丁苯酞对脊髓损伤大鼠神经运动功能的保护作用及机制研究  

Protective effect and mechanism of butylphthalide on spinal cord injury rats

作　　者：江玲军[1] 陈之瑜 叶嘉靖 郑彬彬 陈忠义[1] JIANG Ling-jun;CHEN Zhi-yu;YE Jia-jing;ZHENG Bin-bin;CHEN Zhong-yi(Department of Orthopedics, Taizhou Hospital of Zhejiang Province, Taizhou 317000 y Zhejiang Province, China)

机构地区：[1]浙江省台州医院骨科

出　　处：《中国临床药理学杂志》2019年第16期1765-1769,共5页The Chinese Journal of Clinical Pharmacology

基　　金：浙江省自然基金资助项目(LGF18H060011)

摘　　要：目的研究丁苯酞对脊髓损伤大鼠神经运动功能的保护作用及作用机制。方法将120只大鼠随机分为假手术组、模型组和低、高剂量实验组。高、低剂量实验组分别给予80,20mg·kg-1丁苯酞,每日灌胃给药1次,连续给药7d;假手术组及模型组大鼠给予等体积的麻油。观察大鼠下肢功能、脊髓含水量、血-脊髓屏障通透性和脊髓组织形态。用末端脱氧核苷酸转移酶标记法(TUNEL)染色检测细胞凋亡率,用逆转录聚合酶链式反应(RT-PCR)法检测转录因子(CHOP)、葡萄糖调节蛋白(GRP78)及胱天蛋白酶12(caspase-12)mRNA表达情况,用蛋白免疫印迹(Westernblot)法检测CHOP、GRP78及caspase-12蛋白表达情况。结果给药7d后,假手术组、模型组和高、低剂量实验组大鼠下肢功能评分分别为(20.60±0.52),(2.70±0.67),(8.20±0.92),(3.80±0.79)分;脊髓含水量分别为(67.32±3.03)%,(78.21±3.66)%,(72.74±3.19)%,(77.95±3.54)%;EB含量为(2.36±0.92),(6.18±1.74),(3.89±1.12),(5.85±1.42)μg·g-1;脊髓组织细胞凋亡率分别为(3.66±0.82)%,(23.57±2.18)%,(11.62±1.73)%,(20.27±1.86)%;脊髓组织中CHOPmRNA含量分别为1.36±0.32,2.68±0.51,1.79±0.38,2.31±0.46;脊髓组织中GRP78mRNA含量分别为1.04±0.13,1.98±0.35,1.49±0.27,1.75±0.31;脊髓组织中caspase-12mRNA含量分别为0.43±0.12,0.99±0.25,0.62±0.16,0.84±0.22;脊髓组织中CHOP蛋白含量分别为0.87±0.11,1.45±0.18,0.94±0.11,1.30±0.15;脊髓组织中GRP78蛋白含量分别为0.29±0.09,0.65±0.15,0.34±0.11,0.56±0.13;脊髓组织中caspase-12蛋白含量分别为0.43±0.12,0.99±0.25,0.62±0.16,0.89±0.22,假手术组、高剂量实验组与模型组比较,差异均有统计学意义(均P<0.05)。结论80mg·kg-1丁苯酞对脊髓损伤大鼠神经运动功能具有保护作用,并可抑制脊髓损伤所致的内质网应激的发生。Objective To explore the protective effect and mechanism of butylphthalide on neuromotor function in rats with spinal cord injury. Methods A total of 120 rats were randomly divided into sham operation group, model group and high, low dose experimental groups. High, low dose experimental groups were given 80, 20 mg·kg-1 butylphthalide, oral administration once a day for 7 d;rats in sham operation group and model group were given an equal volume of sesame oil. The protective effect of butylphthalide on spinal cord injury rats were evaluated by exa-mining the lower limb function, spinal cord water content, blood-spinal barrier permeability and spinal cord histomorphology. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling( TUNEL) staining was used to detect apoptosis rate,reverse transcription-polymerase chain reaction( RT-PCR) was used to detect expressions of C/EBP-homologous protein( CHOP),immunoglobulin-binding protein( GRP) 78 and cysteinyl aspartate specific proteinase( caspase)-12 mRNA,and Western blot was used to detect expressions of CHOP,GRP78 and caspase-12 proteins. Results After 7 d of administration,the scores of lower limbs function in sham operation group,model group and high,low dose experimental groups were 20. 60 ± 0. 52,2. 70 ± 0. 67,8. 20 ± 0. 92,3. 80 ± 0. 79;the spinal cord water content were( 67. 32 ± 3. 03)%,( 78. 21 ± 3. 66)%,( 72. 74 ±3. 19)%,( 77. 95 ± 3. 54)%;the EB contents were( 2. 36 ± 0. 92),( 6. 18 ± 1. 74),( 3. 89 ± 1. 12),( 5. 85 ± 1. 42)μg·g-1;the apoptotic rates were( 3. 66 ± 0. 82)%,( 23. 57 ± 2. 18)%,( 11. 62 ± 1. 73)%,( 20. 27 ±1. 86)%;the content of CHOP mRNA were 1. 36 ± 0. 32,2. 68 ± 0. 51,1. 79 ± 0. 38,2. 31 ± 0. 46;the content of GRP78 mRNA were 1. 04 ± 0. 13,1. 98 ± 0. 35,1. 49 ± 0. 27,1. 75 ± 0. 31;the content of caspase-12 mRNA were 0. 43 ± 0. 12,0. 99 ± 0. 25,0. 62 ± 0. 16,0. 84 ± 0. 22;the expression of CHOP were 0. 87 ± 0. 11,1. 45 ± 0. 18,0. 94 ± 0. 11,1. 30 ± 0. 15;the expression of GRP78 were 0. 29 ± 0. 09,0

关 键 词：丁苯酞 脊髓损伤 细胞凋亡 内质网应激 

分 类 号：R971[医药卫生—药品]