Department of Neurosurgery, First Hospital of Jilin University, Jilin, China.
Department of Emergency Medicine, First Hospital of Jilin University, Jilin, China.
Curr Pharm Des. 2018;24(44):5342-5347. doi: 10.2174/1381612825666190206224134.
Ulinastatin (UTI) plays the beneficial roles in modifying cerebral ischemic injury evoked by cardiac arrest (CA). XueBiJing (XBJ), comprised of extracts from Chinese herbals, has been used for the treatment of sepsis and ischemic disorders linked to multiple organ dysfunction syndromes. The current study was to find interventions that can enhance effectiveness of these drugs and further to provide a fundamental for their rational application in clinical practice. Thus, we examined how apoptosis signal in the hippocampus is engaged in a facilitating role of UTI and XBJ in improving neural injury and neurological functions after transient cerebral ischemia.
CA was induced by asphyxia followed by cardiopulmonary resuscitation in rats. Western Blot analysis and ELISA were employed to determine the protein expression of Caspase-3 and Caspase-9 in the hippocampus; and representative apoptosis pathways. The modified neurological severity score (mNSS) and spatial working memory performance were used to assess neurological deficiencies in CA rats.
CA increased Caspase-3 and Caspase-9 in the hippocampus CA1 region. A lower dose of UTI did not attenuate upregulation of apoptosis signal pathways evoked by CA. However, a systemic administration of XBJ significantly amplified the inhibitory effects of the lower dose of UTI on apoptosis signal of the hippocampus. In addition, a combination of UTI and XBJ improved mNSS and spatial working memory performance to a greater degree.
Our data indicate that a combination of XBJ and UTI plays a facilitating role in improving neuronal injury and neurological deficits observed in transient cerebral ischemia; and an inhibition of apoptosis signal pathways is involved in neuroprotective effects of united XBJ and UTI.
尿胰蛋白酶抑制剂（UTI）在修饰心脏骤停（CA）引起的脑缺血损伤方面发挥有益作用。血必净（XBJ）由草药提取物组成，用于治疗与多器官功能障碍综合征相关的败血症和缺血性疾病。本研究旨在寻找能够增强这些药物疗效的干预措施，并为其在临床实践中的合理应用提供基础。因此，我们研究了在短暂性脑缺血后，UTI 和 XBJ 如何通过激活海马中的凋亡信号，促进神经损伤和神经功能的恢复。
采用窒息联合心肺复苏法诱导大鼠 CA，Western blot 分析和 ELISA 检测海马中 Caspase-3 和 Caspase-9 蛋白表达，确定代表性凋亡途径；改良神经功能严重程度评分（mNSS）和空间工作记忆能力评估 CA 大鼠的神经功能缺损。
CA 增加了海马 CA1 区的 Caspase-3 和 Caspase-9。低剂量 UTI 不能减轻 CA 引起的凋亡信号通路的上调，但 XBJ 的全身给药显著增强了低剂量 UTI 对海马凋亡信号的抑制作用。此外，UTI 和 XBJ 的联合使用在更大程度上改善了 mNSS 和空间工作记忆能力。
我们的数据表明，XBJ 和 UTI 的联合使用在改善短暂性脑缺血后观察到的神经元损伤和神经功能缺陷方面发挥促进作用；抑制凋亡信号通路参与了 XBJ 和 UTI 联合使用的神经保护作用。
