氨基胍——对正常及链脲佐菌素诱导的糖尿病大鼠神经内膜血管活性一氧化氮及运动神经传导速度的影响

Aminoguanidine--effects on endoneurial vasoactive nitric oxide and on motor nerve conduction velocity in control and streptozotocin-diabetic rats.

作者信息

Dewhurst M, Omawari N, Tomlinson D R

机构信息

Department of Pharmacology, St. Bartholomew's, London.

出版信息

Br J Pharmacol. 1997 Feb;120(4):593-8. doi: 10.1038/sj.bjp.0700946.

DOI:10.1038/sj.bjp.0700946

PMID:9051296

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1564506/

Abstract

The effects of aminoguanidine (AG) treatment on reductions in motor nerve conduction velocity (MNCV) and sciatic nerve blood flow, indexed by laser Doppler flux (LDF), were investigated in rats with experimental diabetes (streptozotocin-induced; 8-10 weeks duration). The contribution of endoneurial vasoactive nitric oxide to the LDF of these animals was also investigated by the direct micro-injection of NG-nitro-L-arginine methyl ester (L-NAME; 1 nmol in 1 microliter), followed by L-arginine (100 nmol in 1 microliter), into the sciatic nerve endoneurium. 2. The MNCV (m s-1, mean +/- 1 s.d.) of diabetic rats (38.2 +/- 1.5) was lower (P < 0.01) than that of age-matched controls (47.2 +/- 4.2). AG treatment (50 mg kg-1 day-1, i.p.) attenuated the diabetes-induced deficits in MNCV (43.4 +/- 5.9; P < 0.01), but had no effect in controls (48.8 +/- 3.8) or, if administered via drinking water (1 gl-1), diabetics (37.4 +/- 4.1). 3. L-NAME markedly reduced the resting LDF (arbitrary units; mean +/- s.e.mean) of controls (209 +/- 13 to 120 +/- 18; P < 0.005), an effect reversed by subsequent L-arginine (to 206 +/- 27). In diabetic rats the LDF reduction following L-NAME was much smaller (111 +/- 11 to 84 +/- 6; P < 0.05), but the change with L-arginine was significantly increased (to 145 +/- 12; P < 0.001). 4. AG treatment increased the resting LDF of control (265 +/- 34) and diabetic rats (133 +/- 14 for daily injection and 119 +/- 13 for drinking water). The responses to L-NAME and L-arginine were not changed markedly by AG treatment. However, L-arginine appeared to be less effective. 5. In conclusion, these data suggest that AG treatment may affect nitric oxide production in the vasa nervorum of peripheral nerves. However, the effects of AG-treatment are not consistent with the prevention of a diabetes-associated reduction in endoneurial nitric oxide production. The mechanisms by which AG attenuates nerve conduction slowing in streptozotocin-diabetic rats therefore remain unclear.

摘要

在实验性糖尿病大鼠（链脲佐菌素诱导，病程8 - 10周）中，研究了氨基胍（AG）治疗对运动神经传导速度（MNCV）降低以及以激光多普勒血流（LDF）为指标的坐骨神经血流的影响。还通过将NG - 硝基 - L - 精氨酸甲酯（L - NAME；1微升含1纳摩尔），随后再注入L - 精氨酸（1微升含100纳摩尔）直接微量注射到坐骨神经内膜，研究了神经内膜血管活性一氧化氮对这些动物LDF的作用。2. 糖尿病大鼠的MNCV（米/秒，平均值±1标准差）为38.2±1.5，低于年龄匹配对照组（47.2±4.2，P < 0.01）。AG治疗（腹腔注射，50毫克/千克/天）减轻了糖尿病引起的MNCV降低（43.4±5.9；P < 0.01），但对对照组（48.8±3.8）无影响，若通过饮用水（1克/升）给药，对糖尿病大鼠也无影响（37.4±4.1）。3. L - NAME显著降低了对照组的静息LDF（任意单位；平均值±标准误平均值）（从209±13降至120±18；P < 0.005），随后的L - 精氨酸可逆转此效应（升至206±27）。在糖尿病大鼠中，L - NAME后的LDF降低幅度小得多（从111±11降至84±6；P < 0.05），但L - 精氨酸引起的变化显著增加（升至145±12；P < 0.001）。4. AG治疗增加了对照组（265±34）和糖尿病大鼠的静息LDF（每日注射组为133±14，饮用水给药组为119±13）。AG治疗对L - NAME和L - 精氨酸的反应无明显改变。然而，L - 精氨酸似乎效果较差。5. 总之，这些数据表明AG治疗可能影响周围神经血管中一氧化氮的产生。然而，AG治疗的效果与预防糖尿病相关的神经内膜一氧化氮产生减少不一致。因此，AG减轻链脲佐菌素诱导的糖尿病大鼠神经传导减慢的机制仍不清楚。