Garrett N E, Malcangio M, Dewhurst M, Tomlinson D R
Department of Pharmacology, St. Bartholomew's, Queen Mary and Westfield College, London, UK.
Neurosci Lett. 1997 Feb 7;222(3):191-4. doi: 10.1016/s0304-3940(97)13383-3.
This study compared the effects of treatment of diabetic rats with either alpha-lipoic acid (100 mg/kg/day i.p. 5 days/week) or with recombinant human nerve growth factor (rhNGF; 0.2 mg/kg s.c. 3 days/week) on NGF-like immunoreactivity (NGFLI) and neuropeptide Y-like immunoreactivity (NPYLI) levels in the sciatic nerve and on the release of substance P-like immunoreactivity (SPLI) from the spinal cord in response to electrical stimulation of the dorsal roots in vitro. Diabetic rats showed depletion of NGFLI and NPYLI, together with reduced release of SPLI. Treatment with NGF increased the sciatic nerve NGFLI (to four times that seen in untreated diabetic rats) and normalised stimulus-evoked release of SPLI, but did not affect the sciatic nerve NPYLI. Treatment with alpha-lipoic acid caused a small non-significant increase in sciatic nerve NGFLI, but normalised both NPYLI levels and stimulus-evoked release of SPLI. These findings indicate that alpha-lipoic acid can boost neurotrophic support in diabetic rats, with effects beyond those related to NGF.
本研究比较了用α-硫辛酸(100毫克/千克/天,腹腔注射,每周5天)或重组人神经生长因子(rhNGF;0.2毫克/千克,皮下注射,每周3天)治疗糖尿病大鼠,对坐骨神经中神经生长因子样免疫反应性(NGFLI)和神经肽Y样免疫反应性(NPYLI)水平,以及对体外电刺激背根时脊髓中P物质样免疫反应性(SPLI)释放的影响。糖尿病大鼠表现出NGFLI和NPYLI减少,同时SPLI释放降低。用NGF治疗可增加坐骨神经NGFLI(增至未治疗糖尿病大鼠的四倍),并使刺激诱发的SPLI释放正常化,但不影响坐骨神经NPYLI。用α-硫辛酸治疗使坐骨神经NGFLI有小幅但无统计学意义的增加,但使NPYLI水平和刺激诱发的SPLI释放均正常化。这些发现表明,α-硫辛酸可增强糖尿病大鼠的神经营养支持,其作用超出了与NGF相关的作用。