吡哆胺与辛伐他汀对糖尿病大鼠神经病理性疼痛的影响及内分泌调控意义  

Effects of pyridoxamine and simvastatin on neuropathic pain in diabetic rats and the significance of endocrine regulation

作　　者：吕春凤 LV Chun-feng(Tianjin Beichen hospital,Tianjin 300400,China)

机构地区：[1]天津市北辰医院,天津300400

出　　处：《吉林医学》2022年第6期1445-1449,共5页Jilin Medical Journal

摘　　要：目的:分析吡哆胺和辛伐他汀在糖尿病神经病理性疼痛(DNP)的大鼠给药治疗中的应用效果及内分泌因子的表达。方法:选取40只雄性SD大鼠作为研究对象,将其中30只构建为糖尿病大鼠模型,根据给药方式的不同分为D0组(正常对照)、D1组(给予吡哆胺)、D2组(给予辛伐他汀)、D3组(无菌水)。电子测痛仪检测大鼠机械刺激缩足反射阈值(PWMT),热辐射刺激仪检测大鼠热刺激缩足反射潜伏期(PWTL),免疫荧光染色检测星形胶质细胞的晚期糖基化终产物受体(RAGE)和p-NF-kB蛋白表达,免疫组化染色检测纤维细胞生长因子2(FGF-2)水平。结果:D3组大鼠PWMT、PWTL 1周内随时间推移而明显下降,显著低于D0、D1、D2组,差异有统计学意义(P<0.05);D3组大鼠RAGE、p-NF-κB蛋白阳性表达率明显高于D1、D2组,差异有统计学意义(P<0.05),D1组和D2组大鼠RAGE、p-NF-κB蛋白阳性表达率比较,差异无统计学意义(P>0.05)。D3组大鼠FGF-2蛋白PU值高于D0、D1、D2、D3组,差异有统计学意义(P<0.05),D1、D2组FGF-2蛋白PU值比较,差异无统计学意义(P>0.05)。结论:内分泌因子FGF-2参与了大鼠神经病理疼痛的产生和维持。吡哆胺和辛伐他汀能够通过抑制RAGE、p-NF-κB的激活及FGF-2蛋白的表达,来有效减轻糖尿病大鼠的机械痛敏及热阈痛,且改善效果相近。Objective To analyse the application effects of pyridoxamine and simvastatin in the drug treatment of Sprague-Dawley(SD)rats with diabetic neuropathic pain(DNP)and the expression of endocrine factors.Method 40 male rats were selected as the subjects investigated,and 30 of them were constructed as diabetic rat models.Based on different administration methods,all the male rats were grouped into D0 group(a normal control),D1 group(a pyridoxamine),D2 group(a simvastatin),and D3 group(a sterile water),respectively.Electric VonFrey and thermal radiation stimulator were applied to detect the paw withdrawal mechanical threshold(PWMT)and paw withdrawal thermal latency(PWTL)of rats,respectively.The immunofluorescence staining was employed to detect the expressions of receptor for advanced glycation end-products(RAGE)and phosphor-nuclear factor-kappa B(p-NF-kB)protein in astrocytes.In addition,fibroblast growth factor 2(FGF-2)levels were detected by immunohistochemical staining.Results The PWMT and PWTL of rats in the D3 group decreased significantly over time within a week,which was markedly lower than those in the D0,D1,and D2 group(P<0.05).The positive expression rates of RAGE and p-NF-kB protein in the D3 group was substantially higher than the rates of the D1 and D2 group(P<0.05),and there was no great difference in the positive expression rates of RAGE and p-NF-kB protein in the D1 and D2 group(P>0.05).The positive unit(PU)value of the FGF-2 protein in the D3 group was higher than the value of the D0,D1 and D2 group(P<0.05),and the PU value of FGF-2 protein in D1 had no statistical meaningfulness in contrast to those in D2 group(P>0.05).Conclusion The endocrine factor FGF-2 involved in the generation and maintenance of DNP in rats.The PWMT and PWTL of diabetic rats could be reduced by pyridoxamine and simvastatin through inhibiting the activation of RAGE and p-NF-kB and the expression of FGF-2 protein.Besides,the pyridoxamine and simvastatin had similar improvement effects.

关 键 词：吡哆胺 辛伐他汀 免疫荧光染色 神经病理性疼痛 纤维细胞生长因子2 p-NF-κB蛋白 

分 类 号：R587.2[医药卫生—内分泌]