Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, People's Republic of China.
Metab Brain Dis. 2012 Dec;27(4):495-505. doi: 10.1007/s11011-012-9330-x. Epub 2012 Jul 29.
The calcium sensitizers levosimendan and piperphentonamine hydrochloride (PPTA) are used as cardiovascular drugs for treatment of heart failure. Given that levosimendan has been reported to exhibit a neuroprotective profile in a model of traumatic brain injury, it was interesting to know whether PPTA, a new calcium sensitizer recently developed in China, exerts a similar effect. The objective of this study was to determine whether PPTA exhibited neuroprotective effects and whether these properties were associated with memory. Four-vessel occlusion (4-VO) was used to induce global cerebral ischemia/reperfusion injury in rats treated with or without PPTA (5, 10 mg/kg, i.p., 2 h after the onset of reperfusion and then once a day for 15 consecutive days). Memory was measured using the step-through passive avoidance test. Neurochemical changes were examined in rat PC12 cells treated with oxygen-glucose deprivation (OGD) for 4 h followed by reoxygenation (OGD-R) for 24 h, in the absence or presence of PPTA. In vehicle-treated animals, 4-VO for 10 min produced memory deficits, as demonstrated by decreased retention in step-through passive avoidance, and massive neuron loss in the hippocampal CA1 subregion. These effects were attenuated by PPTA. The results were consistent with those observed in PC12 cells. PPTA treatment increased cell viability, as indicated by MTT assay, inhibited apoptosis, and decreased extracellular lactate dehydrogenase levels in Na(2)S(2)O(4)-treated PC12 cells. These results provide novel demonstration for the ability of PPTA to attenuate cerebral ischemia-induced memory deficits via neuroprotection in the hippocampus. The neuroprotective effect of PPTA appears to be associated with its anti-apoptotic activity. PPTA has the therapeutic potential for ischemic stroke.
钙增敏剂左西孟旦和盐酸哌酚嗪（PPTA）被用作治疗心力衰竭的心血管药物。鉴于左西孟旦在创伤性脑损伤模型中显示出神经保护作用，因此很想知道中国最近开发的新型钙增敏剂 PPTA 是否具有类似的作用。本研究旨在确定 PPTA 是否具有神经保护作用，以及这些特性是否与记忆有关。四血管闭塞（4-VO）用于诱导用或不用 PPTA（5、10mg/kg，ip，再灌注后 2 小时开始，然后连续 15 天每天一次）处理的大鼠全脑缺血/再灌注损伤。使用穿梭被动回避测试测量记忆。在氧葡萄糖剥夺（OGD）4 小时后再氧合（OGD-R）24 小时的情况下，在没有或存在 PPTA 的情况下，在大鼠 PC12 细胞中检查神经化学变化。在 vehicle 处理的动物中，4-VO 10 分钟导致记忆缺陷，如穿梭被动回避中的保留时间减少和海马 CA1 亚区中的大量神经元丢失所证明。这些作用被 PPTA 减弱。结果与在 PC12 细胞中观察到的结果一致。PPTA 处理通过增加 MTT 测定的细胞活力，抑制凋亡并降低 Na 2 S 2 O 4 处理的 PC12 细胞中的细胞外乳酸脱氢酶水平来发挥作用。这些结果为 PPTA 通过海马中的神经保护减轻脑缺血引起的记忆缺陷的能力提供了新的证据。PPTA 的神经保护作用似乎与其抗凋亡活性有关。PPTA 具有治疗缺血性中风的潜力。
