O'Shaughnessy C T, Rothwell N J, Shrewsbury-Gee J
Department of Physiological Sciences, University of Manchester, U.K.
Can J Physiol Pharmacol. 1989 Oct;67(10):1345-50. doi: 10.1139/y89-214.
Effects of a stable analogue of thyrotrophin-releasing hormone, RX77368, on cerebral blood flow and infarct size have been studied in an acute model of cerebral ischaemia in the rat. Two hours after electrocoagulation of the left middle cerebral artery (MCA), the mean area of ischaemia (+/- SEM), determined histochemically, was 11.5 +/- 2.2% of a single hemisphere and blood flow, determined using radiolabelled microspheres, was reduced by 40% in the left forebrain (p less than 0.001 compared with sham-operated animals). Administration of RX77368 (50 micrograms/kg, intracerebroventricularly) within 10 min of arterial occlusion caused a significant (p less than 0.01) reduction in mean lesion size to 3.7 +/- 1.8% and stimulation of blood flow to the left ischaemic forebrain (60% above saline treated). Peripheral administration of RX77368 (1 mg/kg intraperitoneally) also significantly stimulated blood flow to the ischaemic forebrain and caused an apparent decrease in frequency of large infarcted areas of brain tissue, although mean lesion size was not significantly affected. These findings indicate that RX77368 ameliorates tissue damage in acute focal cerebral ischaemia. Such effects may be related to stimulation of cerebral blood flow.
促甲状腺激素释放激素的稳定类似物RX77368对大鼠急性脑缺血模型脑血流量和梗死面积的影响已得到研究。在电凝大鼠左大脑中动脉(MCA)两小时后,通过组织化学方法测定的平均缺血面积(±标准误)为单个半球的11.5±2.2%,使用放射性微球测定的血流量在左前脑减少了40%(与假手术动物相比,p<0.001)。在动脉闭塞后10分钟内脑室内给予RX77368(50微克/千克)可使平均损伤面积显著(p<0.01)减小至3.7±1.8%,并刺激左缺血前脑的血流量(比生理盐水处理组高60%)。腹腔内给予RX77368(1毫克/千克)外周给药也显著刺激了缺血前脑的血流量,并使脑组织大面积梗死区域的频率明显降低,尽管平均损伤面积没有受到显著影响。这些发现表明,RX77368可改善急性局灶性脑缺血中的组织损伤。这种作用可能与刺激脑血流量有关。