基于TLR4信号通路探寻枳椇饮防治急性酒精性肝损伤的作用机制  

Exploring the Mechanism of Zhiju Decoction in Preventing and Treating Acute Alcoholic Liver Injury Based on the TLR4 Signaling Pathway

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作  者:韩辰辰 李勇坤 邱雪梅 王娅琴 朱达 罗庆文 何飘燕 王振安 赵淳 吴英 叶勇 Han Chenchen;Li Yongkun;Qiu Xuemei;Wang Yaqin;Zhu Da;Luo Qingwen;He Piaoyan;Wang Zhen′an;Zhao Chun;Wu Ying;Ye Yong(The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine,Yunnan,Kunming 650000,China)

机构地区:[1]云南中医药大学第一附属医院,云南昆明650000

出  处:《中国中医急症》2025年第2期200-203,210,共5页Journal of Emergency in Traditional Chinese Medicine

基  金:全国第七批名老中医药专家学术经验继承工作项目(国中医药人教函[2022]76号);云南省沈宝藩专家工作站(202005AF150031);云南省教育厅科学研究基金项目(2022Y538)。

摘  要:目的 基于TLR4信号通路探寻枳椇饮治疗急性酒精性肝损伤的作用机制。方法 将昆明种雄性小鼠随机分为空白组、模型组、阳性药物组(联苯双酯滴丸)、枳椇饮高剂量组、枳椇饮中剂量组和枳椇饮低剂量组,采用56°红星二锅头白酒灌胃1 d建立急性酒精性肝损伤模型,并灌胃相应药物防治。末次给药后,禁食不禁水16 h处死小鼠摘眼球取血,分析血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)活性和甘油三酯(TG)、总胆固醇(TC)含量,ELISA检测肝组织中的炎症因子肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)的含量变化,取肝组织切片HE染色进行病理学分析。Westem btottingg法测定肝脏组织中MyD88、TLR4、核转录因子-κB(NF-κB)的蛋白表达水平。结果 模型组小鼠的血清ALT、AST、TG、TC及炎症因子水平均较空白组升高(P <0.05),肝组织经HE染色后出现细胞水肿等表现,提示模型组小鼠发生肝损伤。WB分析,与空白相比,模型组TLR-4、MyD88的蛋白相对表达量升高,NF-κB蛋白相对表达量下降。各用药组与模型组相比,阳性药物组TLR-4、MyD88的蛋白相对表达量升高,NF-κB蛋白相对表达量下降;枳椇饮高、中剂量组TLR-4、MyD88、NF-κB的蛋白相对表达量均有不同程度下降;低剂量组TLR-4、NF-κB蛋白相对表达量升高,MyD88蛋白相对表达量下降(均P> 0.05)。结论 枳椇饮可以改善急性酒精性肝损伤小鼠的炎症因子水平,对急性酒精性肝损伤有一定的保护作用,其机制可能与TLR4信号通路的激活有关。Objective:To explore the mechanism of Zhiju Decoction in treating acute alcoholic liver injury based on the TLR4 signaling pathway.Methods:Kunming strain male mice were randomly divided into a blank group,a model group,a positive drug group(biphenyl dicarboxylate pills),high-dose Zhiju Decoction group,medi-um-dose Zhiju Decoction group,and low-dose Zhiju Decoction group.An acute alcoholic liver injury model was es-tablished by intragastric administration of 56°Hongxing Erguotou liquor for 1 day,followed by corresponding drug treatments.After the last administration,mice were fasted but not water-deprived for 16 hours before being sacri-ficed to collect blood samples for analysis of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST)activity,and triglyceride(TG),total cholesterol(TC)content.ELISA was used to detect changes in inflam-matory factors TNF-α,IL-6,and IL-1βin liver tissues.Liver tissue sections were stained with HE for pathologi-cal analysis.Western blting was used to measure protein expression levels of MyD88,TLR4,NF-kB in liver tis-sues,Results:Compared with the blank group,the model group showed increased serum ALT,AST,TG,TC lev-els,and inflammatory factor levels(P<0.05).HE staining revealed cellular edema in the model group's liver tis-sues,indicating liver injury.Western blotting analysis showed that compared with the blank group,the model group had higher relative protein expression of TLR4 and MyD88 but lower NF-kB expression.Compared with the model group,the positive drug group showed higher relative protein expression of TLR4 and MyD88 but lower NF-kB expression;the high and medium dose groups of Zhiju Decoction showed varying degrees of reduction in the rel-ative expression of TLR4,MyD88,and NF-kB proteins;the low dose group showed increased relative expression of TLR4 and NF-kB proteins but decreased MyD88 expression(all P>0.05).Conclusion:Zhiju Decoction can im-prove inflammatory factor levels in mice with acute alcoholic liver injury and provide some protective effects ag

关 键 词:急性酒精性肝损伤 枳椇饮 TLR4信号通路 小鼠 

分 类 号:R285.5[医药卫生—中药学]

 

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