Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Eur J Clin Invest. 2011 Apr;41(4):442-50. doi: 10.1111/j.1365-2362.2010.02430.x. Epub 2010 Dec 3.
Methyl-base-attached cobalamin (Methycobalamin) (MC) has a special affinity for nerve tissues to promote myelination and transport of axonal cytoskeleton. It is not known, however, how MC influences on peripheral nerve in experimental diabetic neuropathy.
We studied the effects of MC on expressions and activities of protein kinase C (PKC) in peripheral nerve of streptozotocin-induced diabetic rats. Wistar rats, 8 weeks of age, were rendered diabetic by streptozotocin (40 mg kg(-1), iv) and followed for 16 weeks. A half of diabetic animals were treated with MC (10 mg kg(-1) per every other day, im) after the induction of diabetes. Normal Wistar rats were served as control.
At the end, untreated diabetic animals developed significant delay of nerve conduction velocity (NCV), and MC treatment normalized the NCV. Nerve PKC activity was significantly suppressed in untreated diabetic rats, while the activity was normalized in treated animals. While PKCα located in Schwann cells, PKCβΙα and βII distributed in axoplasm, vascular walls and macrophages. The decreased PKC activity in diabetic nerve was associated with reduced expression of membrane PKCα and increased membrane expression of PKCβII, and MC treatment corrected these changes. Diabetic nerve contained an increased number of macrophages and 8-hydroxydeoxyguanosine-positive cells in the endoneurium, the latter of which was significantly suppressed by MC treatment. Elevated nerve polyol levels in diabetic nerve were partially corrected by MC treatment.
This study suggested that correction of impaired neural signalling of PKC and oxidative stress-induced damage may be a major attribute to the beneficial effects of MC on diabetic nerve.
甲基钴胺素（Methycobalamin，MC）通过与甲基结合，具有特殊的神经组织亲和力，可促进髓鞘形成和轴突细胞骨架的运输。然而，MC 如何影响实验性糖尿病周围神经病变中的周围神经尚不清楚。
我们研究了 MC 对链脲佐菌素诱导的糖尿病大鼠周围神经蛋白激酶 C（PKC）表达和活性的影响。8 周龄 Wistar 大鼠经链脲佐菌素（40mg/kg，iv）诱导糖尿病，随后随访 16 周。一半糖尿病动物在糖尿病诱导后每隔一天接受 MC（10mg/kg，im）治疗。正常 Wistar 大鼠作为对照。
未治疗的糖尿病动物在实验结束时出现明显的神经传导速度（NCV）延迟，而 MC 治疗使 NCV 正常化。未治疗的糖尿病大鼠神经 PKC 活性显著受到抑制，而治疗动物的 PKC 活性则正常化。PKCα位于施万细胞中，PKCβΙα和βII 分布在轴突、血管壁和巨噬细胞中。糖尿病神经中 PKC 活性的降低与膜 PKCα表达减少和膜 PKCβII 表达增加有关，MC 治疗纠正了这些变化。糖尿病神经内有大量巨噬细胞和 8-羟基脱氧鸟苷阳性细胞，后者被 MC 治疗显著抑制。MC 治疗部分纠正了糖尿病神经中升高的多醇水平。
本研究表明，纠正 PKC 神经信号受损和氧化应激诱导的损伤可能是 MC 对糖尿病神经有益作用的主要原因。
