基于AMPK/mTOR通路探究养血清脑颗粒对帕金森综合征大鼠的作用及机制  

The Effect and Mechanism of Yangxue Qingnao Granules (养血清脑颗粒) on Parkinson's Syndrome Rats Based on AMPK/mTOR Pathway

作　　者：李明[1] 李琦 罗佳晶 张佳诺 LI Ming;Li Qi;LUO Jiajing;ZHANG Jianuo(Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]北京中医药大学东直门医院,北京100700

出　　处：《中医药导报》2025年第1期27-31,60,共6页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金面上项目(82174340)。

摘　　要：目的:探究养血清脑颗粒(YXQNG)对帕金森综合征(PD)大鼠的作用及YXQNG在该过程中对AMPK/mTOR通路的调节机制。方法:将SPF级SD雄性大鼠随机分为对照组、模型组、YXQNG低剂量组、YXQNG高剂量组、YXQNG高+AMPK抑制剂(YXQNG高+Compound C)组,每组15只。评估各组大鼠的行为能力;苏木素-伊红(HE)染色观察大鼠黑质组织的病理学变化;免疫组化法检测大鼠黑质中酪氨酸羟化酶(TH)和α-突触核蛋白(α-Syn)的阳性表达;蛋白免疫印迹(Western blotting)检测大鼠纹状体中AMPK/mTOR通路及自噬相关蛋白的表达。结果:与对照组比较,模型组大鼠旋转圈数、脑黑质中MDA水平、α-Syn表达、多巴胺能神经元凋亡率、mTOR的磷酸化水平及p62的表达均升高,脑黑质中SOD水平、TH阳性表达、AMPK的磷酸化水平及LC3Ⅱ/Ⅰ的比例均降低(P<0.05);与模型组比较,YXQNG低、高剂量组大鼠的旋转圈数、脑黑质中MDA水平、α-Syn表达、多巴胺能神经元凋亡率、mTOR的磷酸化水平及p62的表达均降低,脑黑质中SOD水平、TH阳性表达、AMPK的磷酸化水平及LC3Ⅱ/Ⅰ的比例均升高(P<0.05);进一步加入AMPK抑制剂,结果发现高剂量YXQNG对PD大鼠的保护作用及对AMPK/mTOR通路的促进作用均被逆转(P<0.05)。结论:YXQNG可能通过促进AMPK/mTOR信号通路来保护PD大鼠。Objective:To investigate the impact of Yangxue Qingnao granule(YXQNG)on Parkinson's syndrome(PD)rats and its regulatory mechanism on the AMPK/mTOR pathway during this process.Methods:SPF grade SD male rats were randomly grouped into control group,model group,YXQNG low-dose group,YXQNG high-dose group,and YXQNG high+AMPK inhibitor(YXQNG high+Compound C)group,with 15 rats in each group.The behavioral ability of rats in each group was evaluated.Hematoxylin-eosin(HE)staining was applied to observe pathological changes in the substantia nigra of rats.Immunohistochemical method was applied to detect the positive expression of tyrosine hydroxylase(TH)andα-synaptic nuclear protein(α-Syn)in the substantia nigra of rats.Western blotting was applied to detect the expression of AMPK/mTOR pathway and autophagy related proteins in the rat striatum.Results:Compared with the control group,the number of rotations,the level of MDA,expression ofα-Syn,apoptosis rate of dopaminergic neurons,phosphorylation level of mTOR,and expression of p62 in the substantia nigra increased in the model group,while the levels of SOD,positive expression of TH,phosphorylation level of AMPK,and the proportion of LC3 II/I in the substantia nigra of the brain decreased(P<0.05).Compared with the model group,the number of rotations,the level of MDA,expression ofα-Syn,apoptosis rate of dopaminergic neurons,phosphorylation level of mTOR,and expression of p62 in the substantia nigra decreased in the YXQNG low and high dose groups while the levels of SOD,positive expression of TH, phosphorylation level of AMPK, and the proportion of LC3 Ⅱ/Ⅰ in the substantia nigra of the brain increased (P<0.05). Wirh addition of AMPK inhibitors, the protective effect of high-dose YXQNG on PD rats and its promoting effect on the AMPK/mTOR pathway were reversed (P<0.05). Conclusion: YXQNG may protect PD rats by promoting the AMPK/mTOR signaling pathway.

关 键 词：帕金森综合征 养血清脑颗粒 腺苷一磷酸激活蛋白激酶/哺乳动物雷帕霉素靶蛋白通路 自噬 大鼠 

分 类 号：R285.5[医药卫生—中药学]