Page 35 - 南京医科大学自然科学版第1期

第41卷第1期 南京医科大学学报（自然科学版）
2021年1月 Journal of Nanjing Medical University（Natural Sciences） · 29 ·

·基础研究·

Urantide对动脉粥样硬化大鼠脂肪肝组织中STAT3磷酸化的影响

崔海鹏 ，林映雪 ，王怡宁 ，王 途 ，李 英 ，赵 娟 1*
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承德医学院病理生理学教研室，河北 承德 067000；承德医学院附属医院药学部，河北 承德 067000
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［摘 要］ 目的：探讨尾加压素Ⅱ受体拮抗剂Urantide 对动脉粥样硬化（atherosclerosis，AS）大鼠脂肪肝组织中信号转导与转
录激活因子 3（signal transducer and activator of transcription 3，STAT3）表达的影响。方法：30 只雄性 Wistar 大鼠随机分为正常
组、AS组、Urantide组。AS组和Urantide组均给予腹腔注射维生素D3 （vitamin D3，VD3 ）150 μg/（kg·d）连续3 d，并饲喂高脂饲料
诱导AS，Urantide 组在造模成功后给予尾静脉注射Urantide 30 μg/（kg·d）连续2周。测量各组大鼠体重及肝重，计算肝系数；
HE染色观察大鼠胸主动脉、肝的形态学改变；生化检测大鼠血清中丙氨酸氨基转移酶（alanine aminotransferase，ALT）、天门冬
氨酸氨基转移酶（aspartate aminotransferase，AST）的含量。RT⁃qPCR方法检测肝脏STAT3 mRNA表达水平；免疫印迹检测肝脏
STAT3、p⁃STAT3蛋白水平；免疫荧光法检测肝细胞中p⁃STAT3水平。结果：与正常组相比，AS组大鼠胸主动脉出现典型的AS
病理学改变，肝出现典型的脂肪变性，AS组大鼠肝系数、血清ALT、AST含量以及肝p⁃STAT3的蛋白水平显著升高。与AS组相
比，Urantide组大鼠AS病变和肝脂肪变性明显减轻；大鼠肝系数、血清ALT、AST含量以及肝p⁃STAT3水平显著降低。各组大
鼠肝中STAT3的mRNA及蛋白表达水平无显著变化。结论：Urantide可通过抑制STAT3的活化缓解肝损伤，治疗脂肪肝。
［关键词］ Urantide；动脉粥样硬化；脂肪肝；STAT3；大鼠
［中图分类号］ R575.5 ［文献标志码］ A ［文章编号］ 1007⁃4368（2021）01⁃029⁃06
doi：10.7655/NYDXBNS20210106

Effect of urantide on the phosphorylation of STAT3 in the fatty livers of atherosclerotic rats

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CUI Haipeng ，LIN Yingxue ，WANG Yining ，WANG Tu ，LI Ying ，ZHAO Juan
Department of Pathophysiology，Chengde Medical University，Chengde 067000；Department of Pharmacy，Affiliated
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Hospital of Chengde Medical University，Chengde 067000，China

［Abstract］ Objective：To investigate the effect of urantide，a urotensin Ⅱ receptor antagonist，on the phosphorylation of signal
transducers and activators of transcription（STAT3）expression in the fatty liver of atherosclerosis（AS）rats. Methods：A total of 30
male Wistar rats were randomly divided into three groups：control group，AS group and Urantide group. The AS group and Urantide
group were induced by an intraperitoneal injection of vitamin D 3 （VD3 ）150 μg/（kg·d）for 3 days and by feeding with special high fat
food. Following successful modeling，the Urantide group was given urantide 30 μg/（kg·d）for 2 weeks by tail vein injection. The body
weight and liver weight of each rat were measured to calculate the liver index. HE staining was used to observe the morphological
change of the thoracic aortae and livers of the rats. Biochemical indexes were measured by detecting the change of alanine transaminase
（ALT）and aspartate aminotransferase（AST）in the serum of rats. The expression levels of STAT3 mRNA in liver tissues were detected
by RT⁃qPCR. The levels of STAT3 and p⁃STAT3 protein in liver tissues were detected by Western blot. Immunofluorescence was used
to detect the levels of p⁃STAT3 in the hepatocytes of each group. Results：Compared with the control group，the HE staining of the AS
group showed typical AS pathological change of thoracic aortae and typical steatosis of the livers；the liver indexes，the levels of ALT，
AST in the serum and the level of p⁃STAT3 in the livers increased significantly in the AS group. Compared with the AS group，the AS
pathological changes and the steatosis of the livers in the Urantide group were significantly alleviated；the liver indexes，the levels of
ALT，AST in the serum and the level of p⁃STAT3 in the livers decreased significantly in the Urantide group. In addition，no significant
changes were observed in the expression levels of STAT3 mRNA and protein in the liver tissues of each group. Conclusion：Urantide can

［基金项目］ 河北省自然科学基金（H2020406011）；河北省高等学校科学研究计划（ZD2019098）；河北省医学科学研究课题计
划（20200183）；承德医学院自然科学青年基金（201922）；河北省大学生创新创业训练计划（2018059）
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通信作者（Corresponding author），E⁃mail：zhaojuan@cdmc.edu.cn