Page 40 - 《中国药房》2022年8期

槲皮素-白蛋白纳米粒的制备及其对NASH肝纤维化的体内外抑

制作用 Δ

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陈紫莹 ，张 薇 ，覃 萍 ，陈永苗 ，张传平 ，李俊伟 ，陈阿丽 （1.广东药科大学医药化工学院，广州
510006；2.广东药科大学附属第一医院药学部，广州 501080；3.广州白云山和记黄埔中药有限公司，广州
510515）
中图分类号 R943；R965 文献标志码 A 文章编号 1001-0408（2022）08-0930-07
DOI 10.6039/j.issn.1001-0408.2022.08.05
摘 要 目的 制备槲皮素-白蛋白纳米粒（Que-HSA-NPs），并评价Que-HSA-NPs对非酒精性脂肪性肝炎（NASH）肝纤维化的体内
外抑制作用。方法 运用去溶剂化-化学交联法制备Que-HSA-NPs，观察其外观特征并检测其粒径、多分散指数（PDI）、Zeta电位和
载药量。将槲皮素（Que）和Que-HSA-NPs作用于鼠源HSC-T6细胞，比较两者对细胞存活率及对转化生长因子β（TGF-β）、Ⅰ型胶
原α1（COL1A1）和α-平滑肌肌动蛋白（α-SMA）mRNA表达的影响。将Que和Que-HSA-NPs作用于经低蛋氨酸和胆碱缺乏高脂鼠
粮喂养的小鼠，通过测定其血清肝损伤指标水平，肝组织病理学特征，肝组织中TGF-β、COL1A1、α-SMA mRNA表达以及肝组织
中α-SMA蛋白表达的变化来评价两者对小鼠NASH肝纤维化的改善作用。结果 所制Que-HSA-NPs呈球形，粒径为（172.9±2.2）
nm，PDI为0.233，Zeta电位为－29.2 mV，载药量为2.99％。0～250 μg/mL的Que和Que-HSA-NPs对HSC-T6细胞无毒，两者均能
显著降低细胞中TGF-β、COL1A1和α-SMA mRNA的表达，且Que-HSA-NPs的作用更强（P＜0.05）。两者均能显著降低模型小鼠
血清中肝损伤指标水平，减轻肝损伤，下调肝组织中TGF-β、COL1A1、α-SMA mRNA和α-SMA蛋白的表达，且Que-HSA-NPs的作
用更具优势（P＜0.05）。结论 本研究成功制备了Que-HSA-NPs，并证实其抗NASH肝纤维化的药效优于Que。
关键词 槲皮素；槲皮素-白蛋白纳米粒；非酒精性脂肪性肝炎；肝纤维化；体内外研究

Preparation of quercetin-human serum albumin-nanoparticles and its inhibitory effects against NASH-
induced liver fibrosis in vivo and in vitro
CHEN Ziying ，ZHANG Wei ，QIN Ping ，CHEN Yongmiao ，ZHANG Chuanping ，LI Junwei ，CHEN Ali 1
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（1. School of Chemistry and Chemical Engineering， Guangdong Pharmaceutical University， Guangzhou
510006，China；2. Dept. of Pharmacy，the First Affiliated Hospital of Guangdong Pharmaceutical University，
Guangzhou 501080， China；3. Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company
Limited，Guangzhou 510515，China）
ABSTRACT OBJECTIVE To prepare quercetin-human serum albumin-nanoparticles（Que-HSA-NPs），and to evaluate the in
vivo and in vitro inhibitory effects of Que-HSA-NPs on hepatic fibrosis of non-alcoholic steatohepatitis （NASH）. METHODS
Que-HSA-NPs were prepared by desolvation-chemical cross-linking method，their appearance characteristics were observed，and
their particle size，polydispersity index（PDI），Zeta potential and drug loading were detected. Quercetin（Que）and Que-HSA-NPs
were applied to murine HSC-T6 cells. The effects of them on survival rate of HSC-T6，mRNA expression of transforming growth
factor β（TGF-β），Type Ⅰ collagen α1（COL1A1）and α-smooth muscle actin（α-SMA）were compared. Que and Que-HSA-NPs
were applied to mice fed with low methionine and choline deficient high-fat diet. The serum levels of liver injury indexes，liver
pathological characteristics，mRNA expressions of TGF-β，COL1A1 and α-SMA，protein expression of α-SMA in liver tissue were
determined to evaluate the improvement effects of them on hepatic fibrosis of NASH in mice. RESULTS The prepared
Que-HSA-NPs was spherical，the particle size was（172.9±2.2）nm，the PDI was 0.233，the Zeta potential was －29.2 mV，and
the drug loading was 2.99％. Que and Que-HSA-NPs were nontoxic to HSC-T6 at concentrations of 0-250 μg/mL. Both of them
could significantly decrease mRNA expressions of TGF-β，COL1A1 and α-SMA，especially Que-HSA-NPs（P＜0.05）. They also
could significantly decrease the serum levels of liver injury index，relieve liver injury and down-regulate mRNA expressions of
TGF-β，COL1A1 and α-SMA and protein expression of α-SMA，
Δ 基金项目：国家自然科学基金资助项目（No.82104382）；广东省
especially Que-HSA-NPs （P＜0.05）. CONCLUSIONS Que-
基础与应用基础研究基金项目（No.2019A1515011726）；广东高校教师
HSA-NPs is successfully prepared，and confirm that its anti-
特色创新研究项目（No.2020SWYY05） NASH hepatic fibrosis effect is better than that of Que.
＊硕士研究生。研究方向：药品检验与分析。E-mail：577368765@
KEYWORDS quercetin；quercetin-human serum albumin-
qq.com
nanoparticles；non-alcoholic steatohepatitis；hepatic fibrosis；
# 通信作者：高级实验师，硕士生导师。研究方向：中药药效物质
基础及新药开发。电话：020-39352553。E-mail：chenali2004@163.com inhibitory effect in vivo and in vitro study

·930 · China Pharmacy 2022 Vol. 33 No. 8 中国药房 2022年第33卷第8期