Evaluation of orally active poly(ADP-ribose) polymerase inhibitor in streptozotocin-diabetic rat model of early peripheral neuropathy
Evaluation of orally active poly(ADP-ribose) polymerase inhibitor in streptozotocin-diabetic rat model of early peripheral neuropathy
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DOI：
10.1007/s00125-004-1356-0
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发表时间：
2004-04-01
期刊：
影响因子：
8.2
通讯作者：
Obrosova, IG
中科院分区：
文献类型：
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作者：
Li, F;Szabó, C;Obrosova, IG
目的/假说。Poly（adp -核糖）聚合酶的激活消耗NAD（+）和高能磷酸盐，激活蛋白激酶C，并影响各种组织的基因表达。本研究旨在探讨口服有效的聚（adp -核糖）聚合酶抑制剂PJ34对早期糖尿病大鼠神经病模型的影响。对照组和链脲佐菌素糖尿病大鼠分别给予或不给予PJ34 (30 mg.kg（-1)day(-1)）治疗两周，然后不给药两周。通过氢清除率评估神经内膜血流量；用酶促荧光光谱法测定代谢产物和高能磷酸盐；免疫组织化学检测聚adp核糖。与对照组相比，未经治疗和pj34治疗的糖尿病大鼠血糖浓度升高的程度相似。糖尿病大鼠坐骨神经可见强烈的聚腺苷核糖免疫染色，而其他各组坐骨神经无明显的聚腺苷核糖免疫染色。糖尿病大鼠坐骨运动神经最终传导速度和指感神经最终传导速度分别比对照组降低24%和22% (p
Aims/hypothesis.. Poly(ADP-ribose) polymerase activation depletes NAD(+) and high-energy phosphates, activates protein kinase C, and affects gene expression in various tissues. This study was designed to characterise the effects of the potent, orally active poly(ADP-ribose) polymerase inhibitor PJ34 in the Wistar rat model of early diabetic neuropathy.Methods.. Control and streptozotocin-diabetic rats were maintained with or without PJ34 treatment (30 mg.kg(-1.)day(-1)) for two weeks, after two weeks without treatment. Endoneurial blood flow was assessed by hydrogen clearance; metabolites and high-energy phosphates were assayed by enzymatic spectrofluorometric methods; and poly(ADP-ribose) was detected by immunohistochemistry.Results.. Blood glucose concentrations were increased to a similar extent in untreated and PJ34-treated diabetic rats compared with controls. Intense poly(ADP-ribose) immunostaining was observed in the sciatic nerve of diabetic rats, but not in other groups. Final sciatic motor nerve conduction velocity and digital sensory nerve conduction velocity were reduced by 24% and 22% respectively in diabetic rats compared with controls (p