Tao Zhuang, Kang Shuai, Liu Jipeng, Wang Rui, Zhou Jiafeng, Yang Wenming, Wang Meixia
First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China.
Graduate School, Anhui University of Chinese Medicine, Hefei, Anhui, China.
Medicine (Baltimore). 2024 Nov 22;103(47):e40598. doi: 10.1097/MD.0000000000040598.
This study investigates levels of cuproptosis markers in Wilson disease (WD) and their role in the occurrence and development of WD. We retrospectively collected clinical data from 76 patients with Leipzig score ≥ 4 hospitalized in the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2023 to September 2023. The participants were given copper chelators (sodium dimercaptosulphonate (20 mg·kg-1), 4 courses of treatment, 32 days). The levels of clinical indicators (ALT, AST, ALP, HA, LN, PIIINP, CIV, liver stiffness measurement, United Wilson disease rating scale), oxidative stress indexes (SOD, MDA, GSH), cuproptosis markers (FDX1, DLAT, LIAS, ACO-2, SDHB, PLOD1, DPYD) of the participants were measured before and after treatment. Compared with the control group, FDX1, DLAT, DPYD, and POLD1 in WD were significantly up-regulated before treatment (6464.34 ± 2980.66 vs 4125.43 ± 2230.13 pg ⋅ mL-1, P < .001, 1364.36 ± 376.81 vs 884.22 ± 175.42 pg ⋅ mL-1, P < .001, 279.74 ± 123.63 vs 155.68 ± 67.32 pg ⋅ mL-1, P < .001, 3536.11 ± 1404.83 vs 1487.76 ± 658.26 pg ⋅ mL-1, P < .001), while SDHB was significantly down-regulated (2458.75 ± 1103.75 vs 5338.22 ± 921.54 pg ⋅ mL-1, P < .05). SOD was significantly down-regulated before treatment (13.20 ± 2.06 vs 13.27 ± 1.79 U ⋅ mgprot-1, P < .05), while MDA and GSH were significantly up-regulated (10.53 ± 4.76 vs 4.92 ± 1.81 nmol ⋅ mL-1, P < .001, 49.28 ± 25.55 vs 24.70 ± 12.01 µol ⋅ L-1, P < .001). POLD1 were down-regulated (3536.11 ± 1404.83 vs 1487.76 ± 658.26 pg ⋅ mL-1, P < .001), and SDHB was up-regulated after treatment (2458.75 ± 1103.75 vs2709.61 ± 906.95 pg ⋅ mL-1, P < .05), while SOD, MDA and GSH were significantly down-regulated (13.20 ± 2.06 vs 12.48 ± 1.52 U ⋅ mgprot-1, P < .05, 10.53 ± 4.76 vs 7.65 ± 3.65 nmol ⋅ mL-1, P < .001, 49.28 ± 25.55 vs 34.09 ± 15.02 µmol ⋅ L-1, P < .001). The expression levels of cuproptosis markers and oxidative stress indexes are abnormal in WD patients. However, chelation therapy can improve the recovery of cuproptosis markers, oxidative stress indexes, and hepatic fibrosis indexes.
本研究调查了威尔逊病（WD）中铜死亡标志物的水平及其在WD发生发展中的作用。我们回顾性收集了2023年1月至2023年9月在安徽中医药大学第一附属医院住院的76例莱比锡评分≥4的患者的临床资料。参与者接受了铜螯合剂（二巯基磺酸钠（20 mg·kg-1），4个疗程，共32天）治疗。在治疗前后测量参与者的临床指标（谷丙转氨酶、谷草转氨酶、碱性磷酸酶、透明质酸、层粘连蛋白、Ⅲ型前胶原氨基端肽、Ⅳ型胶原、肝脏硬度值、威尔逊病综合评分量表）、氧化应激指标（超氧化物歧化酶、丙二醛、谷胱甘肽）、铜死亡标志物（铁硫簇组装蛋白1、二氢硫辛酸转乙酰基酶、赖氨酸丙二酸单酰基转移酶、顺乌头酸酶2、琥珀酸脱氢酶黄素蛋白亚基、脯氨酰羟化酶结构域蛋白1、二氢嘧啶脱氢酶）的水平。与对照组相比，WD患者治疗前铁硫簇组装蛋白1、二氢硫辛酸转乙酰基酶、二氢嘧啶脱氢酶和脯氨酰羟化酶结构域蛋白1显著上调（6464.34±2980.66 vs 4125.43±2230.13 pg⋅mL-1，P<.001；1364.36±376.81 vs 884.22±175.42 pg⋅mL-1，P<.001；279.74±123.63 vs 155.68±67.32 pg⋅mL-1，P<.001；3536.11±1404.83 vs 1487.76±658.26 pg⋅mL-1，P<.001），而琥珀酸脱氢酶黄素蛋白亚基显著下调（2458.75±1103.75 vs 5338.22±921.54 pg⋅mL-1，P<.05）。治疗前超氧化物歧化酶显著下调（13.20±2.06 vs 13.27±1.79 U⋅mgprot-1，P<.05），而丙二醛和谷胱甘肽显著上调（10.53±4.76 vs 4.92±1.81 nmol⋅mL-1，P<.001；49.28±25.55 vs 24.70±12.01 µmol⋅L-1，P<.001）。治疗后脯氨酰羟化酶结构域蛋白1下调（3536.11±1404.83 vs 1487.76±658.26 pg⋅mL-1，P<.001），琥珀酸脱氢酶黄素蛋白亚基上调（2458.75±1103.75 vs 2709.61±906.95 pg⋅mL-1，P<.05），而超氧化物歧化酶、丙二醛和谷胱甘肽显著下调（13.20±2.06 vs 12.48±1.52 U⋅mgprot-1，P<.05；10.53±4.76 vs 7.
