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Abstract Title:Therapeutic potential of berberine in attenuating cholestatic liver injury: insights from a PSC鼠标模型。
摘要来源:
细胞Biosci。 2024年1月25日; 14(1):14。 EPUB 2024 JAN25。PMID: 38273376 38273376 Su, Yun-Ling Tai, Grayson W Way, Jing Zeng, Qianhua Yan, Ying Xu, Xuan Wang, Emily C Gurley, Xi-Qiao Zhou, Jinze Liu, Jinpeng Liu, Weidong Chen, Phillip B Hylemon, Huiping Zhou
Article Affiliation:Yanyan Wang
Abstract:
背景和目标: 主要的硬化性胆管炎(PSC)是一种慢性肝病,其特征是进行性胆汁炎症和胆管损伤。 berberine(bbr)是生物activE异喹啉生物碱在各种草药中发现,对包括肝脏疾病在内的代谢和炎症性疾病具有多种有益作用。 This study aimed to examine the therapeutic effect of BBR on cholestatic liver injury in a PSC mouse model (Mdr2mice) and elucidate the underlying mechanisms.
METHODS: Mdr2mice (12-14 weeks old, both sexes) received either BBR (50 mg/kg) or control solution daily for八周通过口腔烤。组织学和血清生化分析用于评估纤维化肝损伤严重程度。总RNASEQ和途径分析用于确定BBR在肝脏中调节的潜在信号通路。通过QRT-PCR或Western印迹分析验证了调节肝纤维化,胆管增殖,炎症和胆汁酸代谢的关键基因的表达水平。血清,肝脏,小肠和粪便中的胆汁酸组成和水平通过LC-MS/MS测量BBR的D组织分布。通过基因表达分析和组织学分析评估肠道炎症和损伤。 The impact on the gut microbiome was assessed using 16S rRNA gene sequencing.
RESULTS: BBR treatment significantly ameliorated cholestatic liver injury, evidenced by decreased serum levels of AST, ALT, and ALP, and reduced bile duct proliferation and hepatic fibrosis, as shown by H&E,Picro-Sirius Red和CK19 IHC染色。 RNASEQ和QRT-PCR分析表明,纤维化和炎症基因表达有很大的抑制作用。 BBR还通过下调CHOP,ATF4和XBP-1表达来减轻ER应力。此外,BBR通过改变肝脏和小肠中的关键基因表达来调节胆汁酸代谢,从而导致恢复的胆汁酸稳态,其特征是血清,肝脏和小肠中的总胆汁酸降低,并增加了粪便排泄。离子。此外,BBR通过调节肠道菌群。
结论: