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基于细胞自噬探讨肝豆灵片对Wilson病的干预研究

Study on the Intervention of Gandouling Tablets in Wilson Disease Based on Autophagy
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摘要 目的探讨肝豆灵片对Wilson病(Wilson disease,WD)患者的临床疗效及自噬在其中的作用。方法前瞻性收集2021年2月~2022年10月安徽中医药大学第一附属医院神经内科收治的WD患者77例,将其分为治疗组(n=42)和对照组(n=35),其中治疗组予以肝豆灵片(gandouling tablets,GDLT)联合西药治疗,对照组予以西药治疗。选取患者健康同胞40例作为健康组。所有研究对象均采用酶联免疫吸附试验检测血清Beclin-1、p62、LC3-Ⅱ水平的变化,提取外周血单个核细胞并进行实时荧光定量聚合酶链反应(real-time quantitative polymerase chain reaction,RT-qPCR)检测其基因表达水平;所有WD患者进行统一肝豆状核变性分级量表(unified Wilson disease rating scale,UWDRS)评分。分析UWDRS评分变化与自噬蛋白Beclin-1、LC3-Ⅱ、p62水平的相关性;分析GDLT对UWDRS评分及自噬蛋白Beclin-1、p62、LC3-Ⅱ的影响。结果WD患者Beclin-1、LC3-Ⅱ蛋白及mRNA表达水平上升,p62显著下降。UWDRS评分与Beclin-1、LC3-Ⅱ呈正相关,与p62呈负相关。GDLT干预治疗后,UWDRS评分改善显著,Beclin-1、LC3-Ⅱ水平下降显著,p62上升明显(P<0.05)。结论Beclin-1、p62、LC3-Ⅱ与WD病情发展密切相关,对评估WD病情及预后具有重要意义。GDLT干预治疗可抑制WD自噬的过度激活,逆转WD病情进展。 Objective To investigate the clinical efficacy of gandouling tablets in patients with Wilson disease(WD)and the role of autophagy in it.Methods A total of 77WD patients admitted to the Department of Neurology of the First Affiliated Hospital of Anhui U-niversity of Chinese Medicine from February 2021 to October 2022 were retrospectively collected,and divided into treatment group(n=42)and control group(n=35).The treatment group was treated with gandouling tablets(GDLT)combined with western medicine,the control group was treated with western medicine.A total of 4Ohealthy siblings of the patients were selected as the healthy group.The ser-um Beclin-1,p62 and LC3-I levels of all subjects were detected by enzyme-linked immunosorbent assay(ELISA),and gene ex-pression levels were detected by extracting peripheral blood single nucleated cells and real-time quantitative polymerase chain reaction(RT-qPCR).All WD patients were scored on the unified Wilson disease rating scale(UWDRS).The correlation between the changes of UWDRS score and the levels of Beclinl,LC3-II and p62 in WD patients was also analyzed.The effects of GDLT treatment on UW-DRS score and autophagy proteins Beclin-I,p62 and LC3-II in WD patients were analyzed.Results The expression levels of Beclin-1,LC3-II protein and mRNA were increased and p62 was significantly decreased in WD patients.UWDRS scores were posi-tively correlated with Beclin-1 and LC3-II,and negatively correlated with p62.After GDLT intervention,UWDRS score improved sig-nificantly,Beclin-1 and LC3-I levels decreased significantly,and p62 increased significantly(P<0.05).Conclusion Beclin-1,p62,LC3-II are closely related to the development of WD,which is of great significance for the evaluation and prognosis of WD.CDLT intervention can inhabit the overactivation of WD autophagy and reverse the progression of WD.
作者 钱建华 徐国存 曾靖喻 蒋媛媛 张玲 陈怀珍 王萍 张静 QIAN Jianhua;XU Guocun;ZENG Jingyu(Anhui University of Chinese Medicine,Anhui 230012,China)
出处 《医学研究杂志》 2024年第7期57-61,共5页 Journal of Medical Research
基金 国家自然科学基金青年科学基金资助项目(82104783) 安徽省卫生健康委员会“江淮名医培育工程”项目(ahsjhmypygc20230076)。
关键词 WILSON病 细胞自噬 肝豆灵片 UWDRS评分 Wilson disease Autophagy Gandouling tablets UWDRS
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