对肝豆状核变性患者不同疾病阶段不同致病因素的研究。

Study on different pathogenic factors in different disease stages of patients with Wilson disease.

机构信息

Department of Neurology, The East Area of the First Affiliated Hospital, Sun Yat-Sen University, HuangPu East Street, 183#, Guangzhou, Guangdong, China.

Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, No. 58 Zhongshan Road 2, Guangzhou, 510080, China.

出版信息

Neurol Sci. 2021 Sep;42(9):3749-3756. doi: 10.1007/s10072-020-04973-7. Epub 2021 Jan 14.

DOI:10.1007/s10072-020-04973-7

PMID:33443665

Abstract

OBJECTIVE

To investigate in different stages of patients with Wilson disease (WD), there are different pathogenic factors such as metal deposition, oxidative stress, and inflammatory response in the brain.

METHODS

A total of 32 untreated WD patients and 10 normal controls were enrolled in the study. The neurological symptoms were evaluated using the modified Young scale. Liver function, metal metabolism, susceptibility-weighted imaging (SWI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) examination were done. The clinical disease stages were divided into metal deposition period, fiber damage period, and neuronal necrosis period according to the imaging results. The content of 24-h urine copper, serum copper, and serum iron; and the levels of catalase (CAT), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD), interleukin (IL-1), and tumor necrosis factor alpha (TNF-α) were detected.

RESULTS

The contents of urinary copper in WD patients at neuronal necrosis stage were lower than those in patients at the metal deposition stage (P = 0.011) and fiber injury stage (P = 0.023). The contents of NOS (P = 0.039) and NO (P = 0.047) in WD patients at the stage of fiber injury were higher than those of the normal control, while GSH-PX (P = 0.025) and CAT (P = 0.041) were lower in the neuronal necrosis stage. In the stage of neuronal necrosis, the levels of IL-1 (P = 0.030) and TNF-α were higher than those of the normal control (P = 0.042). The neurological symptom scores in patients with fiber injury (P = 0.013) and neuron injury were higher than those with metal deposition (P = 0.026).

CONCLUSION

There are different pathogenic factors in different stages of WD. At the neuronal necrosis stage, copper deposition was decreased in WD patients. In the stage of fiber injury and neuronal necrosis, there is oxidative stress injury in WD patients. In the neuronal necrosis phase, WD patients have an inflammatory response.

摘要

目的

探讨肝豆状核变性（WD）不同阶段患者脑内存在不同的致病因素，如金属沉积、氧化应激和炎症反应。

方法

共纳入 32 例未经治疗的 WD 患者和 10 例正常对照者。采用改良 Young 量表评估神经症状。进行肝功能、金属代谢、磁敏感加权成像（SWI）、弥散张量成像（DTI）和磁共振波谱（MRS）检查。根据影像学结果将临床疾病阶段分为金属沉积期、纤维损伤期和神经元坏死期。检测 24 小时尿铜、血清铜和血清铁含量，以及过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-PX）、丙二醛（MDA）、一氧化氮（NO）、一氧化氮合酶（NOS）、超氧化物歧化酶（SOD）、白细胞介素（IL-1）和肿瘤坏死因子α（TNF-α）水平。

结果

神经元坏死期 WD 患者尿铜含量低于金属沉积期（P=0.011）和纤维损伤期（P=0.023）。纤维损伤期 WD 患者 NOS（P=0.039）和 NO（P=0.047）含量高于正常对照组，而神经元坏死期 GSH-PX（P=0.025）和 CAT（P=0.041）含量较低。在神经元坏死期，IL-1（P=0.030）和 TNF-α 水平高于正常对照组（P=0.042）。纤维损伤（P=0.013）和神经元损伤患者的神经症状评分高于金属沉积患者（P=0.026）。