温润通络法对糖尿病模型大鼠的神经保护作用

Neuroprotective Effect of Wenrun Tongluo Method on Diabetic Rats

目的:研究温润通络方对糖尿病(DM)模型大鼠坐骨神经电生理及坐骨神经组织中血管内皮生长因子(VEGF)、碱性成纤维生长因子(bFGF)的影响,探讨温润通络法对糖尿病周围神经病变(DPN)的神经保护作用及其部分作用机理。方法:实验动物随机分为空白组、模型组、温润通络方高、低剂量组、血府逐瘀汤组。采用链脲佐菌素(STZ)腹腔注射的方法建立大鼠DM模型,观察大鼠一般状态和坐骨神经形态功能变化,采用荧光分光光度法、比色法和化学法测定醛糖还原酶(AR)活性、Na^+-K^+-ATP酶和山梨醇(SNS)的表达情况。免疫组化法检测坐骨神经及其周围组织VEGF、bFGF表达。结果:与空白组相比,模型组坐骨神经病变表现为神经纤维肿胀,鞘细胞减少,神经外膜毛细血管扩张充血,炎细胞浸润;模型组大鼠坐骨神经AR活性和SNS含量显著升高(P<0.01),Na^+-K^+-ATP酶活性显著降低(P<0.01);坐骨神经及其周围组织中VEGF、bFGF表达显著升高(P<0.01);经药物治疗后,与模型组比较,温润通络方高剂量组大鼠坐骨神经AR活性和SNS含量显著降低(P<0.01),Na^+-K^+-ATP酶活性升高(P<0.01),各药物组坐骨神经组织VEGF、bFGF表达均降低(P<0.01),各中药干预组中,温润通络方高剂量组降低最为显著。结论:温润通络方不仅降低DM大鼠坐骨神经AR和SNS含量、提高Na^+-K^+-ATP酶活性,还可促进坐骨神经及其周围组织中的VEGF、bFGF表达,说明温润通络法可通过加强对周围神经功能的保护作用而达到改善坐骨神经病变,治疗DPN的作用。

Objective:to study the effects of Wenrun Tongluo Recipe on the electrophysiology of sciatic nerve and the levels of vascular endothelial growth factor(VEGF)and basic fibroblast growth factor(bFGF)in sciatic nerve tissue of diabetic model(DM)rats,and to explore the neuroprotective effect of Wenrun Tongluo Recipe on diabetic peripheral neuropathy(DPN)and some mechanism.Methods:The experimental animals were randomly divided into blank group,model group,high and low dose Wenrun Tongluo group,and Xuefu Zhuyu Decoction group.DM rats were established by intraperitoneal injection of streptozotocin(STZ).The general state and the morphological and functional changes of sciatic nerve were observed.The activity of aldose reductase(AR),the expression of Na^+-K^+-ATPase and sorbitol(SNS)were measured by fluorescence spectrophotometry,colorimetry and chemical methods.The expressions of VEGF and bFGF were detected by immunohistochemistry.Results:Compared with the blank group,the sciatic neuropathy in the model group showed swelling of nerve fibers,decrease of sheath cells,dilation and congestion of nerve adventitia capillaries and infiltration of inflammatory cells;AR activity and SNS content of sciatic nerve in model group were significantly increased(P<0.01),Na^+-K^+-ATPase activity was significantly decreased(P<0.01);VEGF and bFGF expression in sciatic nerve and its surrounding tissues were significantly increased(P<0.01);Compared with the model group,the AR activity and SNS content of the high-dose Wenrun Tongluo group were significantly decreased(P<0.01),Na^+-K^+-ATPase activity was increased(P<0.01),and the expression of VEGF and bFGF in the sciatic nerve tissue of each medicianl group were decreased(P<0.01);among the intervention groups,the high-dose Wenrun Tongluo group decreased the most significantly.Conclusion:Wenrun Tongluo Recipe can not only reduce the content of AR and SNS in the sciatic nerve of DM rats,increase the activity of Na^+-K^+-ATPase,but also promote the expressions of VEGF and bFGF in the sciatic nerve and its surrounding tissues,which indicates that Wenrun Tongluo Recipe can improve the sciatic neuropathy and treat DPN by strengthening the protection of peripheral nerve function.