Department of Pediatric Surgery, Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan.
Department of Pediatric Surgery, Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area, Research and Education Assembly, Kagoshima University, Kagoshima, Japan; Clinical Training Center, Kagoshima University Hospital, Kagoshima, Japan.
J Pediatr Surg. 2022 Jul;57(7):1286-1292. doi: 10.1016/j.jpedsurg.2022.02.030. Epub 2022 Mar 13.
Short bowel syndrome (SBS) patients require total parenteral nutrition (TPN) following massive small bowel resection (SBR), which may cause intestinal failure-associated liver disease (IFALD), a life-threatening complication. Hepatocyte growth factor (HGF) acts as a potent hepatocyte mitogen with anti inflammatory and antioxidant actions. The present study evaluated the effect of recombinant human HGF (rh-HGF) on SBR and subsequent IFALD using a parentally fed rat model of SBS.
Rats underwent jugular vein catheterization for continuous TPN and 90% SBR. They were divided into 2 groups: TPN alone (SBS/TPN group: n = 7) or TPN plus the intravenous administration of rh-HGF (0.3 mg/kg/day) (SBS/TPN+HGF group: n = 7). On day 7, their tissues and stool were harvested to evaluate the effects of HGF.
Regarding the histological findings, based on the nonalcoholic fatty liver disease (NAFLD) activity score, the SBS/TPN+HGF group showed significantly less hepatic steatosis and inflammatory cell infiltration than the SBS/TPN group (NAFLD activity score, 4.00 ± 1.83 vs. 1.00 ± 0.82; p < 0.01). The SBS/TPN+HGF group showed a higher expression of Farnesoid X receptor in the liver and lower expression of Toll-like receptor 4 in the ileum than the SBS/TPN group. Regarding the composition of the bacterial gut microbiota, Actinobacteria, Bacteroidetes and Proteobacteria were decreased in the SBS/TPN+HGF group compared with the SBS/TPN group.
In our SBS with TPN rat model, rh-HGF administration had a preventive effect against hepatic steatosis and dysbiosis. rh-HGF may therefore be a potentially effective therapeutic agent for SBS and subsequent IFALD.
Experimental research.
大量小肠切除（SBR）后，短肠综合征（SBS）患者需要全胃肠外营养（TPN），这可能导致危及生命的并发症——肠衰竭相关肝病（IFALD）。肝细胞生长因子（HGF）作为一种有效的肝细胞有丝分裂原，具有抗炎和抗氧化作用。本研究采用肠外喂养的 SBS 大鼠模型，评估重组人 HGF（rh-HGF）对 SBR 及随后 IFALD 的影响。
大鼠行颈静脉置管行持续 TPN 及 90%SBR。将其分为 2 组：仅 TPN（SBS/TPN 组：n=7）或 TPN 加静脉注射 rh-HGF（0.3mg/kg/天）（SBS/TPN+HGF 组：n=7）。第 7 天，取其组织和粪便进行评估。
在组织学发现方面，根据非酒精性脂肪性肝病（NAFLD）活动评分，SBS/TPN+HGF 组肝脂肪变性和炎症细胞浸润程度明显低于 SBS/TPN 组（NAFLD 活动评分：4.00±1.83 比 1.00±0.82；p<0.01）。SBS/TPN+HGF 组肝法尼醇 X 受体表达较高，回肠 Toll 样受体 4 表达较低。在肠道菌群组成方面，与 SBS/TPN 组相比，SBS/TPN+HGF 组放线菌门、拟杆菌门和变形菌门减少。
在我们的 TPN 致 SBS 大鼠模型中，rh-HGF 给药对肝脂肪变性和肠道菌群失调具有预防作用。rh-HGF 可能是治疗 SBS 和随后 IFALD 的潜在有效治疗剂。
实验研究。
