复方龙芪汤对2型糖尿病大鼠周围神经病变的作用和机制

Effect of Compound Long-Qi Decoction on Peripheral Neuropathy in Type 2 Diabetic Rats

目的:研究复方龙芪汤对高脂高糖饲料喂养联合腹腔注射链脲佐菌素(STZ)诱发的2型糖尿病大鼠周围神经病变的作用,并探讨其可能的作用机制。方法:100只Wistar大鼠,随机选取10只作为正常对照组,其余大鼠采用高脂高糖饲料喂养联合腹腔注射小剂量STZ建立2型糖尿病模型大鼠,造模4周后,模型组大鼠按血糖水平平行分为5组,分别为模型对照组,木丹颗粒组(1.75 g/kg),复方龙芪汤高、中、低剂量(6.33、3.17、1.58 g/kg)组。灌胃给药5周后,测定大鼠热、冷刺激反应时间,大鼠强迫跑步被电击次数和坐骨神经传导速度;灌胃给药9周后,测定坐骨神经传导速度、坐骨神经和红细胞的山梨醇含量,空腹血糖血脂、糖化血红蛋白含量及SOD、T-AOC活性和MDA含量。采用ELISA测定大鼠血清AR和实时PCR检测AR mRNA的表达。结果:与正常对照组比较,高脂高糖饲料喂养联合腹腔注射STZ建立的2型糖尿病模型大鼠坐骨神经传导速度降低(P<0.05),坐骨神经以及红细胞山梨醇的含量增加(P<0.01,P<0.05),红细胞AR mRNA表达水平和血清AR显著升高(P<0.05),糖化血红蛋白显著升高(P<0.05)。复方龙芪汤能明显提高2型糖尿病大鼠坐骨神经传导速度(P<0.05),通过下调红细胞AR mRNA表达水平和血清AR,降低坐骨神经(P<0.01)和红细胞(P<0.05)中山梨醇的含量,但对空腹血糖血脂和糖化血红蛋白则没有显著性影响。结论:复方龙芪汤可以改善2型糖尿病大鼠的周围神经病变程度,其机制可能与其通过降低AR而减少红细胞和坐骨神经中的山梨醇的含量及降低机体氧化应激水平有关。

Objective:To investigate the effect of Compound Long-Qi Decoction on peripheral neuropathy in diabetic rats induced by streptozotocin(STZ) combined with high glucose and fat dietand explore its possible mechanism.Methods:A total 100 Wistar rats were included in the study, among them, 10 rats were randomly selected as control group, while the other rats were given the high glucose and fat diet and intraperitonealinjection of low-dose STZ to establish the rat model of diabetes. After 4 weeks modeling, according to the blood glucose,the model rats were divided into model group, Mudan Granules group(1.75 g/kg), Long-Qi Decoction groups(6.33,3.17,1.58 g/kg). After 5 weeks intragastricaladministration, the conduction velocity of sciatic nerve in ratswas determined by multichannel physiological signal acquisition and processing system, reaction time of cold and heat stimulation and number of electronic shocks in running training were determined. After 9 weeksintragastricaladministration,thesciatic nerve sorbitol content and erythrocyte sorbitol contentwas determined by HPLC, fasten blood glucose and lipids, glycosylated hemoglobin content and SOD,T-AOC and MDA were determined. The content of AR was determined by ELISA and AR mRNA expression determined by real time PCR. Results:Compared with the normal group, the conduction velocity of sciatic nerve was delayed in the model group(P<0.05),the sorbitol content of the sciatic nerve and erythrocyte increased(P<0.01, P<0.05), the level of AR mRNA expressionand content of AR increased(P<0.05), glycosylated hemoglobin content increased(P<0.05). The decoction could improve the sciatic nerve conduction velocity(P<0.05)and decrease thesorbitol content of the sciatic nerve(P<0.01)and theerythrocyte(P<0.05)in type 2 diabetic rats through down-regulation of the level of AR mRNA expression and content of AR. But there was no significant difference of fasten blood glucose and glycosylated hemoglobin. Conclusion:TheLong-Qi Decoction could promote the type 2 diabetic peripheral neuropathyand its mechanism may be related to inhibition of sorbitol pathway and reducing oxidative stress.