摘要
目的探索益气健脾汤对非酒精性脂肪性肝病(NAFLD)小鼠的作用机制。方法将48只C57BL/6J小鼠按照随机数字表法分为空白组、模型组、辛伐他汀组及低、中、高剂量组,各8只。空白组之外的小鼠均给予高脂饮食进行NAFLD造模。造模成功后辛伐他汀组给予辛伐他汀10 mg/(kg·d)灌胃;低、中、高剂量组分别给予益气健脾汤5、10、20 g/(kg·d)灌胃,空白组、模型组给予等量蒸馏水灌胃。治疗4周后使用酶联免疫吸附试验法检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、游离脂肪酸(FFA)、超氧化物歧化酶(SOD);比色法检测肝组织Fe^(2+)含量;苏木精-伊红染色、油红O染色、电子显微镜观察肝脏组织病理学改变[以NAFLD活动度评分(NAS)作为评价标准];Western blot、RT-qPCR法检测肝脏组织中的Nrf2、Gpx4的蛋白、mRNA表达量。结果与空白组比较,模型组血清ALT、AST、TG、TC、LDL-C、FFA含量,肝组织Fe^(2+)含量,NAS评分,油红O染色面积,细胞及细胞器病理学改变升高(P<0.05)。与模型组比较,中、高剂量组血清ALT、AST、TG、TC、LDL-C、FFA含量及肝组织Fe^(2+)含量降低,肝细胞的各种病理学改变不同程度减轻,高剂量组低于中、低剂量组(P<0.05);HDL-C、SOD升高,Nrf2、Gpx4蛋白及mRNA表达量升高,高剂量组高于中、低剂量组(P<0.05)。结论益气健脾汤可以通过调控Nrf2、Gpx4抑制铁死亡进而改善NAFLD小鼠的肝脏功能、脂肪代谢及肝脏炎症状态。
Objective To explore the mechanism of action of Yiqi Jianpi Decoction on mice with non-alcoholic fatty liver disease(NAFLD).Methods Forty-eight C57BL/6J mice were divided into the blank group,model group,Simvastatin group,and the low-dose,medium-dose,and high-dose groups according to the random number table method,with eight mice in each group.Mice outside the blank group were all given a high-fat diet for NAFLD modeling.After successful modeling,the Simvastatin group was given Simvastatin at a dose of 10 mg/(kg·d)by gavage.The low-dose,medium-dose,and high-dose groups were respectively given 5,10,and 20 g/(kg·d)of Yiqi Jianpi Decoction by gavage,while the blank and model groups were given the same amount of distilled water by gavage.After four weeks of treatment,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglycerides(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),free fatty acids(FFA),and superoxide dismutase(SOD)were detected by enzyme-linked immunosorbent assay.Detection of Fe^(2+)content in liver tissue by colorimetric method;hematoxylin-eosin staining,oil red O staining,and electron microscopy were used to observed liver histopathological changes(the NAFLD activity score[NAS]was used as the evaluation criterion);the protein and mRNA expressions of Nrf2 and Gpx4 in liver tissues were detected by Western blot and RT-qPCR.Results Compared with the blank group,the contents of serum ALT,AST,TG,TC,LDL-C,and FFA,the content of Fe^(2+)in liver tissue,NAS score,the area stained with oil red O,and the pathological changes of cells and organelles in the model group were increased(P<0.05).Compared with the model group,the contents of serum ALT,AST,TG,TC,LDL-C,FFA,and the content of Fe^(2+)in liver tissue in the medium and high-dose groups were decreased,and various pathological changes of hepatocytes were alleviated to varying degrees,the high-dose group was lower than the medium and low-dose groups(P<0.05).The levels of HDL-C and SOD were increased,and the expression levels of Nrf2 and Gpx4 proteins and mRNA were increased,the high-dose group was higher than the medium-dose and low-dose groups(P<0.05).Conclusion Yiqi Jianpi Decoction improves liver function,fat metabolism,and hepatic inflammation in NAFLD mice by modulating Nrf2 and Gpx4 signaling pathways and inhibiting ferroptosis.
作者
李莹
杨磊
袁星星
赵学敏
严贤亮
刘成祥
刘长发
张雅丽
LI Ying;YANG Lei;YUAN Xingxing;ZHAO Xuemin;YAN Xianliang;LIU Chengxiang;LIU Changfa;ZHANG Yali(Heilongjiang Academy of Traditional Chinese Medicine,Heilongjiang Province,Harbin 150036,China;Chengde Medical University,Hebei Province,Chengde 067000,China;Heilongjiang Provincial Hospital for Infectious Disease Prevention and Control,Heilongjiang Province,Harbin 150599,China)
出处
《中国医药导报》
2025年第21期34-41,共8页
China Medical Herald
基金
黑龙江省自然科学基金联合引导项目(LH2023 H078)。
