孕烷醇酮对应激性高血压大鼠血压的影响

Pregnanolone effects on the blood pressure of stress-induced hypertension in rats

实验探讨了孕烷醇酮(pregnanolone,PGN)对应激性高血压(stress-induced hypertension,SIH)大鼠血压影响的可能机制。采用电击足底结合噪声应激刺激的方法制备应激性高血压大鼠模型,观察每天应激刺激前腹腔注射PGN(0.24 mg/kg)对应激大鼠血压的影响,并观察PGN对应激刺激引起大鼠血中血管紧张素Ⅱ(angiotensin Ⅱ,Ang Ⅱ)含量和大鼠脑内Fos蛋白样免疫反应(FLI)神经元表达的影响。将动物随机分为正常对照组、应激1 h组、应激1 h+PGN组、应激15 d组和应激15 d+PGN组。实验结果如下:应激15 d+PGN组大鼠尾动脉收缩压升高幅值较应激15 d组大鼠尾动脉收缩压升高幅值明显降低(P<0.001)。同时,应激1 h组及应激15 d组血中Ang Ⅱ含量与对照组相比有显著升高(均P<0.001);应激1 h+PGN组及应激15 d+PGN组大鼠血中Ang Ⅱ含量分别显著低于应激1 h组及应激15 d组(均P<0.05);应激15 d组血中Ang Ⅱ含量较应激1 h组高(P<0.05)。正常对照组、应激15 d组、应激15 d+PGN组大鼠脑内仅见少数FLI神经元。与对照组相比,应激1 h组大鼠脑内外侧缰核(LHb)、内侧缰核(MHb)、室旁核(PVN)、杏仁中央核(CeA)和下丘脑外侧区(LH)等部位可见FLI神经元显著增加,而腹腔注射PGN后再应激1 h,可抑制上述效应。结果提示。

This study was conducted to determine the effect of pregnanolone (PGN) on blood pressure of a rat model of stress-induced hypertension (SIH). This model was established by applying electric shock to animal feet together with noise. PGN was administered intraperitoneally at 0.24 mg/kg·d-1 and blood pressure, angiotensin Ⅱ (Ang Ⅱ) levels, and the expression of Fos-like protein immunoreactive (FLI) neurons in brain areas were determined. Rats were randomly divided into five groups: (1) control, (2) stressed for 1 h, (3) stressed for 1 h after PGN pretreatment, (4) stressed for a 2 h session, twice a day, for 15 d, and (5) stressed for a 2 h session after PGN pretreatment, twice a day, for 15 d. The results showed that increased systolic pressure of tail artery caused by a 15-d stress treatment was significantly reduced by PGN pretreatment (P<0.001). Ang Ⅱ levels, measured by radioactive immunoreactivity, were significantly elevated (P<0.001) after the rats were stressed for 1 h or 15 d, the Ang Ⅱ level was significantly reduced by PGN treatment in both 1 h and 15 d stress groups (P<0.05). Only a small number of FLI neurons were found in the brain areas of the control group, 15 d stress group, and 15 d stress with PGN group. In the 1 h stress group, more FLI neurons were found in the lateral habenular nucleus, the medial habenular nucleus, the paraventricular nucleus, the central nucleus of amgydaloid and the lateral hypothalamus compared with the control group. PGN pretreatment significantly prevented the increase in the number of FLI neurons. These results indicate that PGN pretreatment prevents elevation of tail artery systolic pressure in SIH rats and that this effect of PGN may be mediated through reducing Ang 11 level and inhibiting the activity of cardiovascular center involved in stress.