苯扎贝特治疗脂蛋白脂肪酶缺陷症1例及机制探讨

doi:10.3760/cma.j.cn441417-20250515-22021

国际医药卫生导报 ›› 2025, Vol. 31 ›› Issue (22): 3804-3808.DOI: 10.3760/cma.j.cn441417-20250515-22021

苯扎贝特治疗脂蛋白脂肪酶缺陷症1例及机制探讨

王振竞¹ 田明忠² 刘欣¹ 李鑫¹ 徐潮³ 王淑萍¹

¹东营市人民医院（山东省立集团东营医院）内分泌科东营市内分泌代谢病分子诊断重点实验室，东营 257091；²东营市人民医院（山东省立集团东营医院）优生遗传科东营市医学遗传学与生殖健康重点实验室，东营 257091；³山东第一医科大学附属省立医院内分泌科，济南 250021

收稿日期:2025-05-15 出版日期:2025-11-01 发布日期:2025-11-19
通讯作者: 徐潮，Email：doctorxuchao@163.com；王淑萍，Email：renzhendoctor@163.com
基金资助:
国家重点研发计划（2023YFC2506006）；东营市自然科学基金（No.2023ZR018）

Bezafibrate for one patient with lipoprotein lipase deficiency and its molecular mechanism

Wang Zhenjing¹, Tian Mingzhong², Liu Xin¹, Li Xin¹, Xu Chao³, Wang Shuping¹

¹Department of Endocrinology, Dongying People's Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Laboratory of Molecular Diagnosis of Endocrine and Metabolic Diseases of Dongying City, Dongying 257091, China; ²Department of Eugenics and Genetics, Dongying People's Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying 257091, China; ³Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China

Received:2025-05-15 Online:2025-11-01 Published:2025-11-19
Contact: Xu Chao, Email: doctorxuchao@163.com; Wang Shuping, Email: renzhendoctor@163.com
Supported by:
National Key Research and Development Program (2023YFC2506006); Dongying City Natural Science Foundation (No.2023ZR018)

摘要/Abstract

摘要： 目的　探讨苯扎贝特治疗脂蛋白脂肪酶缺陷症（lipoprotein lipase deficiency，LPLD）的效果及潜在分子机制。方法　报道东营市人民医院收治的１例脂蛋白脂肪酶（lipoprotein lipase，LPL）基因复合杂合突变（c.3G>C及c.835_836delCT）所致LPLD患者，对其临床资料、治疗反应及随访数据进行分析。采用AutoDock Vina软件分别进行苯扎贝特与LPL-野生型及突变型的分子对接模拟，通过PyMol可视化分析结合构象。结果　苯扎贝特治疗后三酰甘油下降63.7%；分子对接模拟显示，苯扎贝特与LPL-突变型在多肽“盖子”结构域及附近结合，结合能为-5.305 kcal/mol，可能诱导构象变化部分恢复酶功能；同时作为泛过氧化物酶体增殖物激活受体（eroxisome proliferator-activated receptor，PPAR）激动剂，苯扎贝特通过激活PPARα、β、γ多通路协同降脂。结论　苯扎贝特对该例LPLD患者表现出显著疗效，其机制可能与其直接调控LPL突变酶活性及系统激活PPAR通路有关。

关键词: 脂蛋白脂肪酶缺陷症, 苯扎贝特, 分子对接, PPAR通路

Abstract:

Objective　To investigate the effect of bezafibrate in the treatment of lipoprotein lipase deficiency (LPLD) and its potential molecular mechanisms. Methods　A case of LPLD caused by compound heterozygous mutations (c.3G>C and c.835_836delCT) in the lipoprotein lipase (LPL) gene was reported. The clinical data, treatment response, and follow-up data were analyzed. Molecular docking simulations of bezafibrate with both the wild-type and mutant LPL were performed using the AutoDock Vina software, and binding conformations were visualized using PyMol. Results　After the treatment with bezafibrate, the triglyceride level in the patient decreased by 63.7%. The molecular docking showed that bezafibrate binded to the polypeptide "lid" domain and adjacent regions of the mutant LPL, with a binding energy of -5.305 kcal/mol, potentially inducing conformational changes that partially restore enzyme function. Additionally, as a pan-PPAR agonist, bezafibrate synergistically lowered the lipids activating the PPARα, β, and γ pathways. Conclusions　Bezafibrate demonstrates significant efficacy for patients with LPLD. Its mechanism may be related to direct modulation of mutant LPL activity and systemic activation of PPAR pathways.

Key words:

Lipoprotein lipase deficiency, Bezafibrate, Molecular docking, PPAR pathways

王振竞田明忠刘欣李鑫徐潮王淑萍. 苯扎贝特治疗脂蛋白脂肪酶缺陷症1例及机制探讨[J]. 国际医药卫生导报, 2025, 31(22): 3804-3808.

Wang Zhenjing, Tian Mingzhong, Liu Xin, Li Xin, Xu Chao, Wang Shuping. Bezafibrate for one patient with lipoprotein lipase deficiency and its molecular mechanism[J]. International Medicine and Health Guidance News, 2025, 31(22): 3804-3808.

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苯扎贝特治疗脂蛋白脂肪酶缺陷症1例及机制探讨

Bezafibrate for one patient with lipoprotein lipase deficiency and its molecular mechanism

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