血管紧张素AT1受体抗体阳性孕鼠后代高盐饮食后血管功能障碍(英文)

Vascular dysfunction in the offspring of AT1 receptor antibody-positive pregnant rats during high-salt diet

血管紧张素AT1受体抗体(AT1-Ab)可损伤胎盘发育,进而导致胎儿宫内生长受限(intrauterine growth restriction,IUGR)。根据胎儿源性成人疾病学说,IUGR会明显增加成人后患心血管疾病的几率。本研究旨在观察AT1-Ab阳性孕鼠后代生长至成年后血管功能有无异常。24只雌性Wistar大鼠(8周龄、AT1-Ab阴性)随机平均分为对照组和免疫组。免疫组雌鼠用主动免疫方法建立AT1-Ab阳性模型,而对照组用没有抗原的免疫佐剂处理。接受免疫后第8周时用酶联免疫吸附实验(ELI-SA)检测雌鼠血清中AT1-Ab水平。随后,上述雌鼠与正常Wistar雄鼠交配后受孕。免疫组和对照组后代鼠40周龄时,给予轻度高盐饮食喂养(基础饲料中添加4%的NaCl)共12周。无创血压仪监测后代鼠血压,离体血管环实验检测血管功能和反应性。结果显示,免疫组雌鼠8周后血清中抗体滴度达顶峰,与对照组雌鼠相比,差异极显著(光密度值:2.75±0.08vs0.33±0.01,P<0.01)。免疫组后代血压与对照组相比未见显著升高,但其胸主动脉血管环对去甲肾上腺素的血管收缩反应与对照组后代鼠相比显著降低(P<0.01),而且对乙酰胆碱的血管舒张反应与对照组后代鼠相比也显著下降(P<0.05)。以上结果提示,在相同高盐饮食喂养条件下,AT1-Ab阳性雌鼠的后代易于出现血管功能异常。

Antibody against the angiotensin AT1 receptor（AT1-Ab） could disturb placental development.The placenta is the key organ between mother and fetus.Placental damage will seriously impair fetal growth and development in utero,leading to intrauterine growth restriction（IUGR）.Based on the fetal origins of adult disease（FOAD） hypothesis,IUGR could increase a propensity to develop adult onset cardiovascular disease（CVD）.The present study was designed to determine whether vascular function has changed in the adult offspring of AT1-Ab positive pregnant rats.Twenty four female rats（8-week-old,AT1-Ab negative） were randomly divided into two groups,immunized and vehicle groups.Immunized group received active immunization to establish AT1-Ab-positive model,while vehicle group was subjected to Freund＇s adjuvant without antigen.After 8 weeks of immunization,the antibody titers in sera from the female rats were detected by enzyme-linked immunosorbent assay（ELISA）.Then all the female rats were mated with normal Wistar male rats and became pregnant.Immunized/vehicle group offspring rats（I offspring/V offspring） were raised to 40-week-old under standard chow feeding.Then the two groups＇ offspring rats were given a high-salt diet for 12 weeks（4% NaCl in chow feed-ing）.Systolic blood pressure（SBP） was measured dynamically by noninvasive blood pressure system.The vascular ring experiment was performed to detect vascular function and reactivity.As detected by ELISA,the titers of antibody peaked at the 8th week（OD values：2.75±0.08 vs 0.33±0.01,P0.01 vs vehicle group at the same time point）.There was no significant difference of SBP between the two groups＇ offspring rats during the high-salt diet（P0.05）.Isolated thoracic aortic rings of I offspring had significantly de-creased constriction under norepinephrine treatment（P0.01 vs V offspring） and significantly decreased dilation under acetylcholine treatment（P0.05 vs V offspring）.These results suggest that the offspring of AT1-Ab-positive pregnant rats are more susceptible to vascular functional abnormality while being fed high-salt diet.