PDF(Pubmed)
Abstract：
UNASSIGNED: The beneficial effects of fibroblast growth factor 21 (FGF21) and sodium butyrate (NaB) on protection against cholestasis-induced liver fibrosis are not well known. This study aimed to explore the effects of FGF21 and NaB on bile duct ligation (BDL)-induced liver fibrosis.
UNASSIGNED: Wild-type (WT) and FGF21 knockout (KO) mice received BDL surgery for 14 days. Liver fibrosis was assessed by Masson\'s staining for fibrosis marker expressions at the mRNA or protein levels. Adenovirus-mediated FGF21 overexpression in the WT mice was assessed against BDL damage. BDL surgeries were performed in WT and FGF21 KO mice that were administered either phosphate-buffered saline or NaB. The effects of NaB on the energy metabolism and gut microbiota were assessed using stable metabolism detection and 16S rRNA gene sequencing.
UNASSIGNED: BDL-induced liver fibrosis in the WT mice was accompanied by high induction of FGF21. Compared to the WT mice, the FGF21 KO mice showed more severe liver fibrosis induced by BDL. FGF21 overexpression protected against BDL-induced liver fibrosis, as proved by the decreasing α-SMA at both the mRNA and protein levels. NaB administration enhanced the glucose and energy metabolisms as well as remodeled the gut microbiota. NaB alleviated BDL-induced liver fibrosis in the WT mice but aggravated the same in FGF21 KO mice.
UNASSIGNED: FGF21 plays a key role in alleviating cholestasis-induced liver damage and fibrosis. NaB has beneficial effects on cholestasis in an FGF21-dependent manner. NaB administration can thus be a novel nutritional therapy for treating cholestasis via boosting FGF21 signaling and regulating the gut microbiota.
UNASSIGNED: Wild-type (WT) and FGF21 knockout (KO) mice received BDL surgery for 14 days. Liver fibrosis was assessed by Masson\'s staining for fibrosis marker expressions at the mRNA or protein levels. Adenovirus-mediated FGF21 overexpression in the WT mice was assessed against BDL damage. BDL surgeries were performed in WT and FGF21 KO mice that were administered either phosphate-buffered saline or NaB. The effects of NaB on the energy metabolism and gut microbiota were assessed using stable metabolism detection and 16S rRNA gene sequencing.
UNASSIGNED: BDL-induced liver fibrosis in the WT mice was accompanied by high induction of FGF21. Compared to the WT mice, the FGF21 KO mice showed more severe liver fibrosis induced by BDL. FGF21 overexpression protected against BDL-induced liver fibrosis, as proved by the decreasing α-SMA at both the mRNA and protein levels. NaB administration enhanced the glucose and energy metabolisms as well as remodeled the gut microbiota. NaB alleviated BDL-induced liver fibrosis in the WT mice but aggravated the same in FGF21 KO mice.
UNASSIGNED: FGF21 plays a key role in alleviating cholestasis-induced liver damage and fibrosis. NaB has beneficial effects on cholestasis in an FGF21-dependent manner. NaB administration can thus be a novel nutritional therapy for treating cholestasis via boosting FGF21 signaling and regulating the gut microbiota.
摘要：
■成纤维细胞生长因子21（FGF21）和丁酸钠（NaB）对胆汁淤积诱导的肝纤维化的保护作用尚不清楚。本研究旨在探讨FGF21和NaB对胆管结扎（BDL）诱导的肝纤维化的影响。
■野生型(WT)和FGF21敲除(KO)小鼠接受BDL手术14天。通过Masson染色在mRNA或蛋白质水平上的纤维化标志物表达来评估肝纤维化。针对BDL损伤评估WT小鼠中腺病毒介导的FGF21过表达。在施用磷酸盐缓冲盐水或NaB的WT和FGF21KO小鼠中进行BDL手术。使用稳定代谢检测和16SrRNA基因测序评估NaB对能量代谢和肠道微生物群的影响。
■BDL诱导的WT小鼠肝纤维化伴随着FGF21的高诱导。与WT小鼠相比，FGF21KO小鼠表现出BDL诱导的更严重的肝纤维化。FGF21过表达保护BDL诱导的肝纤维化，正如在mRNA和蛋白质水平上α-SMA的降低所证明的那样。NaB给药增强了葡萄糖和能量代谢，并重塑了肠道微生物群。NaB减轻了WT小鼠中BDL诱导的肝纤维化，但在FGF21KO小鼠中加重了这一点。
■FGF21在减轻胆汁淤积引起的肝损伤和纤维化中起关键作用。NaB以FGF21依赖性方式对胆汁淤积具有有益作用。因此,NaB施用可以是用于通过增强FGF21信号传导和调节肠道微生物群治疗胆汁淤积的新型营养疗法。
■野生型(WT)和FGF21敲除(KO)小鼠接受BDL手术14天。通过Masson染色在mRNA或蛋白质水平上的纤维化标志物表达来评估肝纤维化。针对BDL损伤评估WT小鼠中腺病毒介导的FGF21过表达。在施用磷酸盐缓冲盐水或NaB的WT和FGF21KO小鼠中进行BDL手术。使用稳定代谢检测和16SrRNA基因测序评估NaB对能量代谢和肠道微生物群的影响。
■BDL诱导的WT小鼠肝纤维化伴随着FGF21的高诱导。与WT小鼠相比，FGF21KO小鼠表现出BDL诱导的更严重的肝纤维化。FGF21过表达保护BDL诱导的肝纤维化，正如在mRNA和蛋白质水平上α-SMA的降低所证明的那样。NaB给药增强了葡萄糖和能量代谢，并重塑了肠道微生物群。NaB减轻了WT小鼠中BDL诱导的肝纤维化，但在FGF21KO小鼠中加重了这一点。
■FGF21在减轻胆汁淤积引起的肝损伤和纤维化中起关键作用。NaB以FGF21依赖性方式对胆汁淤积具有有益作用。因此,NaB施用可以是用于通过增强FGF21信号传导和调节肠道微生物群治疗胆汁淤积的新型营养疗法。
