9期1285-1290,共6页Hebei Medical Journal

基　　金：新疆维吾尔自治区自然科学基金青年基金(编号:2019D01C323)。

摘　　要：目的探讨胡黄连苷Ⅱ(PicrosideⅡ,PⅡ)对脊髓损伤(spinal cord injury,SCI)大鼠神经功能恢复的影响及对环磷酸腺苷(cAMP)-蛋白激酶A(PKA)信号通路的调节作用。方法建立SCI大鼠模型,大鼠分为正常组(CT组)、SCI模型组(SCI组)、PⅡ低剂量组(PⅡL组,5 mg·kg^(-1)·d^(-1))、PⅡ高剂量组(PⅡH组,20 mg·kg^(-1)·d^(-1))和PⅡ高剂量+PKA抑制剂组(PⅡH+H-89组,20 mg·kg^(-1)·d^(-1) PⅡ+5 mg·kg^(-1)·d^(-1)),每组18只。Basso-Beattie-Bresnahan(BBB)评分评价SCI大鼠运动功能,HE染色评价脊髓组织病理学特征,劳克坚牢蓝(LFB)染色观察脱髓鞘情况,免疫荧光检测胶质纤维酸性蛋白(GFAP)、离子钙结合适配器分子-1(IBA-1)表达,ELISA检测丙二醛(MDA)、超氧化物歧化酶(SOD)、环腺苷酸(cAMP)的含量,Western blot检测磷酸化(p)-PKA、PKA、p-环磷酸腺苷反应成分结合蛋白(CREB)、CREB蛋白表达。结果与CT组比较,SCI组大鼠脊髓组织缺损、空腔,大量炎性细胞浸润,脱髓鞘以及GFAP、IBA-1、MDA表达增加,BBB评分以及SOD、cAMP、p-PKA/PKA、p-CREB/CREB表达减少(P<0.05);与SCI组比较,PⅡL组、PⅡH组组织损伤改善,空腔及炎性细胞减少,脱髓鞘以及GFAP、IBA-1、MDA表达降低,BBB评分以及SOD、cAMP、p-PKA/PKA、p-CREB/CREB表达增加(P<0.05);与PⅡH组比较,PⅡH+H-89组组织损伤严重,脱髓鞘以及GFAP、IBA-1、MDA表达增加,BBB评分以及SOD、cAMP、p-PKA/PKA、p-CREB/CREB表达减少(P<0.05)。结论PⅡ可能通过激活cAMP/PKA信号轴促进SCI大鼠神经功能恢复。Objective To investigate the impact of picrosideⅡ(PⅡ)on the recovery of neural function in spinal cord injury(SCI)rats and its regulatory effect on the cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway.Methods The SCI rat model was established.Rats were randomly divided into control group(CT group),SCI group,low-dose PⅡgroup(PⅡL group,5 mg/kg/d),high-dose PⅡgroup(PⅡH group,20 mg/kg/d),and high-dose PⅡ+PKA inhibitor group(PⅡH+H-89 group,20 mg/kg/d PⅡ+5 mg/kg/d H-89).The Basso,Beattie and Bresnahan(BBB)scoring was applied to evaluate the motor function of SCI rats.Hematoxylin and eosin(H&E)and Luxol fast blue(LFB)staining were performed to evaluate the pathological characteristics of spinal cord tissue and demyelination,respectively.Immunofluorescence was applied to detect the expressions of glial fibrillary acidic protein(GFAP)and ion calcium binding adapter molecule-1(IBA-1).Enzyme-linked immunosorbent assay(ELISA)was applied to measure relative levels of malondialdehyde(MDA),superoxide dismutase(SOD)and cyclic adenosine monophosphate(cAMP).Western blot was applied to detect the protein expressions of phosphorylated PKA(p-PKA),PKA,phosphorylated cyclic adenosine phosphate responsive component binding protein(p-CREB)and CREB.Results Compared with those the CT group,rats in SCI group had spinal cord tissue defects,cavities,infiltration of massive inflammatory cells,demyelination,significantly higher levels of GFAP,IBA-1 and MDA,but lower BBB,relative levels of SOD and cAMP,p-PKA/PKA and p-CREB/CREB(P<0.05).Compared with rats of SCI group,rats in the PⅡL group and PⅡH group had alleviated histological injuries,reduced cavities,inflammatory cells and demyelination,significantly lower levels of GFAP,IBA-1 and MDA,but higher BBB,relative levels of SOD and cAMP,p-PKA/PKA and p-CREB/CREB(P<0.05).Compared with rats of PⅡH group,rats in PⅡH+H-89 group had severer histological injuries and demyelination,significantly higher levels of GFAP,IBA-1 and MDA,but lower BBB,relati

关 键 词：胡黄连苷Ⅱ 脊髓损伤 神经功能 环磷酸腺苷-蛋白激酶A 

分 类 号：R338.21[医药卫生—人体生理学]