Background Isoflurane, a commonly used inhaled anesthetic, induces apoptosis in primary rat cortical neurons of rat in a concentration- and time-dependent manner by an unknown mechanism. We hypothesized that isofluran...Background Isoflurane, a commonly used inhaled anesthetic, induces apoptosis in primary rat cortical neurons of rat in a concentration- and time-dependent manner by an unknown mechanism. We hypothesized that isoflurane induced apoptosis by causing abnormal calcium release from the endoplasmic reticulum （ER） via activation of inositol 1,4,5-trisphosphate （IP3） receptors. Sevoflurane has a reduced ability to disrupt intracellular calcium homeostasis and is a less potent cytotoxic agent. This study examined and compared the cytotoxic effects of isoflurane and sevoflurane on rat primary cortical neurons and their relationship with disruption of intracellular calcium homeostasis and production of reactive oxygen species （ROS）.Methods Primary rat cortical neurons were treated with the equivalent of 1 minimal alveolar concentration （MAC） of isoflurane and sevoflurane for 12 hours. MTT reduction and LDH release assays were performed to evaluate cell viability. Changes of calcium concentration in the cytosolic space, [Ca^2＋]c, and production of ROS were determined after exposing primary rat cortical neurons to isoflurane and sevoflurane. We also determined the effects of IP3 receptor antagonist xestospongin C on isoflurane-induced cytotoxicity and calcium release from the ER in primary rat cortical neurons.Results -Isoflurane at 1 MAC for 12 hours induced cytotoxicity in primary rat corticai neurons, which was also associated with a high and fast elevation of peak [Ca^2＋]c. Xestospongin C significantly ameliorated isoflurane cytotoxicity in primary cortical neurons, as well as inhibited the calcium release from the ER in primary cortical neurons. Isoflurane did not induce significant changes of ROS production in primary rat cortical neurons. Sevoflurane, at equivalent exposure to isoflurane, did not induce similar cytotoxicity or elevation of peak [Ca^2＋]c in primary rat cortical neurons.Conclusion These results suggested that isoflurane induced elevation in [Ca^2＋]c, partially via elevated activit展开更多
目的比较不同异氟醚吸入麻醉方法对大鼠麻醉的安全性、稳定性及可操作性。方法将4月龄SD大鼠60只随机分为3组,分别通过吸入箱麻醉(A组)、不插管面罩麻醉(B组)、气管插管吸入麻醉(C组)5 h,进行吸入麻醉药浓度可控性、大鼠生命体征、术中...目的比较不同异氟醚吸入麻醉方法对大鼠麻醉的安全性、稳定性及可操作性。方法将4月龄SD大鼠60只随机分为3组,分别通过吸入箱麻醉(A组)、不插管面罩麻醉(B组)、气管插管吸入麻醉(C组)5 h,进行吸入麻醉药浓度可控性、大鼠生命体征、术中及术后死亡率比较。结果麻醉2 h A组大鼠死亡率为15%,处理结束时共死亡6只,并且麻醉箱内麻醉药气体浓度波动明显,目标浓度难以维持。B组与C组异氟醚吸入浓度恒定,维持平稳。B组麻醉3 h内未出现大鼠呼吸抑制及死亡,麻醉结束时死亡率为20%。处理结束后1 d C组死亡2只,术后7 d C组共死亡3只,A、B组无大鼠死亡,麻醉后死亡率C组高于A、B组。结论异氟醚面罩及气管插管吸入麻醉能保证准确、平稳的麻醉药吸入浓度;大鼠异氟醚吸入麻醉3 h内行面罩吸入是简便安全的,同时减少术后死亡率;长于3 h的吸入麻醉最好进行气管插管,但同时也会使术后死亡风险增高。展开更多
目的观察异氟醚对大鼠海马高级糖基化终末产物受体（receptor for advanced glycation end products，RAGE）表达及认知功能的影响。方法SD雄性老年大鼠（24月龄）45只，SD雄性成年大鼠（4月龄）45只，随机数字表法分为6组（n=15），老...目的观察异氟醚对大鼠海马高级糖基化终末产物受体（receptor for advanced glycation end products，RAGE）表达及认知功能的影响。方法SD雄性老年大鼠（24月龄）45只，SD雄性成年大鼠（4月龄）45只，随机数字表法分为6组（n=15），老年对照组（C1组），成年对照组（C2组）：吸入30％氧气的空氧混合气体对照；老年异氟醚单次吸入组（S1组），成年异氟醚单次吸入组（S2组）：1．5％异氟醚单次吸入2h；老年异氟醚多次吸入组（R1组），成年异氟醚多次吸入组（R2组）：1．5％异氟醚吸入3次，1次／d，2h／次。各组大鼠吸入处理后1d取8只行Morris水迷宫进行认知功能测试，其余大鼠处死取海马，RT—PCR方法测定RAGEmRNA水平，免疫组织化学方法测定RAGE蛋白表达。结果各组大鼠吸入处理过程中生命体征平稳，血氧饱和度及心率均在正常范围。C1组穿越平台次数为（7．30±2．40）次，探索时间为（49．90±6．22）S，S1、R1组与C1组相比穿越平台的次数减少[穿越平台次数分别为S1（3．90±2．42），R1（3．44±2．40），F=7．448，P〈0．01]，探索时间缩短[探索时间分别为S1（43．33±7．08）S，R1（39．09±4．56）S，F=7．63，P〈0．05]，而逃避潜伏期延长（P〈0．05）。R2组较C2组逃逸潜伏期延长[逃逸潜伏期分别为R2（14．65±3．83）S，C2（7．84±2．51）S，F=12．773，P〈0．01]，探索时间缩短（均P〈0．01），穿越平台次数减少（P〈0．01）。S2组与C2组比较，空间探索时间与穿越平台次数均未见显著统计学差异（P〉0．05）；RAGE表达：与C1组比较S1、R1组mRNA表达水平增高[mRNA表达分别为C1（0．11±0．02），S1（0．56±0．09），R1（0．73±0．14）F=169．447，P〈0．01]，免疫组化阳性细胞颗粒数增多（P〈0．01），S1组与R1组比较蛋白表达差异无统计学意义（P〉0．05）；与C2组比较，S2组mRNA水平及蛋展开更多
文摘Background Isoflurane, a commonly used inhaled anesthetic, induces apoptosis in primary rat cortical neurons of rat in a concentration- and time-dependent manner by an unknown mechanism. We hypothesized that isoflurane induced apoptosis by causing abnormal calcium release from the endoplasmic reticulum （ER） via activation of inositol 1,4,5-trisphosphate （IP3） receptors. Sevoflurane has a reduced ability to disrupt intracellular calcium homeostasis and is a less potent cytotoxic agent. This study examined and compared the cytotoxic effects of isoflurane and sevoflurane on rat primary cortical neurons and their relationship with disruption of intracellular calcium homeostasis and production of reactive oxygen species （ROS）.Methods Primary rat cortical neurons were treated with the equivalent of 1 minimal alveolar concentration （MAC） of isoflurane and sevoflurane for 12 hours. MTT reduction and LDH release assays were performed to evaluate cell viability. Changes of calcium concentration in the cytosolic space, [Ca^2＋]c, and production of ROS were determined after exposing primary rat cortical neurons to isoflurane and sevoflurane. We also determined the effects of IP3 receptor antagonist xestospongin C on isoflurane-induced cytotoxicity and calcium release from the ER in primary rat cortical neurons.Results -Isoflurane at 1 MAC for 12 hours induced cytotoxicity in primary rat corticai neurons, which was also associated with a high and fast elevation of peak [Ca^2＋]c. Xestospongin C significantly ameliorated isoflurane cytotoxicity in primary cortical neurons, as well as inhibited the calcium release from the ER in primary cortical neurons. Isoflurane did not induce significant changes of ROS production in primary rat cortical neurons. Sevoflurane, at equivalent exposure to isoflurane, did not induce similar cytotoxicity or elevation of peak [Ca^2＋]c in primary rat cortical neurons.Conclusion These results suggested that isoflurane induced elevation in [Ca^2＋]c, partially via elevated activit
文摘目的比较不同异氟醚吸入麻醉方法对大鼠麻醉的安全性、稳定性及可操作性。方法将4月龄SD大鼠60只随机分为3组,分别通过吸入箱麻醉(A组)、不插管面罩麻醉(B组)、气管插管吸入麻醉(C组)5 h,进行吸入麻醉药浓度可控性、大鼠生命体征、术中及术后死亡率比较。结果麻醉2 h A组大鼠死亡率为15%,处理结束时共死亡6只,并且麻醉箱内麻醉药气体浓度波动明显,目标浓度难以维持。B组与C组异氟醚吸入浓度恒定,维持平稳。B组麻醉3 h内未出现大鼠呼吸抑制及死亡,麻醉结束时死亡率为20%。处理结束后1 d C组死亡2只,术后7 d C组共死亡3只,A、B组无大鼠死亡,麻醉后死亡率C组高于A、B组。结论异氟醚面罩及气管插管吸入麻醉能保证准确、平稳的麻醉药吸入浓度;大鼠异氟醚吸入麻醉3 h内行面罩吸入是简便安全的,同时减少术后死亡率;长于3 h的吸入麻醉最好进行气管插管,但同时也会使术后死亡风险增高。
文摘目的观察异氟醚对大鼠海马高级糖基化终末产物受体（receptor for advanced glycation end products，RAGE）表达及认知功能的影响。方法SD雄性老年大鼠（24月龄）45只，SD雄性成年大鼠（4月龄）45只，随机数字表法分为6组（n=15），老年对照组（C1组），成年对照组（C2组）：吸入30％氧气的空氧混合气体对照；老年异氟醚单次吸入组（S1组），成年异氟醚单次吸入组（S2组）：1．5％异氟醚单次吸入2h；老年异氟醚多次吸入组（R1组），成年异氟醚多次吸入组（R2组）：1．5％异氟醚吸入3次，1次／d，2h／次。各组大鼠吸入处理后1d取8只行Morris水迷宫进行认知功能测试，其余大鼠处死取海马，RT—PCR方法测定RAGEmRNA水平，免疫组织化学方法测定RAGE蛋白表达。结果各组大鼠吸入处理过程中生命体征平稳，血氧饱和度及心率均在正常范围。C1组穿越平台次数为（7．30±2．40）次，探索时间为（49．90±6．22）S，S1、R1组与C1组相比穿越平台的次数减少[穿越平台次数分别为S1（3．90±2．42），R1（3．44±2．40），F=7．448，P〈0．01]，探索时间缩短[探索时间分别为S1（43．33±7．08）S，R1（39．09±4．56）S，F=7．63，P〈0．05]，而逃避潜伏期延长（P〈0．05）。R2组较C2组逃逸潜伏期延长[逃逸潜伏期分别为R2（14．65±3．83）S，C2（7．84±2．51）S，F=12．773，P〈0．01]，探索时间缩短（均P〈0．01），穿越平台次数减少（P〈0．01）。S2组与C2组比较，空间探索时间与穿越平台次数均未见显著统计学差异（P〉0．05）；RAGE表达：与C1组比较S1、R1组mRNA表达水平增高[mRNA表达分别为C1（0．11±0．02），S1（0．56±0．09），R1（0．73±0．14）F=169．447，P〈0．01]，免疫组化阳性细胞颗粒数增多（P〈0．01），S1组与R1组比较蛋白表达差异无统计学意义（P〉0．05）；与C2组比较，S2组mRNA水平及蛋
