目的探讨蛋白激酶A（PKA）、蛋白激酶C（PKC）和细胞周期依赖性蛋白激酶5（CDK5）对2，5-己二酮（HD）中毒性周围神经病神经丝（NF）变化的作用。方法将30只体重为200～240g的SPF级雄性Wistar大鼠随机分为3组（1个对照组、2个染毒组），每组10只。经腹腔染毒HD，剂量分别为200和400mg/kg，每周染毒5d，每日1次，连续8周，建立HD中毒性神经病模型。对照组给予相同体积的生理盐水。利用SDS.PAGE和WesternBlotting方法检测脊髓胞浆蛋白和膜蛋白组分中PKA、PKC、P35前体和CDK5的相对含量。结果在脊髓胞浆蛋白组分中，与对照组比较，PKA和PKC含量在400mg/kg染毒组大鼠分别升高了46.1%和23.0%（P<0.01），而在200mg/kg染毒组均无明显改变（P>0.05）；p35前体和CDK5在200mg/kg染毒组分别升高了56.8%（P<0.01）和78.2%（P<0.01），而在400mg/kg染毒组，仅CDK5升高了21.9%（P<0.01），p35前体含量无明显改变。在脊髓膜蛋白组分中，PKA和CDK5含量在200、400mg/kg染毒组大鼠分别升高了19.3%（P<0.01），25.5%（P<0.01）和26.3%（P<0.01），12.7%（P<0.01）；PKC含量仅在400mg/kg染毒组升高了13.9%（P<0.01），而在200mg/kg染毒组无明显改变（P>0.05）；染毒组p35前体与对照组比较，变化不明显（P>0.05）。结论HD使脊髓组织中PKA、PKC和CDK5含量明显升高，提示相关蛋白激酶含量的升高可能是HD中毒性周围神经病的发病机

目的探讨大蒜油对2，5-己二酮（2，5-hexanedione，2，5-HD）导致的大鼠神经组织氧化损伤的拮抗作用和对周围运动神经毒性的影响。方法Wistar雄性大鼠40只，随机分为正常对照组、模型组、人蒜油低、高剂量组，每组10只。模型组及大蒜油低、高剂量组分别给予2，5。HD300ms/ks腹腔注射，正常对照组给予生理盐水，5次/周，持续6周。大蒜油低、高剂量组提前1周分别给予40和80mg/kg大蒜油灌胃，持续至实验结束。测定后肢撑力指数和平衡指数等神经行为学指标，实验结束取脑、脊髓和坐骨神经分别测定丙二醛（MDA）、还原型谷胱廿肽（GSH）含量、总抗氧化能力（T-AOC）和抑制羟自由基能力。结果与第0周比较，后肢撑力指数第4周模型组升高44%，大蒜油低剂量组升高50%，大蒜油高剂茸组升高49%，但3组间差异无统计学意义（P>0.05）；第4周模型组平衡指数降低30%，大蒜油低剂量组降低45%，大蒜油高剂量组降低68%，与模型组相比，差异有统计学意义（P<0.01）。大蒜油低、高剂基组大鼠在第4周即出现运动异常，较模型组人鼠提前l周；各组步态评分，模型组，大蒜油低、高剂量组均明显高于对照组，且大蒜油高剂量组高于模型组，差异均有统计学意义（P<0.05）。在大脑、脊髓和坐骨神经中，与正常对照组相比，模型组人鼠MDA含量升高，抑制羟自由基能力降低，差异均有统计学意义（P<0.05或P<0.01）；与模型组比较，大蒜油低、高剂最组在各神经组织中MDA含量均明显降低，抑制羟自由基能力明显升高，差异均有统计学意义（P<0.01）。结论大蒜油可拮抗2，5-HD所致的大鼠神经组织氧化损伤，但并末改善2，5-HD导致的周围运动神经损伤，提示氧化-抗氧化损伤不是2，5-HD中毒性神经病的主要机制。

Calcium-dependent mechanisms, particularly those mediated by Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII), have been implicated in neurotoxicant-induced neuropathy. However, it is unknown whether similar mechanisms exist in 2,5-hexanedione (HD)-induced neuropathy. For that, we investigated the changes of CaM, CaMKII, protein kinase C (PKC) and polymerization ratios (PRs) of NF-L, NF-M and NF-H in cerebral cortex (CC, including total cortex and some gray), spinal cord (SC) and sciatic nerve (SN) of rats treated with HD at a dosage of 1.75 or 3.50mmol/kg for 8 weeks (five times per week). The results showed that CaM contents in CC, SC and SN were significantly increased, which indicated elevation of Ca2+ concentrations in nerve tissues. CaMKII contents and activities were also increased in CC and were positively correlated with gait abnormality, but it could not be found in SC and SN. The increases of PKC contents and activities were also observed in SN and were positively correlated with gait abnormality. Except for that of NF-M in CC, the PRs of NF-L, NF-M and NF-H were also elevated in nerve tissues, which was consistent with the activation of protein kinases. The results suggested that CaMKII might be partly (in CC but not in SC and SN) involved in HD-induced neuropathy. CaMKII and PKC might mediate the HD neurotoxicity by altering the NF phosphorylation status and PRs.

To investigate the reversibility of the neuropathy induced by 2,5-HD, adult male rats were administered at a dosage of 400 mg/kg/day 2,5-HD (five times per week) for 2, 4, and 8 weeks, respectively. After stopping HD exposure, half of 8-week treated animals were allowed to naturally recover for 16 weeks. The relative levels of NF-H, NF-M, and NF-L in spinal cords and sciatic nerves of rats were determined by immunoblotting during the HD neuropathy. The results showed that NFs content in nerve tissues demonstrated a progressive decline as the intoxication continued. Furthermore, after a recovery of 16 weeks, the levels of three NF subunits in spinal cords of treated rats returned to normal while those in sciatic nerves displayed an inconsistent reversal. Among them, the level of NF-H in sciatic nerves returned to normal completely, and NF-L also showed a significant improvement, whereas NF-Mdid not demonstrate an obvious reversal. These findings suggest that HD-induced NFs decline is at least partially irreversible within the time frame of this study, which might be associated with the incomplete recovery of neurological dysfunctions of HD-treated rats.