PD149163 induces hypothermia to protect against brain injury in acute cerebral ischemic rats
PD149163 induces hypothermia to protect against brain injury in acute cerebral ischemic rats
复制标题
PD149163诱导低温保护急性脑缺血大鼠脑损伤
DOI：
10.1016/j.jphs.2017.10.004
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发表时间：
2017-11-01
影响因子：
3.5
通讯作者：
Sun, Xiu-Lan
中科院分区：
文献类型：
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作者：
Xue, Teng-Fei;Ding, Xu;Sun, Xiu-Lan
通过物理或药理学方法治疗性低温是治疗急性脑缺血的一种很有前途的策略。在本研究中，我们通过腹腔注射PD149163对Sprague Dawley大鼠进行低温诱导。我们发现PD149163治疗可引起轻度低温，但局部脑血流量（LCBF）未发生改变。为评价PD149163的神经保护作用，本研究采用TTC染色、HE染色和尼氏染色。我们发现PD149163能预防缺血引起的神经元损伤，抑制神经胶质细胞的增殖和活化。同时，我们观察到PD149163改善了凋亡，其特征是下调caspase-3和Bax，但上调Bcl-2。此外，PD149163显著降低JNK和AMPK/mTOR信号通路的激活，从而通过增加P62的表达，降低LC3-II / LC3-I的比例和Beclin的表达来抑制自噬。综上所述，本研究结果揭示了pd149163诱导的低体温对脑缺血的治疗作用，并为脑卒中治疗提供了新的策略。(c) 2017年作者。由Elsevier B.V.代表日本药理学会制作和主办。
Therapeutic hypothermia is a promising strategy for acute cerebral ischemia via physical or pharmacological methods. In this study, we pharmacologically induced hypothermia on Sprague Dawley rats by intraperitoneally injecting PD149163. We found that mild hypothermia was induced by PD149163 treatment without local cerebral blood flow (LCBF) alteration. To evaluate the neuroprotective effects of PD149163, TTC staining, HE staining and Nissl's staining were performed in our study. We found that PD149163 could prevent neuronal damage, and inhibit proliferation and activation of glial cells induced by ischemia. Simultaneously, we observed PD149163 ameliorated apoptosis characterized by downregulated caspase-3 and Bax, but elevated Bcl-2. Moreover, PD149163 dramatically reduced JNK and AMPK/mTOR signaling pathway activation, and thereby inhibited autophagy by increased P62 expression, decreased the ratio of LC3-II to LC3-I and the expression of Beclin. Taken together, the present findings reveal the therapeutic effects of PD149163-induced hypothermia in brain ischemia, and provide a new strategy for stroke treatment. (c) 2017 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.