孕期运动对自发性高血压大鼠子代肾脏纤维化及AngⅡ/TGF-β1/CTGF信号通路的影响  

Effects of exercise during pregnancy on renal fibrosis and AngⅡ/TGF-β1/CTGF signaling pathway in offspring of spontaneously hypertensive rats

作　　者：刘霜 高腾 孙华灵[1] 张严焱 石丽君[1,2,3] LIU Shuang;GAO Teng;SUN Hualing;ZHANG Yanyan;SHI Lijun(Department of Exercise Physiology,Beijing Sport University,Beijing 100084,China;Laboratory of Sports Stress and Adaptation of General Administration of Sport of China,Beijing 100084,China;Key Laboratory of Physical Fitness and Exercise,Ministry of Education,Beijing 100084,China)

机构地区：[1]北京体育大学运动生理学教研室,北京市100084 [2]国家体育总局运动应激适应重点实验室,北京市100084 [3]北京体育大学运动与体质健康教育部重点实验室,北京市100084

出　　处：《中国动脉硬化杂志》2025年第1期16-23,共8页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金项目(32071174);中央高校基本科研业务费专项资金(2024JCYJ001、2024YJSY002、2023013)。

摘　　要：[目的]探讨孕期运动对自发性高血压大鼠(SHR)3月龄子代肾脏结构、功能及肾脏局部血管紧张素Ⅱ(AngⅡ)/转化生长因子β1(TGF-β1)/结缔组织生长因子(CTGF)信号通路的影响,旨为高血压生命早期干预和关键靶器官保护提供实验依据。[方法]将SHR和WKY大鼠进行雌雄配种后的孕鼠随机分为孕期安静组(p-WKY-SED、p-SHR-SED)和孕期运动组(p-WKY-EX、p-SHR-EX)。选择3月龄子代大鼠为研究对象,采用尾动脉无创血压系统、比色法分别检测3月龄子代大鼠的血压、血清尿素氮和肌酐。HE染色、Masson染色、ELISA、Western blot分别检测3月龄子代大鼠的肾脏结构、胶原容积分数、AngⅡ浓度、肾素-血管紧张素-醛固酮系统(RAAS)和致纤维化信号通路相关蛋白表达。[结果](1)无论雌雄,p-SHR-SED组子代大鼠的收缩压(SBP)、舒张压(DBP)和平均动脉压(MAP)均显著高于p-WKY-SED组;孕期运动可显著降低雄性子代大鼠的SBP、DBP和MAP(P<0.05),而对雌性子代大鼠无影响(P>0.05)。(2)各组间血清尿素氮和肌酐无显著差异(P>0.05)。(3)无论雌雄,p-SHR-SED组子代大鼠的肾小球体积、肾脏胶原容积分数显著高于p-WKY-SED组;孕期运动后,p-SHR-EX组子代大鼠的肾小球体积、肾脏胶原容积分数显著降低(P<0.05)。(4)无论雌雄,p-SHR-SED组子代大鼠的肾脏AngⅡ显著高于p-WKY-SED组;孕期运动后,p-SHR-EX组子代大鼠的肾脏AngⅡ明显减少(P<0.05)。(5)无论雌雄,p-SHR-SED组子代大鼠的血管紧张素Ⅱ1型受体(AT1R)、TGF-β1、CTGF蛋白表达均显著高于p-WKY-SED组,而血管紧张素转换酶2(ACE2)、血管紧张素Ⅱ2型受体(AT2R)、MasR蛋白表达显著低于p-WKY-SED(P<0.05);孕期运动后,p-SHR-EX组雄性子代大鼠的AT1R、TGF-β1、CTGF蛋白表达显著减少,ACE2、AT2R、MasR蛋白表达升高,雌性子代大鼠的AT1R、TGF-β1蛋白表达显著减少(P<0.05)。[结论](1)孕期运动可显著降低高血压大鼠3月龄雄性子代大鼠的血�Aim To explore the effects of exercise during pregnancy on renal structure,function and angiotensinⅡ(AngⅡ)/transforming growth factor-β1(TGF-β1)/connective tissue growth factor(CTGF)signaling pathway in 3-month-old offspring of spontaneously hypertensive rats(SHR),the aim of this study was to provide experimental basis for early intervention of hypertension and protection of key target organs.Methods After mating SHR and WKY rats,pregnant rats were randomly divided into sedentary group(p-WKY-SED,p-SHR-SED)and exercise group(p-WKY-EX,p-SHR-EX).Blood pressure,serum urea nitrogen and creatinine were measured by caudal artery non-invasive blood pressure system and colorimetry in 3-month-old offspring rats.HE staining,Masson staining,ELISA and Western blot were used to detect the renal structure,collagen volume fraction,AngⅡconcentration,renin-angiotension-aldosterone system(RAAS)and protein expression related to fibrogenic signal pathway in 3-month-old rats.Results(1)The systolic blood pressure(SBP),diastolic blood pressure(DBP)and mean arterial pressure(MAP)of offspring rats in p-SHR-SED group were significantly higher than those in p-WKY-SED group.The SBP,DBP and MAP of SHR male offspring rats were significantly decreased by exercise during pregnancy(P<0.05),but had no effect on the female offspring rats(P>0.05).(2)There was no significant difference in serum urea nitrogen and creatinine among the groups(P>0.05).(3)The glomerular volume and the collagen volume fraction in p-SHR-SED group were significantly higher than those in p-WKY-SED group(P<0.05),and the glomerular volume and the collagen volume fraction in p-SHR-EX group were significantly lower than those in p-SHR-SED group(P<0.05).(4)Renal AngⅡlevel of offspring rats in p-SHR-SED group was significantly higher than that in p-WKY-SED group,and renal AngⅡlevel of offspring rats in p-SHR-EX group was significantly lower than that in p-SHR-SED group(P<0.05).(5)The expression levels of angiotensinⅡtype 1 receptor(AT1R),TGF-β1 and CTGF protein in p-

关 键 词：孕期运动 自发性高血压 子代 肾脏纤维化 AngⅡ/TGF-β1/CTGF信号通路 

分 类 号：R5[医药卫生—内科学] R363[医药卫生—临床医学]