摘要
目的探讨阿托伐他汀钙(atorvastatin calcium salt trihydrate,ATV)在人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)中对富含半胱氨酸型运动神经元蛋白1(Crim1)和炎症因子的调控作用,初步研究Crim1影响动脉粥样硬化发生、发展的具体机制。方法通过实时定量PCR和免疫印迹分析探讨ATV对HUVECs炎症的影响和机制。此外,还采用免疫组织化学方法分析了Crim1在动脉粥样硬化斑块中的表达。结果免疫组织化学分析结果显示,与正常内膜组织相比,Crim1的mRNA和蛋白质水平在动脉粥样硬化斑块中显著上调(P<0.001)。生物信息学分析显示Crim1与白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和核因子-κB(nuclear factor-κB,NF-κB)存在共表达关系。实验结果显示ATV能显著下调Crim1的mRNA和蛋白质水平,并降低IL-6、TNF-α和NF-κB的表达,抑制炎症反应。此外,siRNA敲减Crim1可显著抑制IL-6、TNF-α和NF-κB的表达,重组质粒pcDNA过表达Crim1可显著上调IL-6、NF-α和NF-κB的表达,分组干预实验结果显示ATV能减弱Crim1对炎症因子的诱导作用。结论ATV介导Crim1抑制内皮细胞炎症,从而为ATV用于非降脂功能提供了新的前景,并为动脉粥样硬化的预防和治疗提供了新方向。
Objective To investigate the regulatory effects of atorvastatin calcium salt trihydrate(ATV)on cycteine-rich motor neuron 1(Crim1)and inflammatory cytokines in human umbilical vein endothelial cells(HUVECs),and to provide a preliminary study on the effect of Crim1 on atherosclerosis.Methods Real-time quantitative PCR(qRT-PCR)and Western blot analysis were used to explore the effects of ATV on inflammation in HUVECs.Immunohistochemistry was employed to analyze Crim1 expression in atherosclerotic plaques.Results Immunohistochemical analysis revealed that compared with normal endothelial tissue,the mRNA and protein levels of Crim1 were significantly upregulated in atherosclerotic plaques(P<0.001).Bioinformatics analysis showed a co-expression relationship between Crim1 and interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and nuclear factor-κB(NF-κB).Experimental results demonstrated that ATV significantly downregulated Crim1 mRNA and protein levels,and reduced the expression of IL-6,TNF-α,and NF-κB,thereby inhibiting the inflammatory response.Furthermore,siRNA-mediated silencing of Crim1 significantly inhibited the expression of IL-6,TNF-α,and NF-κB.Overexpression of Crim1 using the recombinant plasmid pcDNA led to a significant increase in IL-6,TNF-α,and NF-κB expression.Group intervention experiments showed that ATV attenuated the inflammatory effects induced by Crim1.Conclusion The results indicate that ATV mediates the suppression of endothelial cell inflammation via Crim1,providing new insights into the non-lipid-lowering functions of ATV.This study also offers a novel direction for the prevention and treatment of atherosclerosis.
作者
刘雪辉
吴丽美
刘达彬
陈旗军
况璐
刘华森
伍绍国
LIU Xue-hui;WU Li-mei;LIU Da-bin;CHEN Qi-jun;KUANG Lu;LIU Hua-sen;WU Shao-guo(Department of Clinical Laboratory,Guangzhou Twelfth People′s Hospital,Guangzhou 510620,Guangdong,China;不详)
出处
《广东医学》
2025年第2期193-200,共8页
Guangdong Medical Journal
基金
广东省自然科学基金项目(2023A1515010453)
广州市科技计划项目(2025A03J3440,2023A03J0492,2023A03J0976)
广州市卫生健康科技项目(20231A011060)。
