[1]李钰婷,蔡大可,郑柳怡,等.NLRP3基因敲除增强芹菜素对triton-WR 1339所致高脂血症的降血脂及抗炎作用研究[J].中国药理学通报,2020,(04):543-549.[doi:10.3969/j.issn.1001-1978.2020.04.018]
 LI Yu-ting,CAI Da-ke,ZHENG Liu-yi,et al.Knockout of NLRP3 enhances hypolipidemic effect and anti-inflammative effect of apigenin in Triton-WR 1339-induced hyperlipidemia mice[J].Chinese Pharmacological Bulletin,2020,(04):543-549.[doi:10.3969/j.issn.1001-1978.2020.04.018]
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NLRP3基因敲除增强芹菜素对triton-WR 1339所致高脂血症的降血脂及抗炎作用研究()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2020年04期
页码:
543-549
栏目:
论著
出版日期:
2020-04-07

文章信息/Info

Title:
Knockout of NLRP3 enhances hypolipidemic effect and anti-inflammative effect of apigenin in Triton-WR 1339-induced hyperlipidemia mice
文章编号:
1001-1978(2020)04-0543-07
作者:
李钰婷123蔡大可23 郑柳怡123胡子旋23占心佾123刘昌辉4甘海宁23黄雪君23黄丹娥23陈玉兴23
1. 广州中医药大学第五临床医学院,广东 广州 510405; 2. 广东省中医药工程技术研究院, 广东 广州 510095; 3. 广东省中医药研究开发重点实验室,广东 广州 510095; 4. 广州中医药大学临床药理研究所, 广东 广州 510405
Author(s):
LI Yu-ting123CAI Da-ke23ZHENG Liu-yi123HU Zi-xuan23ZHAN Xin-yi123LIU Chang-hui4GAN Hai-ning23HUANG Xue-jun23HUANG Dan-e23 CHEN Yu-xing
1.Guangzhou University of Chinese Medicine, Guangzhou 510405,China; 2.Guangdong Province Engineering Technology Research Institute of Chinese Medicine, Guangzhou 510095, China; 3.Guangdong Provincial Key Labof Research and Development in Traditional Chinese Medicine, Guangzhou 510095, China; 4. Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine,Guangzhou 510405,China
关键词:
NLRP3 芹菜素 降血脂 抗炎 triton-WR 1339 CYP7A1 FGF21
Keywords:
NLRP3 apigenin hypolipedemia anti-inflammation triton-WR 1339 CYP7A1 FGF21
分类号:
R-332; R284.1; R322.47; R364.5; R394.2; R589.202.2; R977.6
DOI:
10.3969/j.issn.1001-1978.2020.04.018
文献标志码:
A
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。
Abstract:
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.

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备注/Memo

备注/Memo:
收稿日期:2019-10-28,修回日期:2019-12-30
基金项目:国家自然科学基金资助项目(No 81973508,81773969)
作者简介:李钰婷(1995-),女,硕士生,研究方向:中药药理,E-mail:335228256@qq.com;
陈玉兴(1971-),男,教授,硕士生导师,研究方向:中药药理及新药开发,通讯作者,E-mail:cyx89333@qq.com
更新日期/Last Update: 2020-04-07