Although it has been more than 165 years since the first introduction of modern anesthesia to the clinic, there is surprisingly little understanding about the exact mechanisms by which general anesthetics induce uncon...Although it has been more than 165 years since the first introduction of modern anesthesia to the clinic, there is surprisingly little understanding about the exact mechanisms by which general anesthetics induce unconsciousness. As a result, we do not know how general anesthetics produce anesthesia at different levels. The main handicap to understanding the mechanisms of general anesthesia is the diversity of chemically unrelated compounds including diethyl ether and halogenated hydrocarbons, gases nitrous oxide, ketamine, propofol, benzodiazepines and etomidate, as well as alcohols and barbiturates. Does this imply that general anesthesia is caused by many different mechanisms? Until now, many receptors, molecular targets and neuronal transmission pathways have been shown to contribute to mechanisms of general anesthesia. Among these molecular targets, ion channels are the most likely candidates for general anesthesia, in particular γ-aminobutyric acid type A, potassium and sodium channels, as well as ion channels mediated by various neuronal transmitters like acetylcholine, amino acids amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid or N-methyl-D-aspartate. In addition, recent studies have demonstrated the involvement in general anesthesia of other ion channels with distinct gating properties suchas hyperpolarization-activated, cyclic- nucleotide-gated channels. The main aim of the present review is to summarize some aspects of current knowledge of the effects of general anesthetics on various ion channels.展开更多
Voltage-gated sodium （Nav） channels are indispensable membrane elements for the generation and propagation of electric signals in excitable cells. The successes in the crystallographic studies on prokaryotic Nay cha...Voltage-gated sodium （Nav） channels are indispensable membrane elements for the generation and propagation of electric signals in excitable cells. The successes in the crystallographic studies on prokaryotic Nay chan- nels in recent years greatly promote the mechanistic investigation of these proteins and their eukaryotic counterparts. In this paper, we mainly review the pro- gress in computational studies, especially the simula- tion studies, on these proteins in the past years.展开更多
目的探讨健康大鼠中耳黏膜中液体吸收速度和钠离子浓度的相关性。方法24只大鼠分成Ⅰ、Ⅱ、Ⅲ、Ⅳ组,每组6只,全身麻醉后分别在各组实验耳注入10、40、80、140 mM的NaCl溶液,对照耳注入140 mM NaCl溶液。30分钟后,中耳腔液体的体积开始...目的探讨健康大鼠中耳黏膜中液体吸收速度和钠离子浓度的相关性。方法24只大鼠分成Ⅰ、Ⅱ、Ⅲ、Ⅳ组,每组6只,全身麻醉后分别在各组实验耳注入10、40、80、140 mM的NaCl溶液,对照耳注入140 mM NaCl溶液。30分钟后,中耳腔液体的体积开始发生稳定变化,监测液体体积的变化,描记体积和时间变化曲线,通过线性回归计算液体吸收速率(K);吸收速率比(KR=K实验/K对照)定义为实验耳的吸收速率(K实验)与对照耳的吸收速率(K对照)的比值。结果Ⅰ、Ⅱ、Ⅲ、Ⅳ组的KR值分别为:0.5455±0.0685、0.6353±0.0579、0.7575±0.0611、0.9774±0.0585,差异有显著统计学意义(P<0.001);通过线性回归分析,KR值和钠离子浓度呈正相关性(r=0.9424,P<0.001)。结论本实验证实了活体动物中耳黏膜具有吸收功能,其吸收速度与钠离子的浓度呈正相关。展开更多
目的检测自发性高血压大鼠(SHR)和Wistar大鼠的ENaCs在mRNA水平的表达差异,探讨机械敏感性离子(Mechanosensitive Ion Channels,MS)对动脉压力感受器重调的作用。方法SHR大鼠和Wistar大鼠各6只,分别取左侧颈动脉窦、主动脉弓,异硫氰酸胍...目的检测自发性高血压大鼠(SHR)和Wistar大鼠的ENaCs在mRNA水平的表达差异,探讨机械敏感性离子(Mechanosensitive Ion Channels,MS)对动脉压力感受器重调的作用。方法SHR大鼠和Wistar大鼠各6只,分别取左侧颈动脉窦、主动脉弓,异硫氰酸胍-酚氯仿法抽提总RNA。采用荧光定量PCR法,分别测定αENaC、βENaC、γENaC在各组织的相对表达水平。结果正常血压的Wistar大鼠ENaCs表达在主动脉弓和颈动脉窦区域相对定量较SHR组大鼠高,在颈动脉窦区域表现更明显。结论高血压状态下,ENaCs在压力感受器区域下调表达,提示压力敏感性离子通道在压力反射重调方面可能发挥着一定作用。展开更多
目的探讨参松养心胶囊(SSYX)对心肌梗死后心律失常发生和心功能不全的影响及其作用机制。方法将40只新西兰大耳白兔行冠状动脉前降支结扎术后随机分为正常对照组(Control组)10只、心梗组(MI组)10只、心梗+胺碘酮组(MI+A组,0.4 g·kg...目的探讨参松养心胶囊(SSYX)对心肌梗死后心律失常发生和心功能不全的影响及其作用机制。方法将40只新西兰大耳白兔行冠状动脉前降支结扎术后随机分为正常对照组(Control组)10只、心梗组(MI组)10只、心梗+胺碘酮组(MI+A组,0.4 g·kg^(^(-1))·d^(^(-1)))10只、心梗+参松组(MI+S组,0.5 g·kg^(^(-1))·d^(^(-1)))10只。正常对照组开胸后在冠状动脉下穿线,但不结扎。术后,分别以普食、普食+胺碘酮粉末、普食+参松养心胶囊原粉喂食。8周后将家兔处死,在心梗周边区取材,检测各组白兔缝隙连接蛋白43(CX43)、钠钙交换体(NCX)和兰尼碱受体蛋白(Ry R2)m RNA的相对表达量。结果与Control组比较,MI组CX43、Ry R2 m RNA相对表达量显著下降(P<0.05),而NCX m RNA相对表达量虽然有所下降,但其差异无统计学意义(P>0.05);与MI组比较,MI+A组CX43、Ry R2 m RNA相对表达量显著升高(P<0.05),MI+S组CX43、NCX、Ry R2 m RNA的相对表达量也显著升高(P<0.05);与MI+A组比较,MI+S组CX43、NCX m RNA的相对表达量均显著升高(P<0.05)。结论参松养心胶囊可以改善心肌梗死后心律失常以及心功能不全,其机制可能与调控各钙离子通道的开放,抑制钙超载有关。展开更多
文摘Although it has been more than 165 years since the first introduction of modern anesthesia to the clinic, there is surprisingly little understanding about the exact mechanisms by which general anesthetics induce unconsciousness. As a result, we do not know how general anesthetics produce anesthesia at different levels. The main handicap to understanding the mechanisms of general anesthesia is the diversity of chemically unrelated compounds including diethyl ether and halogenated hydrocarbons, gases nitrous oxide, ketamine, propofol, benzodiazepines and etomidate, as well as alcohols and barbiturates. Does this imply that general anesthesia is caused by many different mechanisms? Until now, many receptors, molecular targets and neuronal transmission pathways have been shown to contribute to mechanisms of general anesthesia. Among these molecular targets, ion channels are the most likely candidates for general anesthesia, in particular γ-aminobutyric acid type A, potassium and sodium channels, as well as ion channels mediated by various neuronal transmitters like acetylcholine, amino acids amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid or N-methyl-D-aspartate. In addition, recent studies have demonstrated the involvement in general anesthesia of other ion channels with distinct gating properties suchas hyperpolarization-activated, cyclic- nucleotide-gated channels. The main aim of the present review is to summarize some aspects of current knowledge of the effects of general anesthetics on various ion channels.
基金We gratefully thank Mengdie Xia for her contribution in preparing the figures. This work was supported by the National Natural Science Foundation of China （Grant Nos. 31470033 and 31321062）.
文摘Voltage-gated sodium （Nav） channels are indispensable membrane elements for the generation and propagation of electric signals in excitable cells. The successes in the crystallographic studies on prokaryotic Nay chan- nels in recent years greatly promote the mechanistic investigation of these proteins and their eukaryotic counterparts. In this paper, we mainly review the pro- gress in computational studies, especially the simula- tion studies, on these proteins in the past years.
文摘目的探讨健康大鼠中耳黏膜中液体吸收速度和钠离子浓度的相关性。方法24只大鼠分成Ⅰ、Ⅱ、Ⅲ、Ⅳ组,每组6只,全身麻醉后分别在各组实验耳注入10、40、80、140 mM的NaCl溶液,对照耳注入140 mM NaCl溶液。30分钟后,中耳腔液体的体积开始发生稳定变化,监测液体体积的变化,描记体积和时间变化曲线,通过线性回归计算液体吸收速率(K);吸收速率比(KR=K实验/K对照)定义为实验耳的吸收速率(K实验)与对照耳的吸收速率(K对照)的比值。结果Ⅰ、Ⅱ、Ⅲ、Ⅳ组的KR值分别为:0.5455±0.0685、0.6353±0.0579、0.7575±0.0611、0.9774±0.0585,差异有显著统计学意义(P<0.001);通过线性回归分析,KR值和钠离子浓度呈正相关性(r=0.9424,P<0.001)。结论本实验证实了活体动物中耳黏膜具有吸收功能,其吸收速度与钠离子的浓度呈正相关。
文摘目的检测自发性高血压大鼠(SHR)和Wistar大鼠的ENaCs在mRNA水平的表达差异,探讨机械敏感性离子(Mechanosensitive Ion Channels,MS)对动脉压力感受器重调的作用。方法SHR大鼠和Wistar大鼠各6只,分别取左侧颈动脉窦、主动脉弓,异硫氰酸胍-酚氯仿法抽提总RNA。采用荧光定量PCR法,分别测定αENaC、βENaC、γENaC在各组织的相对表达水平。结果正常血压的Wistar大鼠ENaCs表达在主动脉弓和颈动脉窦区域相对定量较SHR组大鼠高,在颈动脉窦区域表现更明显。结论高血压状态下,ENaCs在压力感受器区域下调表达,提示压力敏感性离子通道在压力反射重调方面可能发挥着一定作用。
文摘目的探讨参松养心胶囊(SSYX)对心肌梗死后心律失常发生和心功能不全的影响及其作用机制。方法将40只新西兰大耳白兔行冠状动脉前降支结扎术后随机分为正常对照组(Control组)10只、心梗组(MI组)10只、心梗+胺碘酮组(MI+A组,0.4 g·kg^(^(-1))·d^(^(-1)))10只、心梗+参松组(MI+S组,0.5 g·kg^(^(-1))·d^(^(-1)))10只。正常对照组开胸后在冠状动脉下穿线,但不结扎。术后,分别以普食、普食+胺碘酮粉末、普食+参松养心胶囊原粉喂食。8周后将家兔处死,在心梗周边区取材,检测各组白兔缝隙连接蛋白43(CX43)、钠钙交换体(NCX)和兰尼碱受体蛋白(Ry R2)m RNA的相对表达量。结果与Control组比较,MI组CX43、Ry R2 m RNA相对表达量显著下降(P<0.05),而NCX m RNA相对表达量虽然有所下降,但其差异无统计学意义(P>0.05);与MI组比较,MI+A组CX43、Ry R2 m RNA相对表达量显著升高(P<0.05),MI+S组CX43、NCX、Ry R2 m RNA的相对表达量也显著升高(P<0.05);与MI+A组比较,MI+S组CX43、NCX m RNA的相对表达量均显著升高(P<0.05)。结论参松养心胶囊可以改善心肌梗死后心律失常以及心功能不全,其机制可能与调控各钙离子通道的开放,抑制钙超载有关。
