Apelin对改善小鼠低氧性肺动脉高压的作用及与调节脂质代谢的关系

doi:10.12047/j.cjap.5601.2017.117

中国应用生理学杂志 ›› 2017, Vol. 33 ›› Issue (6): 493-496.doi: 10.12047/j.cjap.5601.2017.117

Apelin对改善小鼠低氧性肺动脉高压的作用及与调节脂质代谢的关系

陈然, 江璞, 刘玲燕, 高媛, 杨欣欣, 蔡卓长, 范小芳, 龚永生, 毛孙忠

温州医科大学低氧医学研究所, 浙江温州 325035

收稿日期:2017-02-04 修回日期:2017-10-19 出版日期:2017-11-28 发布日期:2018-06-19
基金资助:
浙江省自然科学基金项目（LY14H010005），浙江省教育厅科研项目（Y201326833），浙江省高等学校访问学者专业发展项目（FX2013084）

Apelin attenuates hypoxia induced pulmonary hypertension of mice through regulation of lipid metabolism

CHEN Ran, JIANG Pu, LIU Ling-yan, GAO Yuan, YANG Xin-xin, CAI Zhuo-chang, FAN Xiao-fang, GONG Yong-sheng, MAO Sun-zhong

Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou 325035, China

Received:2017-02-04 Revised:2017-10-19 Online:2017-11-28 Published:2018-06-19
Contact: 毛孙忠,Tel:0577-86699521;E-mail:wzlmao@126.com E-mail:wzlmao@126.com
Supported by:
浙江省自然科学基金项目（LY14H010005），浙江省教育厅科研项目（Y201326833），浙江省高等学校访问学者专业发展项目（FX2013084）

摘要/Abstract

摘要： 目的：探讨外源性apelin对小鼠慢性低氧性肺动脉高压的作用及其机制。方法：SPF级雄性apoE基因敲除（apoE-KO）小鼠30只，随机均分为3组（n=10），即常氧组、低氧组和低氧+apelin组，apelin组小鼠每天于低氧前经腹腔注射apelin-13（10 nmol/（kg·d）），其他组腹腔注射相同体积的生理盐水。采用常压连续低氧方法（9%~11% O₂，23 h/d）复制慢性低氧性肺动脉高压模型。低氧3周后，采用右心导管法测定小鼠右心室压（RVSP）和右心室与左心室加室间隔重量比，Elisa法检测血浆中高密度脂蛋白（HDL）、低密度脂蛋白（LDL）和总胆固醇（TC）的含量；real-time PCR法检测肝组织中三磷酸腺苷结合盒转运体A1（ABCA1）、清道夫受体B1（SR-B1）、低密度脂蛋白受体（LDLR）和3-羟基-3-甲基戊二酸单酰辅酶A还原酶（HMGCR）等基因的表达。Western blot法检测小鼠肺组织中过氧化物酶体增殖物激活受体γ（PPARγ）蛋白的表达。结果：①低氧组小鼠RVSP、RV/（LV+S）较常氧组分别高87%、85%（P均<0.05），apelin组小鼠RVSP、RV/（LV+S）较低氧组分别低39%、33%（P均<0.05）。②apelin组小鼠血浆中HDL-C含量、HDL/LDL比值分别较hypoxia组高21%、20%（P均<0.05），而血浆中TC、LDL-C含量两组间无显著差异（P均>0.05）。③apelin组小鼠肝组织中LDLR、SR-B1、ABCA1基因表达分别较低氧组上调241%、112%、69%（P均<0.05），而HMGCR基因表达下调45%（P<0.05）。④apelin组小鼠肺组织中PPARγ蛋白表达较低氧组上调47%。结论：Apelin可降低小鼠低氧性肺动脉高压，其机制与调节脂质代谢有关。

关键词: apelin, 脂质代谢, 肺动脉高压, 低氧, 小鼠

Abstract: Objective: To observe the role of apelin in the prevention of pulmonary hypertension induced by hypoxia in mice.Methods: Adult male apoE gene knockout (apoE-KO) mice were exposed to isobaric hypoxic chamber (9%~11% O₂, regular chow feed, 23 h/d)for 3 weeks to establish hypoxia-induced pulmonary hypertension. Thirty apoE-KO mice were randomly divided into normoxia group, hypoxia group and hypoxic with apelin (10 nmol/(kg·d), ip) group. The concentrations of high density lipoprotein (HDL), low density lipoprotein (LDL)and total cholesterol in plasma were detected by Elisa method. The mRNA levels of ATP-binding cassette transporter A1(ABCA1), low density lipoprotein receptor (LDLR), scavenger receptor class B1 (SR-B1), and HMG-CoA reductase (HMGCR)in liver were measured by real-time PCR. The protein level of peroxisome proliferators-activated receptor gamma (PPARγ) in lung was measured by Western blot.Results: ①The right ventricular systolic pressure (RVSP) and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV+S) of hypoxia group were significantly higher than those of normoxia group by 87% and 85% (P<0.05), respectively. RVSP and RV/(LV+S) of apelin group were significantly lower than those of hypoxia group by 39% and 33%(P<0.05), respectively. ②The plasma concentration of HDL and HDL/LDL of apelin group were significantly higher than those of hypoxia group by 21% and 20%(P<0.05), respectively. ③The mRNA levels of LDLR, SR-B1 and ABCA1 in liver of apelin group were significantly up-regulated than those of hypoxia group by 241%, 112% and 69% (P<0.05), respectively, while the mRNA level of HMGCR was down-regulated by 45% (P<0.05). ④The protein level of PPARγ in lung of apelin group was significantly up-regulated than that of hypoxia group by 47% (P<0.05).Conclusion: Apelin attenuates hypoxia-induced pulmonary hypertension of mice through regulation of lipid metabolism.

Key words: apelin, lipid metabolism, pulmonary hypertension, hypoxia, mice

陈然, 江璞, 刘玲燕, 高媛, 杨欣欣, 蔡卓长, 范小芳, 龚永生, 毛孙忠. Apelin对改善小鼠低氧性肺动脉高压的作用及与调节脂质代谢的关系[J]. 中国应用生理学杂志, 2017, 33(6): 493-496.

CHEN Ran, JIANG Pu, LIU Ling-yan, GAO Yuan, YANG Xin-xin, CAI Zhuo-chang, FAN Xiao-fang, GONG Yong-sheng, MAO Sun-zhong. Apelin attenuates hypoxia induced pulmonary hypertension of mice through regulation of lipid metabolism[J]. CJAP, 2017, 33(6): 493-496.

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Apelin对改善小鼠低氧性肺动脉高压的作用及与调节脂质代谢的关系

Apelin attenuates hypoxia induced pulmonary hypertension of mice through regulation of lipid metabolism

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