Subcutaneous Inoculation of Echinococcus multilocularis Induces Delayed Regeneration after Partial Hepatectomy
Subcutaneous Inoculation of Echinococcus multilocularis Induces Delayed Regeneration after Partial Hepatectomy
复制标题
皮下接种多房棘球绦虫可诱导部分肝切除术后再生延迟。
DOI：
10.1038/s41598-018-37293-0
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发表时间：
2019-01-24
影响因子：
4.6
通讯作者：
Wen, Hao
中科院分区：
文献类型：
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作者：
Apaer, Shadike;Tuxun, Tuerhongjiang;Wen, Hao
泡状棘球蚴病（AE）是由多房棘球蚴（E.多房性），肝切除术是肝脏AE患者的主要方式。部分肝切除术（PHx）后的肝再生在这些患者中具有挑战性，需要进一步研究。到目前为止，有关E.多房性对PHx后肝再生的影响有限。本文建立了大肠杆菌皮下感染模型。在C57 BL/6小鼠中发展多房性，并且在3个月后，进行PHx。在指定的PHx后时间点（0、24、48、96和168 h），在吸入异氟烷（2%）麻醉下采集血浆和肝脏样品。参数包括未来残肝/体重比（FLR/BW）、肝功能检查（AST和ALT）和相关细胞因子（TNF-α、IL-6、因子V、HMGB 1、TGF-β、TSP-1和TLR 4）和蛋白质（MyD 88和STAT 3）。为了评估肝细胞的增殖强度，在再生肝组织中进行BrdU、Ki 67和PAS染色。感染组FLR/BW从术后48 h开始低于对照组。对照组BrdU阳性肝细胞比例在48 h达到高峰，感染组在96 h达到高峰，然后逐渐下降。在手术后的前48小时内，感染组的AST和ALT水平均较低;然而，这些水平从手术后96小时开始改变。在感染组中，前炎症细胞因子TNF-α和IL-6的浓度和mRNA表达水平表现出延迟的峰值。此外，术后，TGF-β和TSP-1水平在感染组中在每个不同的时间点与对照组中的那些相比显示出高水平;然而，在对照组中在96 h观察到高水平的TGF-β。术后96 h，感染组MyD 88和STAT 3蛋白表达水平明显高于对照组。C57 BL/6小鼠皮下感染E.在目前的研究中，这一现象可能与慢性大肠杆菌引起的免疫耐受环境中促炎细胞因子的改变有关。多房性感染
Alveolar echinococcosis (AE) is caused by the larval stage of echinococcus multilocularis (E. multilocularis), and hepatectomy is the main modality in hepatic AE patients. Liver regeneration after partial hepatectomy (PHx) in such patients is challenging, and further investigation is needed. Thus far, knowledge regarding the possible impact of E. multilocularis on liver regeneration after PHx is limited. Herein, a subcutaneous infection model of E. multilocularis was developed in C57 BL/6 mice, and after 3 months, PHx was performed. Plasma and liver samples were harvested under inhalational isofluorane (2%) anaesthesia at designated post-PHx time points (0, 24, 48, 96 and 168 h). The parameters included the future remnant liver/body weight ratio (FLR/BW), liver function tests (AST and ALT) and related cytokines (TNF-alpha, IL-6, Factor V, HMGB1, TGF-beta, TSP-1, and TLR4) and proteins (MyD88 and STAT3). To assess the proliferation intensity of hepatocytes, BrdU, Ki67 and PAS staining were carried out in regenerated liver tissue. The FLR/BW in the infected group from 48 h after surgery was lower than that in the control group. The BrdU positive hepatocyte proportions reached their peak at 48 h in the control group and 96 h in the infected group and then gradually decreased. During the first 48 h after surgery, both the AST and ALT levels in the infected group were lower; however, these levels were altered from 96 h after surgery. In the infected group, the concentrations and mRNA expression levels of the pre-inflammatory cytokines TNF-alpha and IL-6 demonstrated a delayed peak. Moreover, post-operatively, the TGF-beta and TSP-1 levels showed high levels in the infected group at each different time-point compared to those in the control group; however, high levels of TGF-beta were observed at 96 h in the control group. The MyD88 and STAT3 protein expression levels in the infected group were markedly higher than those in the control group 96 h after surgery. Delayed liver regeneration after PHx was observed in the C57 BL/6 mice with the subcutaneous infection of E. multilocularis in the current study. This phenomenon could be partially explained by the alteration in the pro-inflammatory cytokines in the immunotolerant milieu induced by chronic E. multilocularis infection.