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·446 · 南 京 医 科 大 学 学 报 2024年4月

control group. During the administration period，monitoring of rat body weight and food intake was conducted. After continuing feeding
for 8 weeks，serum levels of total cholesterol（TC），triglycerides（TG），low⁃density lipoprotein cholesterol（LDL⁃C），high⁃density
lipoprotein cholesterol（HDL⁃C），alanine aminotransferase（ALT），aspartate aminotransferase（AST），as well as changes in TC and TG
content in liver tissue of each group were detected. Histopathological changes in rat liver tissue were observed by hematoxylin⁃eosin
（HE）staining，oil red O staining，and Masson’s staining. Blood glucose levels were measured using a glucometer，and rat glucose
tolerance was assessed by glucose tolerance test. Fasting insulin levels in each group of rats were detected using enzyme ⁃ linked
immunosorbent assay（ELISA）kits. Real⁃time fluorescent quantitative PCR was used to detect the expression changes of ERS⁃related
genes Bip，Atf6，Atf4，Xbp⁃1s，and Chop in rat liver tissue of each group. Western blot was used to detect the expression changes of ERS⁃
related proteins BiP，CHOP，ATF4，ATF6，XBP⁃1s，and XBP⁃1u in rat liver tissue of each group. Results：Throughout the experiment，
no significant differences in food intake and body weight were observed among the four groups. Compared to the control group，the HFD
group exhibited increased serum levels of triglycerides（TG），total cholesterol（TC），low⁃density lipoprotein⁃ cholesterol（LDL⁃C），
glutamic oxalacetic transaminase（AST），and glutamic⁃pyruvic transaminase（ALT），along with decreased high⁃density lipoprotein⁃
cholesterol（HDL⁃C）levels（P < 0.05）. In the low⁃dose Que group，serum levels of TG，TC，LDL⁃C，AST，and ALT were significantly
reduced compared to the HFD group（P < 0.05）. Similarly，the high⁃dose Que group showed decreased serum levels of TG，TC，AST，
and ALT compared to the HFD group（P < 0.05）. In the HFD group，the liver exhibited enlargement and increased absolute weight，
with prominently swollen hepatocytes，marked vacuolization，and accumulated lipid droplets. Additionally，increased collagen
deposition，insulin resistance，and impaired glucose tolerance were observed in the HFD group. However，these alterations were
reversed in both low⁃and high⁃dose Que groups. The results of RT⁃qPCR and Western blot showed that compared to the control group，
the mRNA expression of Bip，Atf6，Atf4，Xbp⁃1s，and Chop in the liver tissue of rats in the HFD group significantly increased，and the
protein expression of BiP，CHOP，ATF4，ATF6，and XBP⁃1s also significantly increased. Compared to the HFD group，the mRNA
expression of Bip，Atf6，Atf4，Xbp⁃1s，and Chop in the liver tissue of rats in the low⁃ and high⁃dose Que groups decreased，and the
protein expression of BiP，CHOP，ATF4，ATF6，and XBP⁃1s also significantly decreased. Conclusion：Que treatment attenuates
HFD⁃induced aberrant lipid metabolism，impaired glucose tolerance，and hepatic lipid deposition in NAFLD rats，with modulation of
the ERS⁃related pathway potentially playing a critical role.
［Key words］ non⁃alcoholic fatty liver disease；endoplasmic reticulum stress；quercetin
［J Nanjing Med Univ，2024，44（04）：445⁃454］

非酒精性脂肪肝（non⁃alcoholic fatty liver disease， 用目前少有报道，本课题组前期研究发现对ERS调
［6］
NAFLD）是指没有过多饮酒，但肝细胞出现以脂质 控可明显改善 NAFLD 大鼠肝细胞脂毒性损伤 。
沉积和脂肪变性为特征的一种临床病理综合征。 因此，本研究利用高脂饲料喂养（high fat diet，HFD）
目前我国 NAFLD 平均患病率高达 29%，且患者通 建立 NAFLD 大鼠模型，探讨 Que 是否可通过调控
常伴随 2 型糖尿病、肥胖、心血管疾病等慢性相关 ERS信号通路从而改善NAFLD，为 Que 治疗 NAFLD
疾病 。目前认为 NAFLD 的发生取决于多种因素 相关机制研究提供实验基础和理论依据。
［1］
的综合作用，如脂代谢异常、内质网应激（endoplasmic 1 材料和方法
reticulum stress，ERS）、氧化应激、线粒体失功能、炎
症等。其中，ERS被认为是NAFLD发展过程中最重 1.1 材料
要的因素之一 。 1.1.1 动物
［2］
槲皮素（quercetin，Que）是一种天然黄酮类化 SPF 级健康雄性 SD 大鼠 26 只（180~200 g）购
合物，是众多中草药发挥生物学治疗效应的主要成 买于成都达硕实验动物有限公司，经检验合格后饲
分，如柴胡、桑叶和银杏等 。Que对多种疾病具有预 养于贵州中医药大学实验动物中心，条件为：室温
［3］
防和治疗作用，其机制体现为抗氧化、抗炎、抗癌和提 20~25 ℃，湿度 70%，分笼饲养，自由饮食饮水，12 h
高免疫力等 。有研究表明，Que对NAFLD体内外模 明暗交替。实验所用大鼠专用高脂饲料购于成都
［4］
型具有明显的干预作用，涉及的机制主要包括抑 达硕实验动物有限公司。本研究获得贵州中医药
制炎症、氧化应激、凋亡以及对自噬的调控 。然 大学动物保护伦理委员会的批准（实验伦理号：
［5］
而，Que 对 NAFLD 模型下 ERS 相关通路的调控作 20220058）。