蛋白酶体活性升高在1-BP致大鼠周围神经损伤中的作用  

Elevated proteasomal activities in rats peripheral nervous system exposed to 1-Bromopropane

作　　者：杨俊林[1] 王清华[1] 王增金[1] 赵秀兰[1] 

机构地区：[1]山东大学公共卫生学院毒理学系,山东济南250012

出　　处：《山东大学学报（医学版）》2016年第4期78-83,共6页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(81172708);山东省科技攻关计划(2011GSF11814)

摘　　要：目的探讨泛素蛋白酶体系统(UPS)在1-溴丙烷(1-BP)致大鼠周围神经病中的作用。方法 30只雄性Wistar大鼠随机分至对照组、400 mg/kg·bw组(低剂量组)和800 mg/kg·bw组(高剂量组),分别经口给予等体积的玉米油和1-BP(溶于玉米油),每日1次,每周5 d,连续16周。荧光检测法检测类胰蛋白酶、类糜蛋白酶和肽-谷氨酰肽水解酶(PGPH)在大鼠不同神经组织中的活性;蛋白电泳检测大鼠不同神经组织中的4-羟基壬烯醛(4-HNE)和丙二醛(MDA)蛋白质加合物水平,以及1-BP体外对4-HNE氧化修饰神经组织蛋白的促进作用。结果与对照组相比,低、高剂量组坐骨神经中类胰蛋白酶活性升高(P<0.01),高剂量组大脑中类糜蛋白酶活性升高(P<0.01),大脑和坐骨神经中PGPH活性升高(P<0.05);与对照组相比,低剂量组坐骨神经组织中4-HNE和MDA蛋白质加合物表达水平升高(P<0.01),高剂量组大脑和坐骨神经中4-HNE和MDA蛋白质加合物表达水平升高(P<0.01);1-BP促进了4-HNE对大脑、脊髓和坐骨神经组织剂量依赖性的氧化修饰(P<0.05)。结论1-BP暴露导致神经组织蛋白质氧化损伤,诱导UPS异常激活,可能是1-BP中毒性周围神经病发生的机制之一。Objective To study the effect of ubiquitin-proteasome system（ UPS） in 1-bromopropane（ 1-BP） induced peripheral neuropathy in rats. Methods A total of 30 male Wistar rats w ere randomly divided into 3 groups： control group,400 mg / kg·bw group（ low dose group）,and 800. All rats received an equal volume of corn oil and 1-BP（ dissolved in corn oil） once per day,5 days per week,for 16 consecutive weeks. Trypsin-like,chymotrypsin-like and peptide-glutamyl peptide hydrolase（ PGPH）-like proteinase activities w ere measured w ith fluorescence labeling method.The 4-HNE,M DA protein adducts level and 4-HNE protein adducts in vitro in different nerve tissues w ere detected w ith Western blotting. Results Compared w ith control group,the trypsin-like proteinase activity in sciatic nerve w as significantly elevated in the low and high dose groups（ P〈0. 01）; chymotrypsin-like proteinase activity in cerebrum in the high dose group w as markedly improved（ P〈0. 01）; PGPH-like proteinase activity in the cerebrum and sciatic nerve in the high dose group w as remarkably increased（ P〈0. 05）; 4-HNE and M DA protein adducts levels in sciatic nerve in the low dose group w ere increased（ P〈0. 01）; 4-HNE and M DA protein adducts levels in cerebrum and sciatic nerve in the high dose group w ere increased（ P〈0. 01）; 1-BP promoted the 4-HNE induced oxidative modification in cerebrum,spinal cord and sciatic nerve tissue in a dose-dependent manner（ P〈0. 05）. Conclusion 1-BP exposure resulted in the oxidative damaged proteins in the nervous system,and further abnormal activation of UPS,w hich might be involved in1-BP induced peripheral neuropathy.

关 键 词：1-溴丙烷 泛素蛋白酶体系统 周围神经病 4-羟基壬烯醛 丙二醛 

分 类 号：R994.6[医药卫生—毒理学]