Diemel L T, Brewster W J, Fernyhough P, Tomlinson D R
Department of Pharmacology, Faculty of Basic Medical Sciences, Queen Mary and Westfield College, London, UK.
Brain Res Mol Brain Res. 1994 Jan;21(1-2):171-5. doi: 10.1016/0169-328x(94)90391-3.
Rats with streptozotocin-induced diabetes of 4 to 6 weeks duration showed a depletion of both substance P (P < 0.01) and calcitonin gene-related peptide (P < 0.01) in the sciatic nerve. Since expression of both peptides is sensitive to nerve growth factor (NGF) in vitro we examined the effect of treatment of diabetic rats with NGF, which significantly increased the levels of both peptides in treated diabetic animals (P < 0.01 for both). Treatment of non-diabetic rats with a similar NGF regime raised the mean peptide levels to a value similar to that seen in treated diabetic rats but the change was not statistically significant. In vehicle-treated diabetic rats the depletions of sciatic nerve neuropeptides were accompanied by a significant (P < 0.05) reduction in the level of CGRP mRNA in the 4th and 5th lumbar dorsal root ganglia, this was accompanied by an analogous reduction in the mRNA for gamma-preprotachykinin A (gamma-PPT), which did not attain statistical significance. Treatment of diabetic rats with NGF also prevented the deficits in the levels of CGRP and gamma-PPT mRNA in the lumbar dorsal root ganglia (P < 0.05). Treatment of other diabetic rats with the related neurotrophin, brain-derived neurotrophic factor (BDNF), had no effect on the levels of substance P and calcitonin gene-related peptide in the sciatic nerve.
患有链脲佐菌素诱导的糖尿病达4至6周的大鼠，其坐骨神经中的P物质（P<0.01）和降钙素基因相关肽（P<0.01）均出现耗竭。由于这两种肽的表达在体外对神经生长因子（NGF）敏感，我们研究了用NGF治疗糖尿病大鼠的效果，结果显示在接受治疗的糖尿病动物中，这两种肽的水平均显著升高（两者P均<0.01）。用类似的NGF方案治疗非糖尿病大鼠，可使肽的平均水平升高至与接受治疗的糖尿病大鼠相似的值，但这种变化无统计学意义。在用赋形剂治疗的糖尿病大鼠中，坐骨神经神经肽的耗竭伴随着第4和第5腰段背根神经节中降钙素基因相关肽（CGRP）mRNA水平的显著降低（P<0.05），同时γ-前速激肽原A（γ-PPT）的mRNA也有类似程度的降低，但未达到统计学意义。用NGF治疗糖尿病大鼠还可预防腰段背根神经节中CGRP和γ-PPT mRNA水平的降低（P<0.05）。用相关神经营养因子脑源性神经营养因子（BDNF）治疗其他糖尿病大鼠，对坐骨神经中P物质和降钙素基因相关肽的水平没有影响。
