Methylcobalamin effects on diabetic neuropathy and nerve protein kinase C in rats
Methylcobalamin effects on diabetic neuropathy and nerve protein kinase C in rats
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DOI：
10.1111/j.1365-2362.2010.02430.x
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发表时间：
2011-04-01
影响因子：
5.5
通讯作者：
Yagihashi, Soroku
中科院分区：
文献类型：
--
作者：
Mizukami, Hiroki;Ogasawara, Saori;Yagihashi, Soroku
甲基钴胺素（Methycobalamin，MC）对神经组织具有特殊的亲和力，可促进髓鞘形成和轴突细胞骨架的转运。MC对糖尿病大鼠周围神经蛋白激酶C（protein kinase C，PKC）表达和活性的影响。Wistar大鼠，8周龄，糖尿病链脲佐菌素（40毫克kg-1，静脉注射），并随后为16周。糖尿病动物中的一半在诱导糖尿病后用MC（10 mg·kg ~（-1），每隔一天，im）治疗。正常Wistar大鼠作为control.ResultsAt结束时，未经治疗的糖尿病动物神经传导速度（NCV）显着延迟，和MC治疗正常化的NCV。神经PKC活性显着抑制在未经治疗的糖尿病大鼠，而活动正常化治疗的动物。PKC α位于施万细胞中，PKC β α和β II分布在轴浆、血管壁和巨噬细胞中。糖尿病神经中PKC活性的降低与膜PKC α表达的降低和膜PKC β II表达的增加有关，MC治疗纠正了这些变化。糖尿病神经含有大量的巨噬细胞和8-羟基脱氧鸟苷阳性细胞的神经内膜，后者被MC治疗显着抑制。升高的神经多元醇水平在糖尿病神经部分纠正MC treatment.ConclusionsThis研究表明，纠正受损的PKC和氧化应激引起的损伤的神经信号可能是一个主要的属性MC对糖尿病神经的有益影响。
P>BackgroundMethyl-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.Materials and methodsWe 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.ResultsAt 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 PKC alpha located in Schwann cells, PKC beta alpha and beta II distributed in axoplasm, vascular walls and macrophages. The decreased PKC activity in diabetic nerve was associated with reduced expression of membrane PKC alpha and increased membrane expression of PKC beta II, 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.ConclusionsThis 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.