Gibson Tiffini C, Phernetton Terrance M, Wiltbank Milo C, Magness Ronald R
Department of Obstetrics and Gynecology, University of Wisconsin, Madison, 53706, USA.
Biol Reprod. 2004 Jun;70(6):1886-94. doi: 10.1095/biolreprod.103.019901. Epub 2004 Feb 25.
The objective of the current study was to develop an ovine animal model for consistent study of uterine blood flow (UBF) changes during synchronized ovarian cycles regardless of season. Sheep were surgically bilaterally instrumented with uterine artery blood flow transducers and 5-7 days later implanted with a vaginal progesterone (P(4))-controlled internal drug-releasing device (CIDR; 0.3 g) for 7 days. On Day 6 of P(4), sheep were given two prostaglandin F(2 alpha) injections (7.5 mg i.m. 4 h apart). At CIDR removal, Experimental Day 0, zero (n = 9), 500 IU (n = 8), or 1000 IU (n = 7) eCG was injected i.m.; UBF was monitored continuously for 55-75 h. Jugular blood was sampled every 8 h to evaluate levels of P(4), estradiol-17 beta (E(2)beta) and luteinizing hormone (LH). The inhibitor of nitric oxide synthase, L-nitro-arginine methyl ester (L-NAME) was infused in a stepwise fashion unilaterally into one uterine artery at 48-50 h after 500 IU eCG and the effects on UBF were examined (n = 7). The zero-eCG group gradually increased UBF from a baseline of 17.4 +/- 3.9 to 80.5 +/- 1.1 ml/min. The 500-IU-eCG group increased UBF between 10 and 15 h from a baseline of 11 +/- 3.3 to 83.3 +/- 1.0 ml/min, whereas UBF for the 1000-IU-eCG group was higher (100.1 +/- 1.7 ml/min) than that seen in either of the other groups. Plasma P(4) fell to baseline within 8 h of CIDR removal, while E(2)beta rose gradually in association with elevations in UBF. LH surges occurred between 32 and 56 h after CIDR removal and the LH surge occurred earlier in the 1000-IU-eCG group than the other two groups (P < 0.01). L-NAME infusion dose dependently reduced maximum levels of UBF ipsilaterally by 54.6% +/- 6.2%, but contralaterally only by 27.4% +/- 8.5%. Regardless of season, either dose of eCG will result in analogous UBF responses. During the follicular phase, elevations in UBF are in part locally controlled by the de novo production of nitric oxide.
本研究的目的是建立一种绵羊动物模型，以便在不受季节影响的同步卵巢周期中持续研究子宫血流量（UBF）的变化。对绵羊进行双侧手术，植入子宫动脉血流传感器，5 - 7天后植入阴道孕酮（P(4)）控制的内部药物释放装置（CIDR；0.3 g），持续7天。在P(4)处理的第6天，给绵羊肌肉注射两次前列腺素F(2α)（7.5 mg，间隔4小时）。在取出CIDR时，即实验第0天，肌肉注射0（n = 9）、500 IU（n = 8）或1000 IU（n = 7）的eCG；连续监测UBF 55 - 75小时。每8小时采集颈静脉血样，以评估P(4)、雌二醇-17β（E(2)β）和促黄体生成素（LH）的水平。在注射500 IU eCG后48 - 50小时，将一氧化氮合酶抑制剂L-硝基-精氨酸甲酯（L-NAME）逐步单侧注入一条子宫动脉，检查其对UBF的影响（n = 7）。零eCG组的UBF从基线的17.4±3.9逐渐增加到80.5±1.1 ml/分钟。500 IU eCG组在10至15小时内UBF从基线的11±3.3增加到83.3±1.0 ml/分钟，而1000 IU eCG组的UBF（100.1±1.7 ml/分钟）高于其他两组中的任何一组。血浆P(4)在取出CIDR后8小时内降至基线，而E(2)β随着UBF的升高逐渐上升。LH高峰出现在取出CIDR后32至56小时，1000 IU eCG组的LH高峰比其他两组更早出现（P < 0.01）。注入L-NAME后，同侧UBF的最大水平剂量依赖性地降低了54.6%±6.2%，但对侧仅降低了27.4%±8.5%。无论季节如何，两种剂量的eCG都会导致类似的UBF反应。在卵泡期，UBF的升高部分受一氧化氮从头产生的局部控制。
