Stimulation of nerve growth factor and substance P expression in the iris-trigeminal axis of diabetic rats - Involvement of oxidative stress and effects of aldose reductase inhibition
Stimulation of nerve growth factor and substance P expression in the iris-trigeminal axis of diabetic rats - Involvement of oxidative stress and effects of aldose reductase inhibition
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DOI：
10.1016/s0006-8993(98)00638-6
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发表时间：
1998-08-17
期刊：
影响因子：
2.9
通讯作者：
Tomlinson, DR
中科院分区：
文献类型：
--
作者：
Fernyhough, P;Brewster, WJ;Tomlinson, DR
在链佐菌素诱导的糖尿病大鼠中，我们检测到虹膜中神经生长因子（NGF） mRNA增加（61%,P < 0.05），三叉神经节中P物质前体前原激肽（preprotachykinin） mRNA增加（82%,P < 0.05），表明NGF增加导致P物质基因表达增加。在其他糖尿病大鼠中，用抗氧化剂（丁基羟基甲苯；1%的饮食）或醛糖还原酶抑制剂（ARI）（山梨比尼；25mg /kg/day p.o）治疗可以预防这些变化，山梨比尼治疗与晶体和坐骨神经中多元醇途径中间体的显著抑制有关。这表明晶状体中多元醇途径的活性可能转化为虹膜中氧化应激驱动的NGF基因表达的刺激。这种变化对神经生长因子是选择性的，因为在相同的虹膜中，类似的神经营养因子神经营养因子-3 （NT-3）的表达没有改变。这些变化表明，氧化应激和/或炎症可以促进糖尿病中NGF的表达——这一机制可能参与虹膜炎。(C) 1998 Elsevier Science B.V.版权所有
In rats with streptozotocin-induced diabetes, we measured increased (by 61%; P < 0.05) mRNA for nerve growth factor (NGF) in the iris together with increased (by 82%; P < 0.05) mRNA for preprotachykinin (the substance P precursor) in the trigeminal ganglion, suggesting that increased NGF was driving increased substance P gene expression. In other diabetic rats, these changes were prevented by treatment with either an antioxidant (butylated hydroxytoluene; 1% by diet) or an aldose reductase inhibitor (ARI) (sorbinil; 25 mg/kg/day p.o.) and the sorbinil treatment was associated with significant inhibition of polyol pathway intermediates in both lens and sciatic nerve. This suggests that polyol pathway activity in the lens may translate to oxidative stress-driving stimulation of NGF gene expression in the iris. The change is selective for NGF, because expression of the analogous neurotrophin, neurotrophin-3 (NT-3), was unaltered in the same irises. These changes suggest that oxidative stress and/or inflammation can drive up NGF expression in diabetes-a mechanism that might participate in iritis. (C) 1998 Elsevier Science B.V. All rights reserved.