基于TLR4/MyD88/NF-κB信号通路探讨滋水涵木法治疗抗结核药物性肝损伤大鼠的作用机制  

Discussion on the mechanism of Zishui Hanmu Recipe in anti-tuberculosis drug-induced liver injury rats based on TLR4/MyD88/NF-κB signaling pathway

作　　者：高悦 江锋[1] 苏新 薛婧 杜可心 冯建美 史曼玉 GAO Yue;JIANG Feng;SU Xin;XUE Jing;DU Kexin;FENG Jianmei;SHI Manyu(Department of Gastroenterology,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing100700,China;Department of Gastroenterology,Yanqing Hospital of Beijing Chinese Medicine Hospital,Beijing100700,China)

机构地区：[1]北京中医药大学东直门医院消化科,北京100700 [2]北京中医医院延庆医院消化科,北京100700

出　　处：《中国医药导报》2025年第7期8-14,共7页China Medical Herald

基　　金：北京中医药大学东直门医院科技创新专项项目(DZMKJCX-2023-015)。

摘　　要：目的 基于TLR4/My D88/NF-κB信号通路探讨滋水涵木法治疗抗结核药物性肝损伤(ATB-DILI)大鼠的作用机制。方法 选取52只雄性SPF级体重为120~150 g的Wistar大鼠,适应性喂养7 d后,按照随机数字表法分为空白对照组(14只)、造模组(38只)。空白对照组给予0.5%羧甲基纤维素钠(CMC-Na)灌胃,造模组给予异烟肼(100 mg/kg)+利福平(400 mg/kg)+0.5%CMC-Na灌胃,1次/d,灌胃4周后,两组各取材6只大鼠,以造模组血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)指标高于空白对照组(P<0.05),且肝小叶结构被破坏作为造模成功的判定标准。造模成功后,造模组剩余32只大鼠按照随机数字表法分成中药低剂量组、中药高剂量组、双环醇组及模型对照组,每组各8只。中药低、中药高剂量组分别给予8.19、16.38 g/kg滋水涵木法中药灌胃,双环醇组给予双环醇片200 mg/kg灌胃,空白对照组(8只)和模型对照组给予等体积生理盐水+0.5%CMC-Na灌胃,1次/d,灌胃3周。生化法检测各组大鼠血清ALT、AST、总胆红素(TBil)、碱性磷酸酶(ALP)水平,酶联免疫吸附试验法检测肝组织肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)及血清脂多糖(LPS)水平,HE染色观察肝组织病理学改变,PCR法检测大鼠肝组织TLR4、My D88及NF-κB的m RNA表达水平。结果 与空白对照组比较,模型对照组ALT、AST、ALP及TBil水平升高(P<0.01);与模型对照组比较,中药低、高剂量组ALT、AST、ALP及TBil水平下降(P<0.05);HE染色发现,模型对照组可见肝细胞排列疏松,空泡样变,少量肝细胞坏死伴炎症细胞浸润。与模型对照组比较,中药低剂量组仅见肝细胞空泡样变,少量炎症细胞浸润;中药高剂量组仅见炎症细胞浸润,且炎症细胞较中药低剂量组少;与空白对照组比较,模型对照组IL-6、TNF-α及LPS水平升高(P<0.01);与模型对照组比较,中药低、高剂量组IL-6、TNF-α及LPS水平降低(P<0.05);与中药低剂量�Objective To investigate the mechanism of the treatment of anti-tuberculosis drug-induced liver injury(ATB-DILI)in rats with Zishui Hanmu recipe based on TLR4/MyD88/NF-κB signaling pathway.Methods After seven days of adaptive feeding,fifty-two male Wistar rats with SPF grade body weight of 120-150 g were divided into blank control group(14 rats)and modeling group(38 rats)according to random number table method.The blank control group was given 0.5%sodium carboxymethyl cellulose(CMC-Na),while the modeling group was given Isoniazid(100 mg/kg)+Rifampicin(400 mg/kg)+0.5%CMC-Na by intragastric administration,once a day,after four weeks of intragastric administration,six rats in each group were collected.The serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)indexes in the modeling group were higher than those in the control group(P<0.05),and the failure of the liver lobular structure was taken as the criterion for the success of modeling.After successful modeling, the remaining 32 rats in the modeling group were divided into low-dose Chinese medicine group, high-dose Chinese medicine group, bicyclic alcohol group, and model control group according to random number table, with eight rats in each group. The low-dose and high-dose Chinese medicine groups were given 8.19 g/kg and 16.38 g/kg traditional Chinese medicine by Zizhu Hanmu Recipe, respectively;the Dicycloalcohol group was given 200 mg/kg Dicycloalcohol Tablets by intragastric administration;the blank control group (eight rats) and the model control group were given equal volume normal saline +0.5% CMC-Na by intragastric administration, once a day, for three weeks. Serum ALT, AST, total bilirubin (TBil), and alkaline phosphatase (ALP) levels were detected by biochemical method, liver tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and serum lipopolysaccharide (LPS) levels were detected by enzyme linked immunosorbent assay method, and HE staining was used to observe liver histopathological changes. The mRNA expression levels of TLR4,

关 键 词：抗结核药物性肝损伤 滋水涵木 TLR4/MyD88/NF-κB信号通路 作用机制 

分 类 号：R285.5[医药卫生—中药学] R575[医药卫生—中医学]