Ohtaki Hirokazu, Dohi Kenji, Yofu Sachiko, Nakamachi Tomoya, Kudo Yoshifumi, Endo Sakura, Aruga Tohru, Goto Noboru, Watanabe Jun, Kikuyama Sakae, Shioda Seiji
Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo 142-8555, Japan.
Regul Pept. 2004 Dec 15;123(1-3):61-7. doi: 10.1016/j.regpep.2004.05.013.
It has been reported that pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in preventing neuronal cell death and is also a potent vasodilator. Cerebral hypotension and hypoperfusion during cerebral ischemia and neurodegenerative diseases are well known as some of the negative factors which aggravate neuronal cell death. Nevertheless, the effect of PACAP on the cerebral circulation was not understood well. Therefore, in the present study, we determined the mean arterial blood pressure (MBP), regional cerebral blood flow (rCBF) and cerebral oxygen content (pO2) in mice, and estimated the therapeutically useful doses of PACAP. Under barbiturate anesthesia, polyethylene tubes were inserted into mice to monitor MBP and to administer PACAP (5 x 10(-13)-5 x 10(-8) mol/kg) or vasoactive intestinal peptide (VIP; 5 x 10(-12) and 5 x 10(-9) mol/kg). Then, MBP, rCBF and cerebral pO2 were simultaneously measured in the mice. PACAP (5 x 10(-10)-5 x 10(-9) mol/kg) injections transiently decreased MBP, and cerebral pO2. PACAP (5 x 10(-8) mol/kg) injections produced a long-lasting potent decline of MBP, rCBF and cerebral pO2. Therefore, PACAP should be applied at low doses which do not influence the MBP and cerebral circulation to determine the therapeutically useful doses of PACAP for neuroprotection.
据报道，垂体腺苷酸环化酶激活多肽（PACAP）在预防神经元细胞死亡中起重要作用，并且还是一种强效血管舒张剂。脑缺血和神经退行性疾病期间的脑低血压和低灌注是加重神经元细胞死亡的一些负面因素，这是众所周知的。然而，PACAP对脑循环的影响尚未得到很好的理解。因此，在本研究中，我们测定了小鼠的平均动脉血压（MBP）、局部脑血流量（rCBF）和脑氧含量（pO2），并估计了PACAP的治疗有效剂量。在巴比妥类麻醉下，将聚乙烯管插入小鼠体内以监测MBP并给予PACAP（5×10^(-13)-5×10^(-8)mol/kg）或血管活性肠肽（VIP；5×10^(-12)和5×10^(-9)mol/kg）。然后，同时测量小鼠的MBP、rCBF和脑pO2。注射PACAP（5×10^(-10)-5×10^(-9)mol/kg）会使MBP和脑pO2短暂下降。注射PACAP（5×10^(-8)mol/kg）会使MBP、rCBF和脑pO2产生持久的显著下降。因此，应在不影响MBP和脑循环的低剂量下应用PACAP，以确定PACAP用于神经保护的治疗有效剂量。
