外源性糖基化终产物诱导大鼠神经病变。
Neuropathy induced by exogenously administered advanced glycation end-products in rats.
机构信息
Department of Pathology and Molecular Medicine, Graduate School of Medicine, Hirosaki University, Hirosaki.
Division of Neurology, Aomori Prefectural Hospital, Aomori.
出版信息
J Diabetes Investig. 2010 Apr 22;1(1-2):40-9. doi: 10.1111/j.2040-1124.2009.00002.x.
UNLABELLED
Aims/Introduction: Advanced glycation end-products (AGE) have been implicated in the development of diabetic neuropathy. It still remains unknown, however, how AGE cause functional and structural changes of the peripheral nerve in diabetes. To explore the role of AGE in diabetic neuropathy, we examined the peripheral nerve by injecting AGE into normal Wistar rats.
MATERIALS AND METHODS
Young, normal male Wistar rats were injected intraperitoneally (i.p.) daily for 12 weeks with purified AGE prepared by incubating D-glucose with bovine serum albumin (BSA). A control group received BSA alone. A group of rats given AGE were co-treated with aminoguanidine (50 mg/kg/day, i.p.). Peripheral nerve function and structure, as well as nerve Na(+),K(+)-ATPase activity, were examined in these rats. Immunohistochemical expressions of 8-hydroxy-2'-deoxyguanosine (8OHdG) and nuclear factor-κB (NF-κB)p65 were also examined.
RESULTS
Serum AGE levels were increased two to threefold in the AGE-treated group compared with those in the BSA-treated control group. AGE-treated rats showed a marked slowing of motor nerve conduction velocity (MNCV) and decreased nerve Na(+),K(+)-ATPase activity compared with those in the BSA-treated group. These changes were accompanied by intensified expressions of 8OHdG and NF-κBp65 in endothelial cells and Schwann cells. Aminoguanidine treatment corrected MNCV delay, Na(+),K(+)-ATPase activity, and suppressed the expression of 8OHdG and NF-κB, despite there being no influence on serum AGE levels.
CONCLUSIONS
The results suggest that an elevated concentration of blood AGE might be one of the contributing factors to the development of neuropathic changes in diabetes.
目的/引言：晚期糖基化终产物（AGE）与糖尿病性神经病的发生有关。然而，AGE 如何引起糖尿病患者周围神经的功能和结构变化仍不清楚。为了探讨 AGE 在糖尿病性神经病中的作用，我们向正常 Wistar 大鼠的腹腔内注射 AGE 来研究外周神经。
材料和方法
年轻的正常雄性 Wistar 大鼠每天腹腔内注射纯化的 AGE 12 周，AGE 由孵育 D-葡萄糖和牛血清白蛋白（BSA）制成。对照组给予 BSA 单独处理。一组给予 AGE 的大鼠用氨基胍（50mg/kg/天，腹腔内注射）进行联合治疗。这些大鼠的周围神经功能和结构以及神经 Na(+)，K(+) -ATP 酶活性也进行了检查。还检查了 8-羟基-2'-脱氧鸟苷（8OHdG）和核因子-κB（NF-κB）p65 的免疫组织化学表达。
结果
与 BSA 处理的对照组相比，AGE 处理组的血清 AGE 水平增加了两到三倍。与 BSA 处理组相比，AGE 处理组的运动神经传导速度（MNCV）明显减慢，神经 Na(+)，K(+) -ATP 酶活性降低。这些变化伴随着内皮细胞和施万细胞中 8OHdG 和 NF-κBp65 的表达增强。尽管对血清 AGE 水平没有影响，但氨基胍治疗纠正了 MNCV 延迟、Na(+)，K(+) -ATP 酶活性，并抑制了 8OHdG 和 NF-κB 的表达。
结论
这些结果表明，血液 AGE 浓度升高可能是糖尿病神经病变发生的原因之一。
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