依达拉奉联合黄体酮对衰老脑出血小鼠模型神经功能恢复效果及其机制研究  

Effect of edaravone combined with progesterone on nerve function recovery in aged ICH mice and its mechanism

作　　者：郑建新[1] 王爽[1] 凌会敏 王洵[1] Zheng Jianxin;Wang Shuang;Ling Huimin;Wang Xun(Department of Neurology,Affiliated No.2 Hospital of Luohe Medical School,Xuchang 462300,Henan Province,China)

机构地区：[1]漯河医学高等专科学校第二附属医院神经内科,许昌462300

出　　处：《中华老年心脑血管病杂志》2020年第6期639-643,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：漯河医学高等专科学校研究项目(17B320010)。

摘　　要：目的研究依达拉奉联合黄体酮(progesterone)对衰老脑出血小鼠模型神经功能恢复效果及其机制。方法140只雄性小鼠(20~22月龄)根据随机数字表法分成4组,假手术组、模型组、依达拉奉组、依达拉奉和黄体酮联合用药组(联合组),每组35只。采用脑部纹状体内注射胶原酶的方法建立小鼠的脑出血模型,依达拉奉组于术后2 h腹腔注射依达拉奉3 mg/kg,2次/d;联合组在依达拉奉组基础上腹腔注射黄体酮8 mg/kg,1次/d;模型组和假手术组(未建模)腹腔注射等体积的生理盐水,1次/d;4组均连续给药14 d。给药14 d后采用改良神经功能缺损评分(mNSS)评估各组小鼠神经损伤严重程度,并测定小鼠脑组织含水量及脑损伤体积,用酶联免疫吸附法测定血清中氧化应激指标水平,采用Western blot法检测脑组织中磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)信号通路相关蛋白水平。结果模型组mNSS、脑组织含水量最高,假手术组mNSS、脑组织含水量最低,联合组mNSS、脑组织含水量显著低于依达拉奉组和模型组(P<0.01)。联合组脑组织肿胀率、脑损伤体积显著低于依达拉奉组和模型组[(6.56±2.26)%、(2.04±0.62)mm^3vs(10.34±3.28)%、(3.19±0.70)mm^3和(14.56±4.26)%、(3.84±0.72)mm^3,P<0.05]。假手术组超氧化物歧化酶(SOD)水平最高,模型组丙二醛、活性氧、白细胞介素6(IL-6)、TNF-α水平最高,依达拉奉组丙二醛、活性氧、IL-6、TNF-α水平显著高于联合组,SOD显著低于联合组(P<0.05)。与依达拉奉组比较,假手术组、模型组PI3K、Akt、磷酸化-PI3K、磷酸化-Akt水平显著降低,NF-κB、半胱氨酸天冬氨酸蛋白酶9(Caspase-9)水平显著增高,联合组PI3K、Akt、磷酸化-PI3K、磷酸化-Akt水平显著增高,NF-κB、Caspase-9水平显著降低(P<0.05);与联合组比较,假手术组、依达拉奉组、模型组PI3K、Akt、p-PI3K、p-Akt水平降低,NF-κB、Caspase-9水平增高,差异有统计学意义(P<0.05)。结�Objective To study the effect of edaravone combined with progesterone on nerve function recovery in aged ischemic cerebral hemorrhage(ICH)mice and its mechanism.Methods One hundred and forty male mice aged 20-22 months were divided into sham operation group,model group,edaravone treatment group and edaravone+progesterone treatment group(35 in each group).A cerebral hemorrhage model of mice was established by injecting collagenase into the striatum of brain.Fourteen days after the mice in edaravone treatment group,edaravone+progesterone treatment group,model group received the same volume of saline(once a day),and those in sham operation group were intraperitoneally injected with edaravone(3 mg/kg,twice a day),progesterone solution(8 mg/kg,once a day)plus edaravone(3 mg/kg,twice a day)and only an equal volume of normal saline respectively,the water content in brain tissue,swelling rate and volume of brain tissue were assayed.The serum levels of oxidative stress-related indexes and PI3 K/Akt signaling pathway-related proteins in brain tissue were measured by ELIA and Western blot respectively.Results The mNNSS score and water content in brain tissue were the highest in model group and the lowest in sham operation group.The mNNSS score and water content in brain tissue were significantly lower in edaravone+progesterone treatment group than in edaravone treatment group and model group(P<0.05).The swelling rate of brain tissue was significantly lower and the volume of brain injury was significantly smaller in edaravone+progesterone treatment group than in edaravone treatment group and model group(6.56%±2.26%vs 10.34%±3.28%and 14.56%±4.26%,2.04±0.62 mm^3 vs 3.19±0.70 mm^3 and 3.84±0.72 mm^3,P<0.05).The serum levels of SOD were the highest in sham operation group and those of MDA,ROS,IL-6,TNF-αwere the highest in model group.The serum levels of MDA,ROS,IL-6 and TNF-αwere significantly higher while those of SOD were significantly lower in sham operation group than in model group(P<0.05).The serum levels of PI3 K,

关 键 词：孕酮 脑出血 超氧化物歧化酶 白细胞介素6 半胱氨酸天冬氨酸蛋白酶9 

分 类 号：R-332[医药卫生] R743.34