摘要
目的探讨NLRP3对芹菜素降血脂和抗炎作用的干预及调控机制。方法采用Triton-WR1339对野生型(widetype,WT)C57BL/6小鼠和NLRP3-/-小鼠致高脂血症,给药组连续5 d灌胃给予芹菜素6.25 mg·kg^-1,收集血样及肝脏,测定血清中TC、TG、HDL、LDL;肝脏进行HE染色分析;ELISA测定血清中IL^-1β、IL-6、MCP-1含量。RT-qPCR测定肝脏中NLRP3、IL-4、ASC、CD36、CYP7A1、FGF21的mRNA表达水平。结果与NLRP3-/-模型组相比较,芹菜素降低NLRP3-/-模型小鼠血清TC、TG、LDL-C、IL^-1B、IL-6、MCP-1含量,提高HDL-C含量(P<0.05),减少肝脏脂肪病变比例;芹菜素对WT模型小鼠未见此作用。芹菜素均能上调WT和NLRP3-/-模型小鼠CD36、vLDLR的表达,抑制ASC、IL-4表达(P<0.05)。芹菜素仅调控NLRP3-/-模型小鼠的FGF21、CYP7A1的表达(P<0.05),对WT模型小鼠无作用。结论NLRP3基因敲除增强低剂量芹菜素改善Triton-WR 1339所致的高脂血症及炎症等症状。NLRP3基因敲除增强芹菜素调控血脂作用的机制可能为:NLRP3炎症小体缺失,从而增强芹菜素对FGF21/CYP7A1信号通路的调控相关。
Aim To investigate the role and mechanism of NLRP3 on hypolipidemic effect and anti-inflammative effect of apigenin.Methods Triton-WR 1339-induced hyperlipidemia was applied to wide type C57BL/6 and NLRP3-/-mice,which was treated with apigenin of 6.25 mg·kg^-1·day-1 for five days.Blood and liver tissueswere collected for detecting TC,TG,HDL,LDL,IL^-1B,IL-6,MCP-1 and the liver underwent HE staining.The expressions of NLRP3,IL-4,ASC,CD36,CYP7A1 and FGF21 were tested using RT-qPCR.Results Compared with NLRP3-/-model group,serum contents of TC,TG,HDL,LDL,IL^-1B,IL-6,MCP-1 were reduced in NLPR3-/-treated with apigenin of 6.25 mg·kg^-1(P<0.05).The percentage of hepatic steatosis wasdown-regulated by apigenin in pathogenesis observation.However,all these phenotype changes were not observed in WT mice treated with apigenin.Moreover,up-regulation of CD36 and vLDLR and down-regualtion of ASC and IL-4 were founded in both WT and NLRP3-/-model group(P<0.05),while down-regulation of FGF21 and up-regulation of CYP7A1 were only seen in NLRP3-/-model group but not in WT group.Conclusions Knockout of NLRP3 enhances hypolipidemic effect and anti-inflammative effect of apigenin in triton-1339W-induced hyperlipidemia mice,which may be associated with apigenin-regulated FGF21/CYP7A1 pathway without NLRP3 inflammasome interruption.
作者
李钰婷
蔡大可
郑柳怡
胡子旋
占心佾
刘昌辉
甘海宁
黄雪君
黄丹娥
陈玉兴
LI Yu-ting;CAI Da-ke;ZHENG Liu-yi;HU Zi-xuan;ZHAN Xin-yi;LIU Chang-hui;GAN Hai-ning;HUANG Xue-jun;HUANG Dan-e;CHEN Yu-xing(Guangzhou University of Chinese Medicine, Guangzhou 510405,China;Guangdong Province Engineering Technology Research Institute of Chinese Medicine, Guangzhou 510095, China;Guangdong Provincial Key Labof Research and Development in Traditional Chinese Medicine, Guangzhou 510095, China;Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine,Guangzhou 510405,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2020年第4期543-549,共7页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81973508,81773969)。