小檗碱改善糖尿病大鼠神经病变急性疼痛的作用机制研究  

Effect and mechanism of berberine on the improvement of acute pain in diabetic neuropathy rats

作　　者：裴翔 欧阳茹 陈铅琴 刘丹 PEI Xiang;OUYANG Ru;CHEN Qian-qin;LIU Dan(Department of Endocrine,Third People’s Hospital of Hainan Province,Sanya 572000,Hainan Province,China)

机构地区：[1]海南省第三人民医院内分泌科,海南三亚572000

出　　处：《中国临床药理学杂志》2020年第17期2672-2674,2685,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的观察小檗碱对链脲作菌素(STZ)-诱导的糖尿病神经病变急性疼痛的改善作用及其机制。方法大鼠单次腹腔内注射STZ 55 mg·kg^-1建立糖尿病大鼠模型。按照体重将造模成功大鼠随机分为4组:模型组、胰岛素组(2 u·kg^-1)和低、高2个剂量(灌胃给予小檗碱20,60 mg·kg^-1)实验组,每组7只;另取正常大鼠7只作为正常组。均连续给予2周。用酶联免疫吸附法测血清中肿瘤坏死因子-α(TNF-α)含量,用蛋白质印迹法检测脊髓和背根节(DRG)中蛋白激酶Cε(PKCε)和瞬时受体电位香草酸亚型1(TRPV1)蛋白表达水平(灰度值)。结果正常组、模型组、胰岛素组和低、高2个剂量实验组的TNF-α含量分别为(51.24±7.83),(138.44±9.36),(54.54±5.16),(105.12±4.26)和(71.32±9.14)pg·mL^-1;这5组的脊髓PKCε表达水平分别为0.32±0.05,1.55±0.22,0.67±0.08,0.89±0.18和0.68±0.09。这5组的脊髓的TRPV1表达水平分别为0.23±0.04,1.78±0.25,0.80±0.10,1.18±0.16和0.86±0.08。上述指标:模型组与正常组比较,差异均有统计学意义(均P<0.01);胰岛素组和低、高2个剂量实验组与模型组相比,差异均有统计学意义(P<0.01,P<0.05)。结论小檗碱通过抑制炎症过程和阻断PKC通路来抑制TRPV1激活,从而发挥其改善糖尿病神经病变急性疼痛的作用。Objective To study the improvement effect of berberine on streptozocin(STZ)-induced diabetic neuropathy acute pain and its possible mechanism Methods Rats were injected with STZ 55 mg·kg^-1 to establish diabetes model.Successful rat model were randomly divided into 4 groups according to weight:model group,low-dose,high-dose experimental groups(20,60 mg·kg^-1 berberine)and insulin group(2 u·kg^-1 insulin),with 7 rats in each group,for 2 weeks;another 7 normal rats were selected as the normal group.Tumor necrosis factor-α(TNF-α)in serum was measured by ELISA.Protein expression levels of protein kinase Cε(PKCε)and transient receptor potential vanilloid subtype 1(TRPV1)in spinal cord and dorsal root ganglion(DRG)were analyzed by Western blot.Results The TNF-αcontents in normal group,model group,insulin group,and low-dose,high-dose experimental groups were(51.24±7.83),(138.44±9.36)(54.54±5.16),(105.12±4.26)and(71.32±9.14)pg·mL^-1;the expression level of PKCεin the 5 groups were0.32±0.05,1.55±0.22,0.67±0.08,0.89±0.18 and 0.68±0.09;the expression level of TRPV1 in the 5 groups were 0.23±0.04,1.78±0.25,0.80±0.10,1.18±0.16 and 0.86±0.08.Comparison between model group and normal group,the difference of the factors were significant(all P<0.01);comparison between insulin group,low-dose,high-dose experimental groups and model group,the difference of the factors were significant(P<0.05,P<0.01).Conclusion Berberine could inhibit the inflammatory process and TRPV1 activation by blocking the PKC pathway,thereby playing its role in improving the acute pain of diabetic neuropathy.

关 键 词：糖尿病周围神经病变 小檗碱 肿瘤坏死因子-α 蛋白激酶CΕ 瞬时受体电位香草酸亚型1 

分 类 号：R97[医药卫生—药品]