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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
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| 篇名： | 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 |
| TITLE： | Preparation of quercetin-human serum albumin-nanoparticles and its inhibitory effects against NASH-induced liver fibrosis in vivo and in vitro |
| 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-SMAmRNA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－29.2mV，载药量为2.99％。0～250μg/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-SMAmRNA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-SMAmRNA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。 |
| 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-T 6 cells. The effects of them on survival rate of HSC-T 6，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-T 6 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 inju ry index ，relieve liver injury and down-regulate mRNA expressions of TGF-β，COL1A1 and α-SMA and protein expression of α-SMA， especially Que-HSA-NPs （P＜0.05）. CONCLUSIONS Que- HSA-NPs is successfully prepared ，and confirm that its anti- NASH hepatic fibrosis effect is better than that of Que . |
| 期刊： | 2022年第33卷第08期 |
| 作者： | 陈紫莹，张薇，覃萍，陈永苗，张传平，李俊伟，陈阿丽 |
| AUTHORS： | CHEN Ziying，ZHANG Wei，QIN Ping，CHEN Yongmiao，ZHANG Chuanping，LI Junwei，CHEN Ali |
| 关键字： | 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 |
| KEYWORDS： | quercetin；quercetin-human serum albumin- |
| 阅读数： | 865 次 |
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