CAJ | 학술논문

目的探讨细胞周期依赖性蛋白激酶5(CDK5)在2,5-己二酮(HD)中毒性周围神经病发病过程中的作用.方法 30只雄性Wistar大鼠,随即分为对照组、200mg/kg HD染毒组和400mg/kg HD染毒组,每组10只.染毒途径为腹腔注射,每周5次,连续8周,建立HD中毒性神经病模型.利用Western blotting方法检测大脑、脊髓和坐骨神经胞浆蛋白和膜蛋白中CDK5、p35和p25的相对含量.结果与对照组相比,P35蛋白含量在200、400mg/kg HD染毒大鼠大脑和脊髓胞浆蛋白组分中明显降低,而在脊髓和坐骨神经膜蛋白组分中含量明显升高,差异均有统计学意义(P＜0.01);p25变化趋势与p35基本一致.CDK5在200、400mg/kg HD染毒大鼠大脑胞浆和膜蛋白中均明显下降;除坐骨神经膜蛋白组分中未检出外,在脊髓和坐骨神经中CDK5含量明显升高,与对照组比较,差异有统计学意义(P＜0.01).结论 HD中毒后大鼠神经组织中CDK5及其激活因子p35和p25发生明显改变,这种改变可能与HD中毒性周围同神经病的发病机制有关.
목적 탐토세포주기의뢰성단백격매5(CDK5)재2,5-기이동(HD)중독성주위신경병발병과정중적작용.방법 30지웅성Wistar대서,수즉분위대조조、200mg/kg HD염독조화400mg/kg HD염독조,매조10지.염독도경위복강주사,매주5차,련속8주,건립HD중독성신경병모형.이용Western blotting방법검측대뇌、척수화좌골신경포장단백화막단백중CDK5、p35화p25적상대함량.결과 여대조조상비,P35단백함량재200、400mg/kg HD염독대서대뇌화척수포장단백조분중명현강저,이재척수화좌골신경막단백조분중함량명현승고,차이균유통계학의의(P＜0.01);p25변화추세여p35기본일치.CDK5재200、400mg/kg HD염독대서대뇌포장화막단백중균명현하강;제좌골신경막단백조분중미검출외,재척수화좌골신경중CDK5함량명현승고,여대조조비교,차이유통계학의의(P＜0.01).결론 HD중독후대서신경조직중CDK5급기격활인자p35화p25발생명현개변,저충개변가능여HD중독성주위동신경병적발병궤제유관.
Objective To explore the role of cyclin dependent kinase 5 (CDK5) in 2, 5-hexanedione (HD)-induced neuropathy. Methods Thirty male Wistar rats weighted 200～240g were divided randomly into three groups, i. e. control group, 200mg/kg HD group and 400mg/kg HD group (n=10 for each group). HD was administered to rats by intraperitoneal injection at dosage of 200 or 400mg/kg for 8 weeks (five times per week) to establish the intoxicated rats model. The relative contents of CDK5, p35 and p25 were determined in cerebrum, spinal cord and sciatic nerve of rats by Western Blotting. Results Compared with that of the control group rats, p35 contents were significantly decreased (P＜0.01) in the cytosolic fractions of cerebrum and spinal cord in both the 200 and 400 mg/kg HD intoxicated rats, while in the membrane fractions of spinal cord and sciatic nerve, p35 contents were increased significantly (P＜0.01). The changes of p25 showed the same pattern with p35. P25 contents were significantly reduced (P＜0.05) in the cytosolic (cerebrum and spinal cord) and membrane (cerebrum) fractions of both HD-treated rats and were elevated (P＜0.01) in the membrane fraction of spinal cord and cytosolic fraction of sciatic nerve. The relative amounts of CDK5 were significantly decreased (P＜0.01) in the cytosolic and membrane fractions of cerebrum in both the 200 and 400mg/kg HD intoxicated rats. Except for membrane fraction of sciatic nerve, the significant increased (P＜0.01) of CDK5 were observed in the spinal cord and sciatic nerve of both the 200 and 400mg/kg HD treated rats. Conclusion HD can induce significant changes of CDK5 and its activators p35, p25 in nerve tissues, which may be related to the neuropathy induced by HD.