摘要
目的探讨复方贞术调脂胶囊(FTZ)对脂多糖(LPS)诱导的急性肝损伤的保护作用及机制。方法将SPF级雄性BALB/c小鼠分为正常(Normal)组、模型(Model)组、FTZ低剂量(FTZ-L)组、FTZ中剂量(FTZ-M)组、FTZ高剂量(FTZ-H)组和阳性对照(Positive control)组,每组8只。Normal组和Model组灌胃给予0.5%CMC-Na,FTZ低、中、高剂量组分别给予0.5、1、2 g·kg^(-1)的FTZ混悬液,Positive control组给予1.3 mg·kg^(-1)的醋酸泼尼松龙。所有动物进行灌胃给药1周后,采用腹腔注射LPS(5 mg·kg^(-1))建立急性肝损伤模型,造模6 h后取血和肝脏标本。采用酶标仪测定血清ALT、AST、TNF-α、IL-1β、IL-6、IL-8、IL-17和内毒素水平;HE法观察肝组织病理学改变;免疫荧光法检测中性粒细胞(Ly-6G+)浸润情况;Western Blot检测TLR4、NF-κB、p-NF-κB、IκB和p-IκB的蛋白表达水平。结果与Model组相比,FTZ干预能够显著降低小鼠ALT、AST、TNF-α、IL-1β、IL-6、IL-8、IL-17和内毒素水平,改善肝静脉出血和炎性细胞浸润,减少Ly-6G+中性粒细胞数量,抑制TLR4、p-NF-κB和p-IκB蛋白的表达。结论FTZ能有效改善LPS诱导的小鼠急性肝损伤,其机制可能与抑制内毒素及TLR4/NF-κB信号通路的激活相关。
Objective To investigate the protective effect and mechanism of Fufang-Zhenzhu-Tiaozhi(FTZ) capsule on lipopolysaccharide(LPS) induced acute liver injury mice.Methods The male BALB/c mice were divided into six groups:Normal group,Model group,FTZ low-dose(FTZ-L) group,FTZ medium-dose(FTZ-M) group,FTZ high-dose(FTZ-H) group,and Positive control group.The Normal and Model groups were intragastrically administered 0.5%CMC-Na.The FTZ-L,FTZ-M and FTZ-H groups were given 0.5,1 and 2 g·kg^(-1) suspension of FTZ,respectively.The Positive control group was given 1.3 mg·kg^(-1) of prednisolone acetate.After continuous intragastric administration of each drug for one week,acute liver injury model was established by single intraperitoneal injection of LPS(5 mg·kg^(-1)).Serum ALT,AST,TNF-α,IL-1β,IL-6,IL-8,IL-17 and endotoxin levels were measured using Microplate Reader.Histopathology of liver was detected by HE.The number of neutrophils(Ly-6G+) was detected by immunofluorescence.The protein expression of TLR4,NF-κB,p-NF-κB,IκB and p-IκB were measured by western blot.Results Compared with the Model group,FTZ significantly decreased ALT,AST,TNF-α,IL-1β,IL-6,IL-8,IL-17 and endotoxin levels,reduced hepatic vein hemorrhage and inflammatory cell infiltration,decreased the numbers of Ly-6 Gpositive neutrophils,and suppressed the expression of TLR4,p-NF-κB and p-IκB protein.Conclusion FTZ can effectively ameliorate LPS-induced acute liver injury in mice,the mechanism may be associated with the inhibition of the endotoxin and TLR4/NF-κB signaling pathway.
作者
林子扬
林泉酉
刁礼聪
陈洁雯
陈耿娜
杨祎琦
贝伟剑
郭姣
Lin Ziyang;Lin Quanyou;Diao Licong;Chen Jiewen;Chen Gengna;Yang Yiqi;Bei Wejian;Guo Jiao(Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine,Guangdong Pharmaceutical University,Guangzhou 510006,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2023年第1期430-437,共8页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
广东药科大学人才项目(51377010):科研启动费,负责人:杨祎琦。
