Page 56 - 《中国药房》2022年19期

龙胆环烯醚萜类成分对 NAFLD 细胞模型脂质积累及炎症的改

善作用及机制 Δ

王丽娟 ，翁丽丽 ，肖春萍，于 前，寇柏鑫（长春中医药大学药学院，长春 130117）
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中图分类号 R965 文献标志码 A 文章编号 1001-0408（2022）19-2354-05
DOI 10.6039/j.issn.1001-0408.2022.19.10

摘 要 目的 研究龙胆环烯醚萜类成分（gentian iridoids，GI）对非酒精性脂肪性肝病（NAFLD）细胞模型脂质积累及炎症的改善
作用及机制。方法 以游离脂肪酸（0.5 mmol/L）诱导的人肝癌HepG2细胞为NAFLD细胞模型。考察不同浓度（0.125、0.25、0.5、
1、2、4 mg/mL）GI对HepG2细胞活力的影响。将HepG2细胞分为对照组、模型组和GI 低、中、高浓度组（0.25、0.5、1 mg/mL），除对
照组外，其余组均加入0.5 mmol/L游离脂肪酸进行造模。培养24 h后，考察HepG2细胞内脂滴形成的情况，检测细胞内三酰甘油
（TG）含量，检测细胞上清液中天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）和炎症指标[白细胞介素1β（IL-1β）、IL-6、肿瘤坏死因
子α（TNF-α）]的水平；检测细胞中固醇调节元件结合蛋白1c（SREBP-1c）、脂肪酸合成酶（FAS）mRNA和核因子κB（NF-κB）信号
通路相关蛋白[ NF-κB抑制蛋白α（IκBα）、NF-κB、磷酸化NF-κB（p-NF-κB）]的表达。结果 HepG2细胞经不同浓度GI作用后，细
胞活力均显著升高（P＜0.01）。与模型组比较，GI各浓度组细胞内红色脂滴明显减少，细胞核萎缩不明显、体积大小正常；细胞内
TG含量（低浓度组除外），细胞上清液中AST、ALT、IL-1β、IL-6（低剂量组除外）、TNF-α水平，细胞中SREBP-1c、FAS mRNA表达
水平以及NF-κB蛋白磷酸化水平均显著降低（P＜0.05或P＜0.01），IκBα蛋白表达水平均显著升高（P＜0.01）。结论 GI可减少
NAFLD细胞模型的脂质积累，减轻炎症反应，其作用机制可能与抑制SREBP-1c/FAS及NF-κB信号通路有关。
关键词 龙胆；环烯醚萜类成分；脂质积累；炎症反应；核因子κB信号通路；非酒精性脂肪性肝病

Improvement effects and mechanism of gentian iridoids on lipid accumulation and inflammation in
NAFLD cell model
WANG Lijuan，WENG Lili，XIAO Chunping，YU Qian，KOU Baixin（School of Pharmacy， Changchun
University of Chinese Medicine，Changchun 130117，China）

ABSTRACT OBJECTIVE To study the improvement effects and mechanism of gentian iridoids（GI）on lipid accumulation and
inflammation in non-alcoholic fatty liver disease（NAFLD）model. METHODS Human hepatoma HepG2 cells induced by free fatty
acids（0.5 mmol/L）were selected as NAFLD cell models. The effects of GI at different concentrations（0.125，0.25，0.5，1，2，4
mg/mL）on HepG2 cell viability were investigated. HepG2 cells were divided into control group，model group and low，medium
and high concentration groups of GI（0.25，0.5 and 1 mg/mL）. Except for control group，0.5 mmol/L free fatty acid was added in
other groups for modeling. After 24 h of culture，the formation of lipid droplets was observed in HepG2 cells；the content of
triglyceride（TG）was detected. The levels of aspartate aminotransferase（AST），alanine aminotransferase（ALT）and inflammation
indexes [interleukin-1 β （IL-1 β），IL-6，tumor necrosis factor α （TNF- α）] in cell supernatant were determined. The mRNA
expressions of sterol-regulatory element binding protein（SREBP-1c）and fatty acid synthase（FAS）as well as the expression of
nuclear factor-κB（NF-κB）related proteins [NF-κB inhibitor protein α（IκBα），NF-κB，phosphorylated NF-κB（p-NF-κB）] were
also detected. RESULTS After treated with different concentrations of GI，the cell viability of HepG2 cells was improved
significantly（P＜0.01）. Compared with model group，the number of red lipid droplets in the cells of each concentration group of
GI was significantly reduced，the nuclear atrophy was not obvious，and the size was normal；the content of TG（except for low
concentration group），and the levels of ALT，AST，IL-1β，IL-6 （except for low concentration group） and TNF- α in cell
supernatant were all decreased significantly；mRNA expression of SREBP-1c and FAS and the phosphorylation level of NF-κB
were also decreased significantly（P＜0.05 or P＜0.01）；the protein expression of IκBα was increased significantly（P＜0.01）.
CONCLUSIONS GI can reduce the lipid accumulation and inflammatory response of NAFLD cell model induced by free fatty
acids，and its mechanism may be related to the inhibition of
Δ 基金项目 吉 林 省 科 技 发 展 计 划 项 目（No. YDZJ202201-
SREBP-1c/FAS and NF-κB signaling pathway.
ZYTS636） KEYWORDS
＊第一作者 博士研究生。研究方向：中药资源、品质评价及开发 Gentiana scabra；gentian iridoids；lipid
利用。E-mail：1575907709@qq.com accumulation；inflammatory response；nuclear factor-κB
# 通信作者 教授，博士生导师。研究方向：中药资源、品质评价及 signaling pathway；non-alcoholic fatty liver disease
开发利用。E-mail：735110462@qq.com

·2354· China Pharmacy 2022 Vol. 33 No. 19 中国药房 2022年第33卷第19期