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大量研究显示雌激素通过传统核受体ERα或ERβ以及新型膜受体——G蛋白耦联雌激素受体(G protein coupled estrogen receptor,Gper)对心血管系统起多方面保护作用。然而,文献报道的Gper基因敲除(Gper-knockout,Gper-KO)小鼠心血管系统表型差异很大。本研究旨在揭示Gper-KO对大鼠动脉血压和心率的影响。GperKO SD大鼠系采用CRISPR-Cas9基因编辑技术制备。我们对10周龄雄性Gper-KO大鼠(n=6)、12周龄雌性Gper-KO大鼠(n=6)以及同龄野生型(wild type,WT)大鼠(雌雄各6只),在清醒和束缚制动条件下进行无创检测尾动脉血压,连续检测8~9天,继而又在戊巴比妥麻醉下直接测量股动脉血压。WT雄性大鼠的尾动脉血压在第1至第4天略高于第5至第9天,表明在实验初期束缚应激引起的交感系统兴奋使大鼠血压升高,随着大鼠对束缚应激的逐步适应,其血压恢复至正常水平。雄性或雌性Gper-KO大鼠的动脉血压在实验初期都高于WT组(雄性大鼠:第1天至第5天;雌性大鼠:第1天至第3天),而随后几天的血压与WT组之间没有明显差异。雄性Gper-KO大鼠的心率高于雄性WT大鼠,雄性和雌性Gper-KO大鼠的体重增加值均较WT组大鼠减少。在麻醉状态下,Gper-KO组和WT组大鼠动脉血压无明显差异。以上结果表明,Gper-KO大鼠可能对应激性交感系统兴奋更为敏感,提示Gper在应激状态下的心血管功能调节中发挥重要作用。
Numerous studies have shown that estrogen plays a multifactorial role in the cardiovascular system through the traditional nuclear receptors ERα or ERβ and the novel membrane receptor G protein-coupled estrogen receptor (Gper). However, Gper-knockout (Gper-KO) mice reported in the literature have very different cardiovascular phenotypes. The aim of this study was to reveal the effects of Gper-KO on arterial blood pressure and heart rate in rats. GperKO SD rats were prepared using the CRISPR-Cas9 gene editing technique. We evaluated the effects of 10-week-old male Gper-KO rats (n = 6), 12-week old female Gper-KO rats (n = 6) and wild-type (WT) Non-invasive detection of caudal arterial blood pressure during conscious and restrained braking was performed continuously for 8-9 days followed by direct measurement of femoral artery blood pressure under pentobarbital anesthesia. The caudal arterial blood pressure in WT male rats was slightly higher from day 5 to day 9 on days 1 to 4 indicating that the sympathetic activation of the restraint-induced stress increased rat blood pressure at the beginning of the experiment, The gradual adjustment of stress, the blood pressure returned to normal levels. Arterial blood pressure in male or female Gper-KO rats was significantly higher in WT than in WT (male rats: day 1 to day 5; female rats: day 1 to day 3) during the first few days There was no significant difference between the blood pressure and the WT group. The heart rate of male Gper-KO rats was higher than that of male WT rats, and the body weight gain of male and female Gper-KO rats was lower than that of WT rats. Under anesthesia, there was no significant difference in arterial blood pressure between Gper-KO group and WT group. The above results indicate that Gper-KO rats may be more sensitive to the excitement of stress sympathetic system, suggesting that Gper plays an important role in the regulation of cardiovascular function under stress.