中国中西医结合杂志2025，Vol.45Issue(5)：578-583,6.DOI:10.7661/j.cjim.20250303.128
基于胆固醇外流探讨黄芩苷调控NLRP3/caspase-1/GSDMD改善动脉粥样硬化
Exploring the Role of Baicalin in Regulating NLRP3/caspase-1/GSDMD in Atherosclerosis Based on Cholesterol Efflux
摘要
Abstract
Objective To investigate the role and mechanism of baicalin in regulating the NOD-like receptor 3(NLRP3)/cysteinyl aspartate specific proteinase 1(caspase-1)/gasdermin D(GSDMD)pathway to mediate cholesterol efflux to improve atherosclerosis(AS).Methods Totally 30 ApoE-/-AS mice were randomly divided into model group,baicalin group and simvastatin group,10 in each group.And 10 C57BL/6J mice were recruited as the control group.The model and drug intervention groups were fed with high-fat diet,while the control group was fed with normal diet.Eight weeks later,the baicalin group was gavaged with baicalin 50 mg·kg-1·d-1,and the simvastatin group was gavaged with simvastatin 2.275 mg·kg-1·d-1.The control group and model group were gavaged with an equal volume of saline.The intervention was carried out for 4 weeks.Automatic biochemistry analyser was used to detect the total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)in serum.HE staining was used to observe the lipid deposition in the aorta.Transmission electron microscopy was used to observe the ultrastructure of the aorta.ELISA was used to detect the content of serum reactive oxygen species(ROS).Immunohistochemical assay was used to detect the CD36,peroxisome proliferator-activated receptor γ(PPARγ)and ATP-binding cassette transporter A1(ABCA1)in aorta.RT-qPCR and Wes automatic protein analyser were used to detect the mRNA and protein expression of NLRP3,caspase-1 and GSDMD in aorta.Results In the control group,the aortic intima was smooth with no lipid deposition was seen,and the cell membrane of endothelial cells was intact.While in the model group,the aortic intima was markedly elevated with plaques with a large number of cholesterol crystals gathered in needle-like voids around the foam cells,endothelial cells were swollen,and the structure of the peritoneal membrane was incomplete with the formation of bubble-like protrusions,and the number of mitochondria was reduced.In the baicalin group and the simvastatin group,almost no plaque was formed,the endothelial cells and mitochondria had improved significantly compared with those in the model group,the endothelial cells and mitochondria were almost free of plaque formation.Compared with the control group,TC,TG,LDL-C level and ROS content in serum,aortic CD36 protein expression,the mRNA and protein expression of NLRP3,caspase-1,GSDMD were increased,while the HDL-C levels in serum,aortic PPARγ,ABCA1 protein expression were reduced in the model group(P＜0.01).Compared with the model group,the TC,TG,LDL-C level,ROS content in serum,aortic CD36 protein,the mRNA and protein expression of NLRP3,caspase-1,GSDMD were reduced(P＜0.05,P＜0.01),while the HDL-C level in serum,aortic PPARγ,and ABCA1 protein expression were increased in the baicalin and simvastatin groups(P＜0.05,P＜0.01).Conclusions Baicalin has the effect of reducing aortic lipid deposition and improving atherosclerosis.Its mechanism may be related to the promotion of macrophage cholesterol efflux and the inhibition of the NLRP3/caspase-1/GSDMD pyroptosis pathway.关键词
黄芩苷/动脉粥样硬化/胆固醇逆转运/NLRP3/caspase-1/GSDMD信号通路/细胞焦亡Key words
baicalin/atherosclerosis/cholesterol reverse transport/NLRP3/caspase-1/GSDMD signalling pathway/pyroptosis引用本文复制引用
于宁,宋囡,曹媛,贾连群..基于胆固醇外流探讨黄芩苷调控NLRP3/caspase-1/GSDMD改善动脉粥样硬化[J].中国中西医结合杂志,2025,45(5):578-583,6.基金项目
国家自然科学基金面上项目(No.82074145,No.82374423) （No.82074145,No.82374423）
