Page 23 - 南京医科大学学报自然科学版

第41卷第9期 南京医科大学学报（自然科学版）
2021年9月 Journal of Nanjing Medical University（Natural Sciences） ·1289 ·

·基础研究·

活性维生素D3对脓毒血症小鼠急性肝损伤的保护作用及机制

弓玉祥 ，倪维杰 ，倪海锋 ，张思宇 ，杨旻宇 ，陈平圣 1，2*
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东南大学附属中大医院肾脏病研究所，江苏 南京 210009；东南大学医学院，江苏 南京 210009
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［摘 要］ 目的：探讨活性维生素D3（vitamin D3，Vit D3）对内毒素（lipopolysaccharide，LPS）诱导小鼠急性肝损伤的保护作用
及机制。方法：将 40 只雄性 C57BL/6 小鼠随机分成 4 组：对照组、Vit D3 组、模型组（LPS 组）和治疗组（LPS+ Vit D3 组），每组
10 只。模型组和治疗组给予15 mg/kg LPS腹腔注射建立脓毒血症小鼠急性肝损伤模型。Vit D3组和治疗组小鼠在注射LPS后
即刻（0 h）、8 h、16 h，给予Vit D3（2.5 μg/kg）灌胃，对照组和模型组给予等体积生理盐水灌胃。24 h后水合氯醛麻醉处死小鼠，
收集小鼠的血液和肝脏用于后续实验。结果：与模型组比较，Vit D3可降低血清和肝脏丙氨酸氨基转移酶（alanine aminotrans⁃
ferase，ALT）和天门冬氨酸氨基转移酶（aspartate aminotransferase，AST）水平，提高肝组织抗氧化酶活性，减轻肝脏病理改变。
与模型组相比，Vit D3降低了血清中肿瘤坏死因子α（tumor necrosis factor⁃α，TNF⁃α）和白细胞介素⁃1（interleukin⁃1，IL⁃1）的水
平。此外，与模型组相比，Vit D3下调了肝组织中IL⁃1β、TNF⁃α、NF⁃κB p65 和 NF⁃κB p50的表达，上调了肝组织中核因子E2相
关因子2（nuclear factor⁃erythroid 2p45⁃relatec factor 2，Nrf2）、血红素加氧酶⁃1（heme oxygenase⁃1，HO⁃1）和维生素D受体（vitamin
D receptor，VDR）的表达。结论：Vit D3对LPS诱导的小鼠急性肝损伤具有保护作用，这一效果可能部分是VDR通路抑制氧化
应激和炎症所致。
［关键词］ 急性肝损伤；炎症；氧化应激；活性维生素D3
［中图分类号］ R631 ［文献标志码］ A ［文章编号］ 1007⁃4368（2021）09⁃1289⁃08
doi：10.7655/NYDXBNS20210903

Protective effects and mechanism of vitamin D3 against lipopolysaccharide⁃induced acute
liver injury in mice

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GONG Yuxiang ，NI Weijie ，NI Haifeng ，ZHANG Siyu ，YANG Mingyu ，CHEN Pingsheng
1 Institute of Nephrology，Zhong Da Hospital Affiliated to Southeast University，Nanjing 210009；School of Medicine，
2
Southeast University，Nanjing 210009，China

［Abstract］ Objective：The aim of the present study was to investigate the protective effects and mechanisms of of vitamin D3（Vit
D3）on lipopolysaccharide（LPS）⁃induced liver injury in mice. Methods：Forty C57BL/6 mice were randomly assigned to 4 groups（n=
10）as follows：control group，vitamin D3 group（Vit D3），model group（LPS），and treatment group（LPS+Vit D3）. Acute liver injury of
mice in model group and treatment group was induced by the intraperitoneal injection of 15 mg/kg LPS. Mice in Vit D3 group and
treatment group were given 2.5 μg/kg vitamin D3 at the time points of 0 h，8 h，16 h after LPS injection，while mice in the control and
model groups were treated with an equivalent volume of 0.9% sodium chloride solution. After 24 h，all mice were anesthetized with
chloral hydrate. Blood and livers of mice were collected for subsequent experiments. Results：Vitamin D3 decreased the levels of
alanine aminotransferase（ALT）and aspartate aminotransferase（AST）in serum，increased the activity of antioxidant enzymes in the
liver tissues compared with those in the model group and attenuated liver pathologic changes. In addition，vitamin D3 downregulated
the serum levels of tumor necrosis factor⁃α（TNF⁃α），interleukin ⁃1β（IL⁃1β）compared with those in the model group. Meanwhile，
vitamin D3 downregulated the protein expression of IL⁃1β，TNF⁃α，NF⁃κB p65 and NF⁃κB p50，upregulated the expression of nuclear
factor⁃erythroid 2p45⁃related factor 2（Nrf2），heme oxygenase⁃1（HO⁃1）and vitamin D receptor（VDR）in liver tissues compared with
those in the model group. Conclusion：Vitamin D3 showed a protective effect against LPS⁃induced acute liver injury in mice，which
may be partly due to the inhibition of oxidative stress and inflammation via the VDR pathway.
［Key words］ acute liver injury；inflammation；oxidative stress；vitamin D3
［J Nanjing Med Univ，2021，41（09）：1289⁃1295，1321］

［基金项目］ 江苏省重点研发计划（BE2019712）
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通信作者（Corresponding author），E⁃mail：chenps@seu.edu.cn