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基于抑制TLR4/NF-κB/NLRP3炎症通路探讨芍药苷与姜黄素混悬液对急性肝损伤的保护作用

Investigating Protective Effect of Suspension of Paeoniflorin in Combination with Curcumin Against Acute Liver Injury Based on Inhibition of TLR4/NF-κB/NLRP3 Inflammatory Pathway.

作者信息

Wu Zhengkun, Zhao Yinquan, Wang Yang, Li Haohuan, Xu Funeng, Zhang Wei, Fu Hualin, Yin Lizi, Amevor Felix Kwame, Lin Juchun, Li Danqin, Shu Gang

机构信息

Department of Basic Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.

College of Veterinary Medicine, Kansas State University, 1700 Denison Ave, Manhattan, KS 66502, USA.

出版信息

Int J Mol Sci. 2025 Jun 30;26(13):6324. doi: 10.3390/ijms26136324.

Abstract

The objective of this study was to formulate a compound suspension comprising paeoniflorin and curcumin, assess its quality characteristics, and investigate its protective efficacy against acute liver injury in mice. The prescriptions were screened using a single-factor test, and nine groups of suspensions were prepared using the dispersion method. Fifty KM mice (four weeks old) were selected and randomly divided into five groups: the CON, LD, PF, CUR, and PC groups. The doses of both paeoniflorin and curcumin were 100 mg/kg BW, and different suspensions were given to different groups by gavage for 14 days. All the groups except the CON group were injected intraperitoneally with 20 μg/kg LPS and 700 mg/kg D-GalN on the last day. According to the results, the suspension prepared using the optimal prescriptions was orange-yellow in color, with homogeneous turbidity and good re-dispersibility. The combination treatment could reduce the severity of pathological injuries of liver, improve the ultrastructure of hepatocytes, increase the activities of T-SOD, GSH-Px, and CAT, decrease the levels of IFN-γ, TNF-α, and IL-1, and down-regulate the expression of genes such as TLR4, MyD88, IκBα, and NLRP3. The underlying mechanism might be associated with the enhancement of antioxidant enzyme activities, inhibition of the TLR4/NF-κB/NLRP3 signaling pathway, and suppression of inflammasome assembly and release in hepatic tissues.

摘要

本研究的目的是制备一种包含芍药苷和姜黄素的复合混悬液,评估其质量特性,并研究其对小鼠急性肝损伤的保护作用。采用单因素试验筛选处方,用分散法制备9组混悬液。选取50只4周龄的KM小鼠,随机分为5组:对照组(CON)、低剂量组(LD)、芍药苷组(PF)、姜黄素组(CUR)和芍药苷-姜黄素组(PC)。芍药苷和姜黄素的剂量均为100 mg/kg体重,不同组通过灌胃给予不同的混悬液,持续14天。除对照组外,所有组在最后一天腹腔注射20 μg/kg脂多糖(LPS)和700 mg/kg D-半乳糖胺(D-GalN)。结果显示,采用最优处方制备的混悬液呈橙黄色,浊度均匀,再分散性良好。联合治疗可减轻肝脏病理损伤的严重程度,改善肝细胞超微结构,提高总超氧化物歧化酶(T-SOD)、谷胱甘肽过氧化物酶(GSH-Px)和过氧化氢酶(CAT)的活性,降低干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)和白细胞介素-1(IL-1)的水平,并下调Toll样受体4(TLR4)、髓样分化因子88(MyD88)、核因子κB抑制蛋白α(IκBα)和NOD样受体蛋白3(NLRP3)等基因的表达。其潜在机制可能与增强抗氧化酶活性、抑制TLR4/核因子κB(NF-κB)/NLRP3信号通路以及抑制肝组织中炎性小体的组装和释放有关。

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