龙胆苦苷对糖尿病周围神经痛的治疗作用及对AMPK信号通路的影响  

Therapeutic effect of gentiopicrin on peripheral diabetic neuralgia and influence of AMPK signaling pathway

作　　者：鲁义 姚嘉茵[2] 王保 陈陈燕 劳俊铭 刘栋 尧新华 LU Yi;YAO Jiayin;WANG Bao;CHEN Chenyan;LAO Junming;LIU Dong;YAO Xinhua(Department of Anesthesiology,Affiliated TCM Hospital of Guangzhou Medical University,Guangzhou 510130;Department of Gastroenterology,Sixth Affiliated Hospital of Sun Yat-Sen University,Guangzhou 510655,China)

机构地区：[1]广州医科大学附属中医医院麻醉科,广州510130 [2]中山大学附属第六医院消化科,广州510655

出　　处：《临床与病理杂志》2020年第12期3095-3101,共7页Journal of Clinical and Pathological Research

基　　金：广东省中医药局科研项目(20191247和20201257);广州市卫生和计划生育科技项目(20192A011008)。

摘　　要：目的:进一步明确龙胆苦苷对AMPK–/–大鼠的治疗作用以及对PPAR-γ/AMPK/ACC信号通路表达的影响,以评估AMPK在DPN致病及药物干预中的作用。方法:采用AMPK–/–大鼠,通过链脲佐菌素(STZ)诱导DPN大鼠模型。随机分组,每组大鼠10只:1)空白对照组;2)模型组;3)基因缺陷模型组(在AMPK–/–大鼠上采用STZ诱导DPN模型);4)龙胆苦苷治疗组(DPN+龙胆苦苷20 mg/kg);5)基因缺陷治疗组(DPN+龙胆苦苷20 mg/kg+AMPK–/–)。记录实验开始时(D0)及结束时(D14)的体重,同时检测血糖值;检测各组大鼠运动神经传导速度(motor nerve conduction velocity,MNCV)及感觉神经传导速度(sensory nerve conduction velocity,SNCV)的检测;采用RT-PCR法检测PPAR-γ/AMPK/ACC信号通路各因子的基因表达水平。结果:龙胆苦苷治疗后可以提高大鼠的体重,减低血糖值(P<0.05),但是在AMPK–/–的大鼠模型上,龙胆苦苷的治疗作用被明显减弱(P<0.05)。模型组大鼠存在MNCV及SNCV的下降,而且PPAR-γ/AMPK/ACC信号通路表达异常。龙胆苦苷药物干预后显著提高MNCV及SNCV,促进PPAR-γ和AMPK表达,抑制ACC表达(P<0.05)。但是,与普通大鼠的治疗组比较,龙胆苦苷在AMPK–/–的DPN动物模型中未能有效改善MNCV及SNCV;未能有效促进AMPK表达及抑制下游ACC表达(P<0.05)。结论:PPAR-γ/AMPK/ACC信号通路中PPAR-γ通过下游关键因子AMPK的作用,影响下游ACC表达。AMPK是龙胆苦苷发挥治疗作用的重要因素。Objective:To further clarify the therapeutic effect of gentiopicrin on AMPK–/–DPN rat models as well as its modification in the expressions of PPAR-γ/AMPK/ACC signaling pathway.Further to evaluate the role of AMPK in DPN pathogenesis and drug intervention.Methods:DPN rat models were induced by streptozotocin(STZ)using AMPK–/–rats.All the rats were randomly divided into 5 groups with 10 rats each:1)control group;2)DPN group;3)AMPK–/–DPN group(STZ-induced DPN model on AMPK–/–rats);4)gentiopicrin group(DPN+Gent 20 mg/kg);5)AMPK–/–intervention group(DPN+Gent 20 mg/kg+AMPK–/–).Weight and blood sugar at the beginning(D0)and the end of experiment(D14)were recorded and measured.Motor nerve conduction velocity(MNCV)and sensory nerve conduction velocity(SNCV)were detected while gene expressions of PPAR-γ/AMPK/ACC signaling pathway were evaluated.Results:After intervention with gentiopicrin,the average body weight increased and blood glucose decreased,the effect of gentiopicrin was weaken in AMPK–/–rat models.There was a significant decrease of MNCV and SNCV in DPN group with abnormal expression of PPAR-γ/AMPK/ACC signaling pathway.Intervened by gentiopicrin,MNCV and SNCV increased,PPAR-γand AMPK expressions were enhanced,and ACC expression was inhibited(P<0.05).Nevertheless,compared with the general DPN rats with Gent intervention,gentiopicrin administrated in AMPK–/–DPN rats failed to improve the MNCV and SNCV,neither to promote AMPK expression nor inhibit the ACC expression(P<0.05).Conclusion:PPAR-γaffected ACC expression by means of downstream key factor AMPK in PPAR-γ/AMPK/ACC signaling pathway.AMPK acted as an extremely important factor for gentiopicrin exerting therapeutic effect in DPN.

关 键 词：龙胆苦苷 糖尿病周围神经痛 AMPK 神经传导速度 

分 类 号：R285.5[医药卫生—中药学]