摘要
目的探讨二甲双胍对2型糖尿病并发神经病理性疼痛(DNP)大鼠的影响及其可能机制。方法将80只SD大鼠按随机数字表法分为正常对照组(n=15)和高脂高糖组(n=65), 分别给予正常饲料、高脂高糖饲料喂养, 于喂养前、喂养8周后称大鼠体质量、采用血糖仪检测大鼠空腹血糖, 采用ELISA法检测大鼠空腹胰岛素水平并计算胰岛素敏感指数(ISI)。喂养8周后测量高脂高糖组大鼠机械缩足反射痛阈值(MWT)和热缩足反射潜伏期(TWL)(基础值), 禁食12 h后腹腔注射链脲佐菌素(STZ)(35 mg/kg), 3 d后测量随机血糖, STZ注射后14 d再次称体质量并测量大鼠的MWT和TWL, 当MWT和TWL均≤基础值的85%时视为DNP造模成功(n=45), 否则归为糖尿病无痛组(n=15)。采用随机数字表法将造模成功大鼠分为DNP组、DNP+二甲双胍组、DNP+溶剂组, 每组15只。于STZ注射后14 d, DNP+二甲双胍组大鼠腹腔注射二甲双胍(200 mg/kg), 每天1次, 连续14 d。DNP组不做任何处理, DNP+溶剂组大鼠腹腔注射等量生理盐水。STZ注射后14 d及给药后3、7、14、21 d测量各组大鼠的MWT和TWL。给药后7、14、21 d ELISA法检测各组大鼠脊髓白细胞介素(IL)-6、IL-1β和肿瘤坏死因子-α(TNF-α)水平。给药后21 d免疫荧光染色检测各组大鼠脊髓离子钙接头蛋白-1(Iba-1)的表达;Western blotting检测各组大鼠脊髓Toll样受体4(TLR4)、核转录因子-κB(NF-κB)、磷酸化(p)-NF-κB、腺苷酸活化蛋白激酶(AMPK)、p-AMPK、过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)蛋白的表达。结果 (1)喂养8周后高脂高糖组大鼠的体质量高于正常对照组, STZ注射后14 d高脂高糖组大鼠的体质量低于正常对照组, 差异均有统计学意义(P<0.05)。STZ注射后3 d高脂高糖组大鼠的随机血糖高于正常对照组, 差异有统计学意义(P<0.05)。喂养8周后高脂高糖组大鼠的胰岛素水平高于正常对照组, ISI低于正常对照组, 差异�
Objective To investigate the role and mechanism of metformin in algesia of rats with type 2 diabetic neuropathic pain(DNP).Methods Eighty sprague-dawley rats were randomly divided into normal control group(n=15)and high-fat and high-glucose group(n=65);normal diet and high-fat and high-sugar diet were given,respectively;before and 8 weeks after feeding,the body mass of rats and fasting blood glucose level were recorded,fasting insulin level was detected by ELISA,and insulin sensitivity index(ISI)was calculated.Mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)8 weeks after feeding(baseline values)were measured in the high-fat and high-glucose group;after 12 h of fasting,intraperitoneal injection of streptozotocin(STZ,35 mg/kg)was performed;3 d after fasting,blood glucose was measured;14 d after STZ injection,body mass was recorded and MWT and TWL were measured again:when MWT and TWL were≤85%baseline values,it was defined that DNP model was successfully established(n=45);and the left were into the diabetic painless group(n=15).The rats with successful DNP were randomly divided into DNP group,DNP+vehicle group and DNP+metformin group(n=15);14 d after STZ injection,rats in the DNP+metformin group were given intraperitoneal injection of metformin(200 mg/kg)once daily for 14 consecutive d;DNP group did not accept any treatment,and rats in DNP+vehicle group were intraperitoneally injected with same amount of normal saline.MWT and TWL of all rats were measured 14 d after STZ injection,and 3,7,14 and 21 d after metformin injection.The expression levels of interleukin(IL)-6,IL-1β and tumor necrosis factor(TNF)-a were detected by ELISA 7,14 and 21 d after metformin injection.The fluorescence intensity of ionized calcium binding adaptor molecule-1(Iba-1)in the spinal cord was detected by immunofluorescence staining,and the expression levels of Toll-like receptor 4(TLR4),nuclear transcription factor(NF)-κB,phosphorylated(p)-NF-κB,adenylate activated protein kinase(AMPK),p-AMPK,and peroxisome prolife
作者
孙勇
刘武
张维
余菲
栾文康
赵晓雪
戴甫成
Sun Yong;Liu Wu;Zhang Wei;Yu Fei;Luan Wenkang;Zhao Xiaoxue;Dai Fucheng(Department of Pain Medicine,Affiliated People's Hospital of Jiangsu University,Zhenjiang 212000,China;department of Burn and Plastic Surgery,Affiliated People's Hospital of Jiangsu University,Zhenjiang 212000,China;Department of Ultrasound Medicine,Affiliated Hospital of Jiangsu University,Zhenjiang 212000,China)
出处
《中华神经医学杂志》
CAS
CSCD
北大核心
2021年第12期1194-1203,共10页
Chinese Journal of Neuromedicine
基金
国家自然科学基金青年项目(81802726)
镇江市第一人民医院科研项目(Y2020004)。
