The influence of dietary restriction on hepatic mononuclear cell numbers and functions in mice
The influence of dietary restriction on hepatic mononuclear cell numbers and functions in mice
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饮食限制对小鼠肝单个核细胞数量和功能的影响
DOI：
10.1016/j.jss.2015.05.061
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发表时间：
2015
期刊：
影响因子：
2.2
通讯作者：
Yamamoto J
中科院分区：
文献类型：
--
作者：
Moriya T;Fukatsu K;Iwaya K;Noguchi M;Saitoh D;Miyazaki M;Hase K;Yamamoto J
背景患有胃肠道恶性肿瘤的外科患者营养不良的风险增加。然而，饮食限制（DR）（营养不良的一种形式）损害肝脏免疫力的机制仍有待阐明。本研究旨在探讨 DR 对小鼠脂多糖 (LPS) 反应对肝单核细胞 (MNC) 数量、亚群和细胞因子产生（肿瘤坏死因子 α [TNF-α]、干扰素 γ [IFN-γ] 和白细胞介素 10 [IL-10]）的影响。还评估了胆囊中的免疫球蛋白（Ig）A水平和肝脏中的组织病理学变化。 材料和方法将雄性癌症研究所小鼠随机分配到三个饮食组：随意饮食（AD）、轻度限制（MR）和严重限制（SR）。 AD、MR 和 SR 组每天分别接受 190、133 和 76 g/kg 的小鼠饲料，持续 7 天。喂养小鼠 7 天后，分离肝脏 MNC。对肝脏 MNC 总数进行计数，并通过流式细胞术确定亚群。测量了肝脏 MNC 对 LPS 的反应产生的细胞因子（TNF-α、IFN-γ 和 IL-10）。分析血样的肝胆生化参数。采用酶联免疫吸附测定法测量胆囊胆汁中的 IgA 水平。此外，还进行了肝脏组织学检查。结果MR和SR组的肝脏MNC数量显着低于AD组，而MR和SR组之间无显着差异。 SR组的B细胞百分比显着低于MR和AD组，而SR组的T细胞百分比高于MR和AD组。 SR组库普弗细胞百分比显着低于AD组，而MR组则介于SR组和AD组之间。在 AD 组中，肝 MNC 培养物上清液中的 TNF-α 和 IL-10 水平随 LPS 剂量依赖性增加。然而，MR 组的增加幅度很小，而 SR 组则没有增加。 SR和MR组胆囊胆汁中的IgA水平显着低于AD组。肝切片苏木精和伊红染色显示，SR组肝脏出现肝细胞萎缩和肝窦扩张，而AD组则没有这些变化。 结论 DR随着亚群变化而减少肝脏MNC数量，降低胆囊胆汁中IgA水平，减弱肝脏MNC产生细胞因子，并诱发肝脏病理损伤，这可能是宿主防御受损的重要机制与营养不良有关。
BackgroundSurgical patients with gastrointestinal malignancies are at increased risk for malnutrition. However, the mechanism by which dietary restriction (DR), one form of malnutrition, impairs hepatic immunity remains to be clarified. The present study was designed to examine the influence of DR on hepatic mononuclear cell (MNC) numbers, subpopulations, and cytokine productions (tumor necrosis factor α [TNF-α], interferon gamma [IFN-γ], and interleukin 10 [IL-10]) in response to lipopolysaccharide (LPS) in mice. Immunoglobulin (Ig) A levels in the gallbladder and histopathologic changes in the liver were also assessed.Material and methodsMale Institute of Cancer Research mice were randomly assigned to three dietary groups:ad libitum(AD), mild restriction (MR), and severe restriction (SR). The AD, MR, and SR groups received daily mouse chow in amounts of 190, 133, and 76 g/kg, respectively, for 7 d. After the mice had been fed for 7 d, hepatic MNCs were isolated. Total hepatic MNCs were counted and subpopulations were determined by flow cytometry. Cytokine productions (TNF-α, IFN-γ, and IL-10) by hepatic MNCs in response to LPS were measured. Blood samples were analyzed for hepatobiliary biochemical parameters. IgA levels in gallbladder bile were measured with enzyme-linked immunosorbent assay. In addition, liver histologies were examined.ResultsHepatic MNC numbers were significantly lower in the MR and SR groups than in the AD group, with no significant difference between the MR and SR groups. The percentage of B cells was significantly lower in the SR group than in the MR and AD groups, whereas the T-cell percentage was higher in the SR group than in the MR and AD groups. The percentage of Kupffer cells was significantly lower in the SR group than in the AD group, whereas that in the MR group was midway between those in the SR and AD groups. TNF-α and IL-10 levels in hepatic MNC culture supernatants were increased LPS-dose dependently in the AD group. However, the increase was slight in the MR group and absent in the SR group. The IgA levels in gallbladder bile were significantly lower in the SR and MR groups than in the AD group. On the basis of hematoxylin and eosin staining of hepatic sections, livers from the SR group showed atrophic hepatocytes and sinusoidal dilatation, whereas these changes were absent in the AD group.ConclusionsDR decreases hepatic MNC number with subpopulation changes, reduces IgA levels in gallbladder bile, blunts cytokine production by hepatic MNCs, and induces pathologic damage in the liver, which may be an important mechanism underlying the impaired host defense associated with malnutrition.