Zhang Huaixuan, Wu Xueting, Wang Yue, Yang Zhongling, Dai Yaqian, Shuai Zongwen
Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
Inflammopharmacology. 2025 Apr 17. doi: 10.1007/s10787-025-01735-9.
To explore the potential combined effects of hydroxycholoroquine (HCQ) and its metabolites on blood lipids and glucose in the treatment of rheumatoid arthritis (RA).
In the HCQ group, the concentrations of HCQ and its metabolites, including desethylhydroxychloroquine (DHCQ), esethylchloroquine (DCQ) and bisdesethylchloroquine (BDCQ), were detected by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The relationships between the levels of blood lipid and glucose and concentrations of HCQ and its metabolites were also analysed. Further, a multiple regression model was employed to evaluate the actual roles of HCQ and its metabolites in various factors affecting blood lipids and glucose.
Significant higher high-density lipoprotein cholesterol (HDL) and lower low-density lipoprotein cholesterol (LDL) are found in the HCQ group than in the control group [1.63 ± 0.39 mmol/l vs. 1.39 ± 0.35 mmol/l, p < 0.001; 2.15 (1.80, 2.81) mmol/l vs. 2.54 (2.24, 3.10) mmol/l, p = 0.017, respectively]. Multivariate regression analysis indicates only HCQ concentration might act as an independent factor influencing the levels of HDL, VLDL, and TG in RA patients.
HCQ might increase HDL level and reduce LDL, VLDL, TC, and TG levels in RA treatment. These beneficial effects on modifying lipid profile might be counteracted to various degrees by some of its metabolites (DHCQ and BDCQ). Therefore, for RA patients with HCQ in their treatment regime, it might facilitate the improvement of lipids profile by promoting the excretion of HCQ metabolites. This study did not demonstrate the significant hypoglycemic effect of HCQ and its metabolites.
探讨羟氯喹（HCQ）及其代谢产物在类风湿关节炎（RA）治疗中对血脂和血糖的潜在联合作用。
在HCQ组中，采用高效液相色谱-串联质谱法（HPLC-MS/MS）检测HCQ及其代谢产物的浓度，包括去乙基羟氯喹（DHCQ）、去乙基氯喹（DCQ）和双去乙基氯喹（BDCQ）。分析血脂和血糖水平与HCQ及其代谢产物浓度之间的关系。此外，采用多元回归模型评估HCQ及其代谢产物在影响血脂和血糖的各种因素中的实际作用。
HCQ组的高密度脂蛋白胆固醇（HDL）显著高于对照组，低密度脂蛋白胆固醇（LDL）显著低于对照组[分别为1.63±0.39 mmol/l对1.39±0.35 mmol/l，p<0.001；2.15（1.80，2.81）mmol/l对2.54（2.24，3.10）mmol/l，p=0.017]。多变量回归分析表明，只有HCQ浓度可能是影响RA患者HDL、极低密度脂蛋白（VLDL）和甘油三酯（TG）水平的独立因素。
在RA治疗中，HCQ可能会提高HDL水平，降低LDL、VLDL、总胆固醇（TC）和TG水平。其代谢产物（DHCQ和BDCQ）可能会在不同程度上抵消这些对改善血脂谱的有益作用。因此，对于接受HCQ治疗的RA患者，促进HCQ代谢产物的排泄可能有助于改善血脂谱。本研究未证明HCQ及其代谢产物有显著的降血糖作用。
