文章摘要

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

作者: 1鲁义, 2姚嘉茵, 1王保, 1陈陈燕, 1劳俊铭, 1刘栋, 1尧新华
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
通讯: 尧新华 Email: yxh200210@126.com
DOI: 10.3978/j.issn.2095-6959.2020.12.002
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。
关键词: 龙胆苦苷;糖尿病周围神经痛;AMPK;神经传导速度

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

Authors: 1LU Yi, 2YAO Jiayin, 1WANG Bao, 1CHEN Chenyan, 1LAO Junming, 1LIU Dong, 1YAO Xinhua
1 Department of Anesthesiology, Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou 510130, China
2 Department of Gastroenterology, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, China

CorrespondingAuthor: YAO Xinhua Email: yxh200210@126.com

Foundation: This work was supported by the Scientific Research Project of Guangdong Traditional Chinese Medicine (20191247 and 20201257) and Guangzhou Health and Family Planning Science and Technology Project (20192A011008), China.

Abstract

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-γ and 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-γ affected 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.
Keywords: gentiopicrin; diabetic peripheral neuralgia; AMPK; nerve conduction velocity