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目的观察加巴喷丁(GBP)对糖尿病神经痛(PDN)大鼠皮肤机械痛敏和脊髓谷氨酸(Glu)含量及下丘脑c-Jun氨基末端蛋白激酶(JNK)的动态表达,探讨GBP在PDN治疗方面的作用机制。方法制作链脲佐菌素(STZ)PDN大鼠模型。随机分为对照组、PDN组和GBP组。GBP组给予GBP干预,1次/d,按100 mg/kg,连续14d,灌胃给药。对照组大鼠不做任何处理,实验期间各组大鼠均隔天测定机械痛阈一次。实验结束后采用OPA柱前衍生高效液相色谱法测定各组大鼠L5-DRG,L6-DRG和脊髓组织及脊髓微透析液中Glu含量,免疫组化SP法观察大鼠下丘脑JNK动态表达。结果实验观察期内GBP组痛觉阈值稳中有升,PDN组痛觉阈值呈现进行性下降,较GBP组差异有统计学意义(P<0.05)。Glu在各实验组大鼠L5-DRG、L6-DRG、脊髓组织和脊髓微透析液中含量不同,GBP组脊髓组织和脊髓微透析液中Glu含量低于PDN组(P<0.01);L5-DRG,L6-DRG中Glu含量高于PDN组(P<0.05)。JNK在PDN组大鼠下丘脑视上核、室周核和弓状核的表达量均高于GBP组(P<0.05),也高于对照组(P<0.01)。结论 GBP具有减轻PDN大鼠皮肤机械痛敏的作用,其作用机制可能与抑制脊髓兴奋性氨基酸神经递质Glu的释放及下丘脑JNK的动态表达密切相关。
Objective To observe the effects of gabapentin (DF) on the skin mechanical pain and glutamate (Glu) content of diabetic neuralgia (PDN) rats and the dynamic expression of c-Jun N-terminal kinase (JNK) in hypothalamus. The mechanism of action. Methods Streptozotocin (STZ) PDN rat model was established. Randomly divided into control group, PDN group and GBP group. GBP group was given GBP intervention, 1 time / d, according to 100 mg / kg, continuous 14d, intragastric administration. The control group rats did not do any treatment, during the experiment, rats in each group were measured mechanical pain threshold every other day. After the experiment, the content of Glu in L5-DRG, L6-DRG, spinal cord tissue and spinal microdialysis fluid in each group was determined by OPA pre-column derivatization high performance liquid chromatography. The dynamic expression of JNK in hypothalamus was observed by immunohistochemistry . Results In the experimental period, the pain threshold of GBP group increased steadily and the pain threshold of PDN group showed a progressive decrease, which was significantly different from that of GBP group (P <0.05). Glu content in L5-DRG, L6-DRG, spinal cord tissue and spinal microdialysis fluid in each experimental group was different. Glu content in spinal cord tissue and spinal microdialysate in GBP group was lower than that in PDN group (P <0.01) The content of Glu in DRG and L6-DRG was higher than that in PDN group (P <0.05). The expression of JNK in the hypothalamic supraoptic nucleus, periventricular nucleus and arcuate nucleus in PDN group was higher than that in GBP group (P <0.05) and also higher than that in control group (P <0.01). CONCLUSION: GBP has the effect of reducing the mechanical hyperalgesia in the skin of PDN rats. Its mechanism may be related to inhibiting the release of Glu, an excitatory amino acid neurotransmitter, and the dynamic expression of JNK in hypothalamus.