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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。
Angiotensin AT1 receptor antibody (AT1-Ab) can damage placental development, leading to intrauterine growth restriction (IUGR). According to the theory of fetal-derived adult disease, IUGR significantly increases the risk of developing cardiovascular disease in adults. The aim of this study was to investigate whether there is any abnormality of blood vessel function in the offspring of AT1-Ab positive pregnant rats after their growth to adulthood. Twenty-four female Wistar rats (8 weeks old, negative for AT1-Ab) were randomly divided into control and immunized groups. In the immunized group, the AT1-Ab positive model was established by active immunization, while the control group was treated with immune adjuvant without antigen. At the 8th week after immunization, the serum level of AT1-Ab in female rats was detected by enzyme-linked immunosorbent assay (ELI-SA). Subsequently, the females and normal Wistar male mice after mating pregnant. Mice in the immunized and control groups were fed a mild high salt diet (4% NaCl in the basal diet) for 12 weeks at 40 weeks of age. Noninvasive blood pressure monitor offspring blood pressure, isolated vascular ring test to detect vascular function and reactivity. The results showed that the titer of antibody in the serum of the immunized group reached its peak at 8 weeks, which was significantly different from that in the control group (OD = 2.75 ± 0.08 vs 0.33 ± 0.01, P <0.01). Blood pressure in the offspring of the immunized group was not significantly higher than that of the control group, but the vasoconstriction of norepinephrine in the thoracic aortic ring was significantly lower than that in the control group (P <0.01) Vasodilatory responses were also significantly decreased compared with control rats (P <0.05). The above results suggest that the offspring of AT1-Ab positive female mice are prone to vascular dysfunction under the same high-salt diet.