GLP-1类似物利拉鲁肽对糖尿病神经病变大鼠坐骨神经PARP-1/NF-κB表达的影响  

The effect of GLP-1 analogue liraglutide on the expression of PARP-1/NF-κB in the sciatic nerve of diabetic neuropathy rats

作　　者：曹晓红[1] 徐勇 陈平[1] Cao Xiao hong;Xu Yong;Chen Ping(Department of Geriatric Endocrinology,Sichuan Provincial People's Hospital;Department of Endocrinology and Metabolism,Southwest Medical University)

机构地区：[1]四川省人民医院老年内分泌科,成都610072 [2]西南医科大学附属医院内分泌代谢科,成都646000

出　　处：《重庆医科大学学报》2021年第12期1425-1433,共9页Journal of Chongqing Medical University

基　　金：四川省科技计划资助项目(编号:2014SZ0020)。

摘　　要：目的:通过构建大鼠糖尿病周围神经病变(diabetic peripheral neuropathy,DPN)模型探究胰高血糖素样肽1(glucagonlike peptide 1,GLP-1)类似物利拉鲁肽对DPN大鼠坐骨神经聚腺苷二磷酸核糖聚合酶/激活核因子-κB(poly ADP-ribose polymerase/nuclear factor kappa-B,PARP/NF-κB)表达的影响。方法:SD大鼠84只,随机选12只作为正常组;其余大鼠均采用链脲佐菌素诱导建立DPN模型。建模成功后,抽取72只大鼠随机分为模型组,胰岛素组,甲钴胺组,利拉鲁肽低、中、高剂量组。正常组和模型组皮下注射等体积生理盐水,胰岛素组给予胰岛素治疗,甲钴胺组给予甲钴胺治疗,给药组给予不同剂量利拉鲁肽治疗,共治疗8周。记录各组大鼠体质量和血糖,测定神经反应速度,ELISA检测炎症因子,流式细胞术检测细胞凋亡,Western blot检测PARP-1、NF-κB蛋白表达,EMSA检测NF-κB转录活性。选择RSC96细胞建立高糖环境下细胞损伤模型,应用基因芯片预测PARP-靶基因,并通过转染PARP-1进行检验。结果:与模型组比较,利拉鲁肽治疗后大鼠体质量显著增加,血糖显著降低,神经反应速度提高(P<0.05);大鼠实验和细胞实验显示利拉鲁肽给药后细胞炎症因子含量及PARP和NF-κB蛋白表达较模型组显著降低,高剂量组降低幅度更明显(P<0.05);大鼠神经细胞凋亡率较模型组显著降低(P<0.05);利拉鲁肽抑制了NF-κB的转录活性;PARP-1转染组炎症因子和PARP-1、NF-κB蛋白水平显著高于中剂量组(P<0.05),PARP-1/NF-κB是GLP-1对糖尿病神经病变大鼠抗炎症作用的重要靶点。结论:利拉鲁肽可以降低DPN大鼠坐骨神经PARP-1和NF-κB的表达水平,从而降低大鼠坐骨神经损伤,起到防治糖尿病周围神经病变损伤的作用。Objective:To investigate the effect of glucagon-like peptide 1(GLP-1) analog liraglutide on the expression of PARP and NF-κB in diabetic peripheral neuropathy(DPN) rats by establishing a rat model of DPN. Methods:A total of 84 SD rats were randomly selected as control group,and the other rats were induced by streptozotocin to establish DPN model. After successful modeling,72 rats were randomly divided into model group,insulin group,mecobalamin group,and liraglutide low,medium and high dose groups. Normal group and model group were subcutaneously injected with equal volume of normal saline. Insulin group was treated with insulin,mecobalamin group was treated with mecobalamin,and drug groups were treated with different doses of liraglutide for 8 weeks. The body weight and blood glucose of rats in each group were recorded,nerve reaction speed was measured,inflammatory factors were detected by ELISA,apoptosis was detected by flow cytometry,and PARP-1 and NF-κB protein expression were detected by Western blot. RSC96 cells were selected to establish cell damage model in high glucose environment. PARP target gene was predicted by gene chip and tested by transfection of PARP-1. Results:Compared with the model group,liraglutide significantly increased the body weight,significantly decreased blood glucose,and increased the speed of nerve reaction(P<0.05);rat and cell experiments showed that the content of inflammatory factors and the expression of PARP and NF-κB protein were significantly decreased after liraglutide treatment,and the reduction was more obvious in the high-dose group(P<0.05);the apoptosis rate of nerve cells in rats was significantly decreased than that in the model group(P<0.05). Liraglutide inhibited the transcriptional activity of NF-κB. The levels of inflammatory factors,PARP-1 and NF-κB protein in PARP-1 transfection group were significantly higher than those in middle dose group(P<0.05). PARP-1/NF-κB is an important target of GLP-1 in anti-inflammatory effect of diabetic neuropathy rats. Conclus

关 键 词：利拉鲁肽 糖尿病周围神经病变 坐骨神经损伤 聚腺苷二磷酸核糖聚合酶-1 核因子-κB 

分 类 号：R58[医药卫生—内分泌]