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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 investigate the role of ubiquitin proteasome system (UPS) in peripheral neuropathy induced by 1-bromopropane (1-BP) in rats. Methods Thirty male Wistar rats were randomly divided into control group, 400 mg / kg · bw group (low dose group) and 800 mg / kg · bw group (high dose group), and were orally administered with equal volume of corn oil and 1 -BP (dissolved in corn oil) once daily for 5 days per week for 16 weeks. The activity of tryptase, chymotrypsin and peptide-glutamyl peptidase (PGPH) in different nerve tissues of rats was detected by fluorescence detection method. The content of 4-hydroxynonenal in different nerve tissues of rats 4-HNE) and malondialdehyde (MDA) protein adducts, and the promoting effect of 1-BP on 4-HNE oxidatively modified nerve tissue protein in vitro. Results Compared with the control group, the trypsin activity of the sciatic nerve increased (P <0.01) in the low and high dose groups, and increased in the high dose group (P <0.01). The activity of PGPH in the brain and sciatic nerve increased (P <0.05). Compared with the control group, the expression of 4-HNE and MDA protein adducts increased in the sciatic nerve tissue of the low-dose group (P <0.01). The levels of 4-HNE and MDA in the brain and sciatic nerve of high- 1-BP promoted the dose-dependent oxidative modification of brain, spinal cord and sciatic nerve tissue by 4-HNE (P <0.05). Conclusion 1-BP exposure leads to the oxidative damage of nerve tissue protein and induces abnormal activation of UPS, which may be one of the mechanisms of 1-BP toxic peripheral neuropathy.