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中国应用生理学杂志 ›› 2022, Vol. 38 ›› Issue (3): 252-257.doi: 10.12047/j.cjap.6192.2022.038

• 研究论文 • 上一篇    下一篇

抗逆转录病毒药对孕育期雌鼠心血管影响*

余海娟1,2, 陈祖盛1, 陈彤2, 吴燚晶2, 孙珂悦2, 李昱静2, 徐钦3, 叶寒辉4, 陈雅红4, 阮琴韵5, 傅丽云5, 黄春燕5, 周琳瑛6, 汪敏华7, 方秋娟1△   

  1. 1.福建医科大学基础医学院生理学与病理生理学系 心血管病离子通道信号调控福建省高校重点实验室, 2.临床医学部, 3.护理学院, 4.孟超肝胆医院, 5.附属第一医院超声科, 6.公共技术中心电镜室, 福建 福州 350108;
    7.福建中医药大学附属第二人民医院妇产科, 福建 福州 350108
  • 收稿日期:2021-03-18 修回日期:2022-05-03 出版日期:2022-05-28 发布日期:2022-09-05
  • 通讯作者: Tel: 15980234523; E-mail: 1143889484@qq.com
  • 基金资助:
    *福建省自然科学基金项目(2014J01329);福建医科大学教授基金(JS14004);福建医科大学大学生创新创业训练项目(C19070)

Adverse cardiovascular effects of antiretrovirals in female mice during gestation

YU Hai-juan1,2, CHEN Zu-sheng1, CHEN Tong2, WU Yi-jing2, SUN Ke-yue2, LI Yu-jing2, XU Qin3, YE Han-hui4, CHEN Ya-hong4, RUAN Qin-yun5, FU Li-yun5, HUANG Chun-yan5, ZHOU Lin-ying6, WANG Min-hua7, FANG Qiu-juan1△   

  1. 1. The Key Laboratory of Fujian Province University on Ion Channel and Signal Transduction in Cardiovascular Disease, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fujian Medical University;
    2. Department of Clinical Medicine, Fujian Medical University;
    3. School of Nursing, Fujian Medical University;
    4. Mengchao Hepatobiliary Hospital of Fujian Medical University;
    5. Department of Ultrasound, The First Affiliated Hospital of Fujian Medical University;
    6. Electron Microscopy Lab of Public Technology Service Center, Fujian Medical University;
    7. Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China
  • Received:2021-03-18 Revised:2022-05-03 Online:2022-05-28 Published:2022-09-05

摘要: 目的: 评价抗逆转录病毒药对孕育期雌性大鼠心血管功能及某些生化指标的影响。方法: SD大鼠9周龄雌鼠19只、10周龄雄鼠6只,9只/10只雌鼠与3只雄鼠合1笼,共2笼,分为正常对照组(CON)、高效抗逆转录病毒治疗组(HARRT)。其中CON组雌性大鼠每天早、晚生理盐水 (10 ml/kg)灌胃,HARRT组雌性大鼠灌等容积抗逆转录病毒药(AZT 31.25 mg/kg +3TC 15.63 mg/kg +LPV/r (41.67/10.42) mg/kg),连续3个月。记录雌性大鼠体重、存活情况;检测超声心动图,多导生理记录仪检测动脉血压、心脏血流动力学参数;相应试剂盒检测血糖、血脂四项、心肌酶及肝酶;Masson染色及透射电镜分别观察心肌胶原纤维和心肌细胞超微结构。结果: CON组雌性大鼠均存活(9/9),HARRT组雌性大鼠存活6只(6/10);与CON组比较,HAART组雌性大鼠体重减少(P< 0.01);LVDd、IVST、LVPWT、LAD增加(P<0.05);动脉舒张压增加(P<0.05)、LVP +dP/dtmax减少(P<0.01);TG减少、Glu增加(P<0.05)、CK减少(P<0.01)、GOT减少(P<0.05);心肌组织胶原纤维增多,心肌细胞超微结构异常。结论: 抗逆转录病毒药可导致孕育期雌性大鼠心血管病变。

关键词: 雌鼠大鼠, 孕育期, 高效抗逆转录病毒治疗, 心血管不良反应

Abstract: Objective: To evaluate the effects of antiretrovirals on cardiovascular function and some biochemical indexes in gestational female rats. Methods: Nineteen 9-week-old female and six 10-week-old male SD rats were divided into normal control group (CON) and highly active antiretroviral therapy group (HARRT), 9/10 female rats and 3 male rats were combined into one cage, totally 2 cages. Female rats in CON group were intragastrically given with normal saline (NS, 10 ml/kg) every morning and evening, while female rats in HARRT group were treated with equal volume antiretrovirals (AZT 31.25 mg/kg + 3TC 15.63 mg/kg + LPV/r (41.67/10.42) mg/kg) for 3 months. The body weight and survival rate of female rats were recorded. Echocardiography and multichannel physiological recorder were used to detect arterial blood pressure and cardiac hemodynamic parameters. The levels of blood glucose, blood lipids, myocardial enzymes and liver enzymes were detected by corresponding kits. Myocardial collagen fibers were observed by Masson staining and the ultrastructure of myocardial cells were observed by transmission electron microscopy. Results: All female rats in CON group survived (9/9), while only 6 rats in HARRT group survived (6/10). Compared with CON group, the body weight of female rats in HAART group was decreased significantly(P<0.01); the levels of left ventricular end diastolic diameter (LVDd), interventricular septal thickness (IVST), thickness of left ventricular posterior wall (LVPWT) , left atrial diameter (LAD) and arterial diastolic pressure were increased significantly (P<0.05); the level of LVP+dP/dtmax was decreased (P<0.01). The levels of triglyceride, creatine kinase, and glutamic oxaloacetic transaminase were decreased (P<0.05 or P<0.01), while the level of glucose was increased (P<0.05). The collagen fibers were increased in myocardial tissue, and ultrastructure of myocardial cells was abnormal. Conclusion: Antiretrovirals during gestation can cause cardiovascular diseases in female rats.

Key words: female rats, gestational period, highly active anti-retroviral therapy, adverse cardiovascular reactions

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