蛋白酶体活性升高在1-BP致大鼠周围神经损伤中的作用

doi:10.6040/j.issn.1671-7554.0.2015.872

摘要/Abstract

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。

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

Abstract: 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 were 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 were measured with fluorescence labeling method. The 4-HNE, MDA protein adducts level and 4-HNE protein adducts in vitro in different nerve tissues were detected with Western blotting. Results Compared with control group, the trypsin-like proteinase activity in sciatic nerve was significantly elevated in the low and high dose groups(P<0.01); chymotrypsin-like proteinase activity in cerebrum in the high dose group was markedly improved(P<0.01); PGPH-like proteinase activity in the cerebrum and sciatic nerve in the high dose group was remarkably increased(P<0.05); 4-HNE and MDA protein adducts levels in sciatic nerve in the low dose group were increased(P<0.01); 4-HNE and MDA protein adducts levels in cerebrum and sciatic nerve in the high dose group were 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, which might be involved in 1-BP induced peripheral neuropathy. 山东大学学报 (医学版)54卷4期 -杨俊林,等.蛋白酶体活性升高在1-BP致大鼠周围神经损伤中的作用 \=-

Key words: 1-Bromopropane, Peripheral neuropathy, 4-Hydoxy-2-Nonenal, Malondialdehyde, Ubiquitin-proteasome system

中图分类号:

R994.6

杨俊林,王清华,王增金,赵秀兰. 蛋白酶体活性升高在1-BP致大鼠周围神经损伤中的作用[J]. 山东大学学报（医学版）, 2016, 54(4): 78-83.

YANG Junlin, WANG Qinghua, WANG Zengjin, ZHAO Xiulan. Elevated proteasomal activities in rats peripheral nervous system exposed to 1-Bromopropane[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(4): 78-83.

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