Effects of calpain on sevoflurane-induced aged rats hippocampal neuronal apoptosis
Effects of calpain on sevoflurane-induced aged rats hippocampal neuronal apoptosis
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DOI：
10.1007/s40520-015-0466-5
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发表时间：
2016-08-01
影响因子：
4
通讯作者：
Wang, Qiujun
中科院分区：
文献类型：
--
作者：
Liu, Xiang;Song, Xueyin;Wang, Qiujun
背景七氟醚是最常用的挥发性麻醉药之一，它已被证明可诱导老年大鼠广泛的神经细胞凋亡变性。钙蛋白酶在几种类型的细胞凋亡过程中也被激活。方法将72只18月龄雄性SD大鼠随机分为3组（n = 24）：对照组（n = 24），单纯暴露于含氮量为50%O2的湿空气中3 h; M组于吸入3%七氟醚前30 min尾静脉注射钙蛋白酶抑制剂10 mg/kg，随后给予MDL 28170 3.33 mg/kg/h，持续3 h。Sev组大鼠仅暴露于3%七氟醚3 h，不使用钙蛋白酶抑制剂。采用Morris水迷宫测试学习记忆能力。用流式细胞仪测定胞浆钙浓度。用荧光团或生物素标记的Annexin-V可以通过与PS结合来识别凋亡细胞。结果与Sev组相比，M组大鼠潜伏期短，穿越前一平台点的次数多。结论七氟醚可能通过增加细胞内[Ca 2 +]c和mu-calpain活性诱导细胞凋亡，这可能是七氟醚诱导细胞凋亡的分子机制之一。
Background Sevoflurane is one of the most commonly used volatile anesthetics and it has been shown to induce widespread apoptotic neurodegeneration in aged rat. Calpain is also activated during apoptosis in several types of cells. We hypothesized that calpain resulted in apoptosis under long time sevoflurane exposure, and it might play a role in the sevoflurane-induced memory impairment in aged rats.Methods Seventy-two 18-month-old male Sprague-Dawley rats were randomly divided into three groups (n = 24): Control group rats were exposed to simply humid 50 % O-2 balanced by N-2 for 3 h; While M group rats received calpain inhibitor 10 mg/kg via the tail vein intravenously at 30 min before the animals inhaled 3 % sevoflurane for 3 h, subsequently received MDL 28170 3.33 mg/kg/h for 3 h. Sev group rats were only exposed to 3 % sevoflurane for 3 h without calpain inhibitor. Morris Water Maze was used to test the ability of learning and memory. Cytosolic calcium concentration was measured by using flow cytometry. Annexin-V labeled with a fluorophore or biotin can identify apoptotic cells by binding to PS. The expression of calpain in the hippocampus of rats was tested by Western blots.Results The results showed that the M group had a shorter latency and had a larger number of times crossing over the previous platform site than that of the Sev group. Compared with Sev group, apoptosis rate and 76/80 kDa ratio of mu-calpain were significantly decreased in M group on the 1st day.Conclusions Sevoflurane might induce apoptosis through increasing [Ca2+]c and the activity of mu-calpain, which might be identified at least partially the molecular mechanism by which sevoflurane induces apoptosis.