摘要
目的 探讨姜黄素经巨噬细胞极化对镉促进小鼠动脉粥样硬化的保护作用,并初步揭示该效应是否与Janus蛋白酪氨酸激酶2/信号转导和转录激活子3(Janus kinase 2/signal transducer and activator of transcription 3,JAK2/STAT3)信号通路有关。方法 60只SPF级ApoE^(-/-)雄鼠随机分为4组:对照组、姜黄素组(100 mg/kg·bw)、氯化镉组(100 mg/L CdCl_(2))和姜黄素+CdCl_(2)组。干预12周后,观察小鼠主动脉斑块形成情况,检测主动脉巨噬细胞极化情况及JAK2/STAT3信号通路分子变化情况,测量小鼠血浆血脂、炎性因子及血管细胞黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)含量。另使用姜黄素(3.0μmol/L)和CdCl_(2)(3.0μmol/L)处理小鼠巨噬细胞RAW264.7,检测细胞极化情况以及胞内JAK2/STAT3信号通路分子变化情况。结果 与CdCl_(2)组相比,姜黄素可减轻小鼠主动脉斑块形成,升高血浆高密度脂蛋白(High-density lipoprotein,HDL)水平(t=5.311,P<0.01)并降低VCAM-1(t=4.324,P<0.05)。姜黄素可抑制CdCl_(2)对小鼠主动脉巨噬细胞M1型极化的促进作用,表现为CD86^(+)细胞数量减少(t=5.178,P<0.05)以及M1型巨噬细胞特征性细胞因子肿瘤坏死因子-α(t=8.065,P<0.01)、白细胞介素-6(t=5.703,P<0.01)含量降低。与此同时,姜黄素还能减轻CdCl_(2)对RAW264.7细胞向M1型极化的促进作用。动物实验和细胞实验均观察到姜黄素能抑制CdCl_(2)对JAK2、STAT3表达量和磷酸化水平的上调作用。结论 姜黄素可通过抑制巨噬细胞M1型极化减轻镉对小鼠动脉粥样硬化的促进作用,该效应可能与JAK2/STAT3信号通路的抑制有关。
Objective To investigate the protective effect of curcumin on cadmium-promoted atherosclerosis by regulating macrophage polarization in mice and whether the protective effect is related to the JAK2/STAT3 signaling pathway.Methods Sixty SPFgrade ApoE-/-male mice were randomly divided into four groups:control group,curcumin group(100 mg/kg·bw),cadmium chloride group(100 mg/L,CdCl_(2)),and curcumin+CdCl 2 group.After 12 weeks of intervention,the formation of aortic plaques in mice was observed.The polarization of aortic macrophages and JAK2/STAT3 signaling pathway molecules were detected.The levels of plasma lipids,inflammatory factors,and vascular cell adhesion molecule-1(VCAM-1)were measured.In vitro,RAW264.7 cells were treated with curcumin(3.0μmol/L)and CdCl 2(3.0μmol/L),and cell polarization and intracellular JAK2/STAT3 signaling pathway molecules were detected.Results Compared with the CdCl 2 group,curcumin alleviated the formation of aortic plaques in mice,increased plasma HDL(t=5.311,P<0.01),but reduced VCAM-1(t=4.324,P<0.05).Curcumin inhibited the promoting effect of CdCl 2 on M1 polarization of aortic macrophages in mice,manifesting as decreases in the number of CD86+cells(t=5.178,P<0.05)and plasma levels of characteristic factors of M1-type macrophages including tumor necrosis factor-α(t=8.065,P<0.01)and interleukin-6(t=5.703,P<0.01).Meanwhile,curcumin alleviated the promoting effect of CdCl 2 on the M1 polarization of RAW264.7 cells.Finally,curcumin could inhibit the upregulation of CdCl 2 on the expression and phosphorylation levels of JAK2 and STAT3 in vivo and in vitro.Conclusion Curcumin alleviates the promoting effect of cadmium on atherosclerosis by inhibiting M1 polarization of macrophages,which may be related to the inhibition of the JAK2/STAT3 signaling pathway.
作者
赵晓晗
万宇
莫丽芬
黄海斌
朱伟
杨光宇
杨杏芬
宋佳
ZHAO Xiao-han;WAN Yu;MO Li-fen;HUANG Hai-bin;ZHU Wei;YANG Guang-yu;YANG Xing-fen;SONG Jia(Food Safety and Health Research Center,NMPA Key Laboratory for Safety Evaluation of Cosmetics,GuangdongHongkong-Macao Joint Laboratory for Contaminants Exposure and Health,Guangdong Provincial Key Laboratory of Tropical Disease Research,School of Public Health,Southern Medical University,Guangzhou,Guangdong 510515,China;Guangzhou Center for Disease Control and Prevention,Guangzhou,Guangdong 510440,China)
出处
《毒理学杂志》
2025年第2期79-88,共10页
Journal of Toxicology
基金
国家自然科学基金(82073599,82373600)。
