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二氢杨梅素经激活AMPK/ULK1通路改善2型糖尿病大鼠帕金森病样病变

李琪¹, 陈碾², 罗金定¹, 伍惠霖³, 王紫涵¹, 李梦伟¹, 奉水东⁴, 凌宏艳^1,*

¹南华大学衡阳医学院生理学教研室，衡阳 421001；² 南华大学附属第一医院医疗美容科，衡阳 421001；³南华大学衡阳医学院2018级临床10班，衡阳 421001；⁴南华大学公共卫生学院社会医学与卫生事业管理学教研室，衡阳 421001

摘要

本文旨在探究二氢杨梅素(dihydromyricetin, DHM)对2型糖尿病(type 2 diabetes mellitus, T2DM)大鼠帕金森病(Parkinson’s disease, PD)样病变的作用及机制。喂养Sprague Dawley (SD)大鼠高脂饲料和腹腔注射链脲佐菌素(streptozocin, STZ)建立T2DM模型，用DHM (每天125或250 mg/kg灌胃)处理24周，用平衡木实验检测大鼠运动能力，用免疫组织化学法检测大鼠中脑多巴胺能(dopaminergic, DA)神经元细胞变化和自噬启动相关蛋白ULK1的表达，用Western blot检测大鼠中脑α-突触核蛋白(α-synuclein, α-syn)、酪氨酸羟化酶(tyrosine hydroxylase, TH)蛋白表达和AMPK活化水平。结果显示，与正常对照组相比，长期患T2DM的大鼠出现运动功能障碍，中脑α-syn聚集增加，TH蛋白表达水平下调，DA能神经元数目减少，AMPK活化水平降低，ULK1表达水平显著下调，24周DHM (每天250 mg/kg)处理明显改善T2DM大鼠上述PD样病变，提高AMPK活性，上调ULK1蛋白表达。上述结果提示，DHM可能通过激活AMPK/ULK1通路改善T2DM大鼠PD样病变。

关键词： 二氢杨梅素; 2型糖尿病大鼠; 帕金森病样病变; AMPK/ULK1通路

Dihydromyricetin improves Parkinson’s disease-like lesions in T2DM rats by activating AMPK/ULK1 pathway

LI Qi¹, CHEN Nian², LUO Jin-Ding¹, WU Hui-Lin³, WANG Zi-Han¹, LI Meng-Wei¹, FENG Shui-Dong⁴, LING Hong-Yan^1,*

¹Department of Physiology, Hengyang Medical College, University of South China, Hengyang 421001, China；²Department of Medical Cosmetology, the First Affiliated Hospital, University of South China, Hengyang 421001, China；³Clinical Medicine Class 10, Grade 2018, Hengyang Medical College, University of South China, Hengyang 421001, China；⁴Department of Social Medicine and Health Management, School of Public Health, University of South China, Hengyang 421001, China

Abstract

The purpose of this study was to explore the effect and mechanism of dihydromyricetin (DHM) on Parkinson’s disease (PD)-like lesions in type 2 diabetes mellitus (T2DM) rats. The T2DM model was established by feeding Sprague Dawley (SD) rats with high-fat diet and intraperitoneal injection of streptozocin (STZ). The rats were intragastrically administered with DHM (125 or 250 mg/kg per day) for 24 weeks. The motor ability of the rats was measured by balance beam experiment, the changes of dopaminergic (DA) neurons and the expression of autophagy initiation related protein ULK1 in the midbrains of the rats were detected by immunohistochemistry, and the protein expression levels of α-synuclein (α-syn), tyrosine hydroxylase (TH), as well as AMPK activation level, in the midbrains of the rats were detected by Western blot. The results showed that, compared with normal control, the rats with long-term T2DM exhibited motor dysfunction, increased α-syn aggregation, down-regulated TH protein expression, decreased number of DA neurons, declined activation level of AMPK, and significantly down-regulated ULK1 expression in the midbrain. DHM (250 mg/kg per day) treatment for 24 weeks significantly improved the above PD-like lesions, increased AMPK activity, and up-regulated ULK1 protein expression in T2DM rats. These results suggest that DHM may improve PD-like lesions in T2DM rats by activating AMPK/ULK1 pathway.

Key words: dihydromyricetin; type 2 diabetic rats; Parkinson’s disease-like lesions; AMPK/ULK1 signaling

收稿日期：　　录用日期：

通讯作者：凌宏艳　　E-mail:

DOI: 10.13294/j.aps.2023.0009

引用本文：

李琪, 陈碾, 罗金定, 伍惠霖, 王紫涵, 李梦伟, 奉水东, 凌宏艳. 二氢杨梅素经激活AMPK/ULK1通路改善2型糖尿病大鼠帕金森病样病变[J]. 生理学报 2023; 75 (1): 59-68.

LI Qi, CHEN Nian, LUO Jin-Ding, WU Hui-Lin, WANG Zi-Han, LI Meng-Wei, FENG Shui-Dong, LING Hong-Yan. Dihydromyricetin improves Parkinson’s disease-like lesions in T2DM rats by activating AMPK/ULK1 pathway. Acta Physiol Sin 2023; 75 (1): 59-68 (in Chinese with English abstract).