目的探讨右美托咪定调节血清磷脂酰肌醇-3-羟基酶(PI3K)/丝氨酸-苏氨酸蛋白激酶(AKT)信号通路对老年全身麻醉患者术后认知功能的影响。方法选取2021年2月至2022年2月在荆门市第二人民医院行全麻手术的老年患者82例进行前瞻性研究,采用...目的探讨右美托咪定调节血清磷脂酰肌醇-3-羟基酶(PI3K)/丝氨酸-苏氨酸蛋白激酶(AKT)信号通路对老年全身麻醉患者术后认知功能的影响。方法选取2021年2月至2022年2月在荆门市第二人民医院行全麻手术的老年患者82例进行前瞻性研究,采用抽签法将所有患者分为观察组和对照组,各41例。观察组在全身麻醉诱导开始10 min内静脉泵入右美托咪定,0.8μg/kg,随后以0.2~0.5μg·kg^(-1)·h^(-1)维持泵注;对照组静脉泵等量0.9%氯化钠溶液。观察并记录两组患者术前10 min、拔管前10 min、拔管后30 min的血流动力学指标;记录两组患者术中麻醉药用量及复苏情况。应用精神状态检查表(MMSE)记录患者术前、术后6 h、术后1 d、术后3 d MMSE评分,比较两组患者术前及术后即刻、术后1 d、术后3 d血清PI3K及AKT蛋白表达水平;通过Spearman秩相关分析检验PI3K、AKT与全身麻醉患者术后认知功能的相关性。结果与对照组比较,观察组拔管前10 min、拔管后30 min平均动脉压明显降低、心率明显减缓,差异均有统计学意义(P<0.05)。观察组术中使用丙泊酚及瑞芬太尼用量明显少于对照组,术后复苏各指标时间短于对照组,差异均有统计学意义(P<0.05)。观察组术后6 h MMSE评分低于术前,对照组术后6 h、术后1 d MMSE评分均低于术前,差异均有统计学意义(P<0.05);观察组术后6 h MMSE评分为(25.15±5.22)分,明显高于对照组[(21.57±3.58)分],差异有统计学意义(P<0.05)。术后即刻、术后1 d、术后3 d,两组PI3K、AKT水平均显著高于术前,观察组术后即刻、术后1 d、术后3 d PI3K、AKT水平均显著低于对照组,差异均有统计学意义(P<0.05)。经单因素相关分析,患者MMSE评分与血清PI3K、AKT水平呈负相关。结论右美托咪定可有效保护老年全身麻醉患者术后认知功能,其作用机制可能与PI3K/AKT信号通路有关。展开更多
目的:观察清络饮对佐剂关节炎大鼠环氧化酶-2(cyclooxygenase 2,COX-2)、磷脂酰肌醇3-激酶(phosphatidylinositol3-kinase,PI3K)、丝氨酸-苏氨酸蛋白激酶(serine/threonine protein kinase,AKT)的影响。方法:将大鼠随机分为4组,正常对...目的:观察清络饮对佐剂关节炎大鼠环氧化酶-2(cyclooxygenase 2,COX-2)、磷脂酰肌醇3-激酶(phosphatidylinositol3-kinase,PI3K)、丝氨酸-苏氨酸蛋白激酶(serine/threonine protein kinase,AKT)的影响。方法:将大鼠随机分为4组,正常对照组、模型对照组、雷公藤多苷片组、清络饮组,每组10只。除正常对照组外,其余3组每只大鼠右后足趾皮内注射弗氏完全佐剂0.1 m L,致炎第19天,清络饮组灌胃清络饮水溶液1.4 g·kg-1,雷公藤多苷片组灌胃雷公藤多苷片水溶液10 mg·kg-1,正常对照组和模型对照组灌胃等量的蒸馏水,每组大鼠连续给药30 d。实验结束后检测大鼠足肿胀率、关节炎指数;观察滑膜病理变化;采用酶联免疫吸附法检测大鼠白细胞介素-6(interleukin-6,IL-6)、IL-10、血管内皮生长因子(vascular endothelial growth factor,VEGF)、COX-2、PI3K、AKT指标水平。结果:1与正常对照组比较,模型对照组足肿胀率、关节炎指数数值明显升高,差异有统计学意义(P<0.01);与模型对照组相比,雷公藤多苷片组和清络饮组足肿胀率、关节炎指数明显下降,差异有统计学意义(P<0.01或P<0.05)。2模型对照组滑膜可见大量炎性细胞浸润,滑膜血管翳增多;滑膜组织增生,呈绒毛状突起至关节腔内;滑膜衬细胞分层增多、增厚;部分关节软骨表面毛糙或缺如。雷公藤多苷片组可见滑膜及其周围组织少量炎性细胞浸润,滑膜衬细胞增厚,关节面较模糊,部分关节软骨可见血管翳形成,关节面欠规整,部分关节软骨及软骨下骨破坏。3与正常对照组比较,模型对照组IL-6、VEGF、COX-2、PI3K、AKT数值明显升高,IL-10数值明显下降,差异具有统计学意义(P<0.01),与模型对照组比较,雷公藤多苷片组和清络饮组IL-6、VEGF、COX-2、PI3K、AKT数值明显下降,差异具有统计学意义异(P<0.01或P<0.05),IL-10数值明显升高,差异具有统计学意义(P<0.05)。结论:清络饮能够改善血管新生展开更多
The signaling mechanisms underlying ischemia-induced nerve cell apoptosis are poorly understood. We investigated the effects of apoptosis-related signal transduction pathways following ischemic spinal cord injury, inc...The signaling mechanisms underlying ischemia-induced nerve cell apoptosis are poorly understood. We investigated the effects of apoptosis-related signal transduction pathways following ischemic spinal cord injury, including extracellular signal-regulated kinase（ERK）, serine-threonine protein kinase（Akt） and c-Jun N-terminal kinase（JNK） signaling pathways. We established a rat model of acute spinal cord injury by inserting a catheter balloon in the left subclavian artery for 25 minutes. Rat models exhibited notable hindlimb dysfunction. Apoptotic cells were abundant in the anterior horn and central canal of the spinal cord. The number of apoptotic neurons was highest 48 hours post injury. The expression of phosphorylated Akt（pAkt） and phosphorylated ERK（p-ERK） increased immediately after reperfusion, peaked at 4 hours（p-Akt） or 2 hours（p-ERK）, decreased at 12 hours, and then increased at 24 hours. Phosphorylated JNK expression reduced after reperfusion, increased at 12 hours to near normal levels, and then showed a downward trend at 24 hours. Pearson linear correlation analysis also demonstrated that the number of apoptotic cells negatively correlated with p-Akt expression. These findings suggest that activation of Akt may be a key contributing factor in the delay of neuronal apoptosis after spinal cord ischemia, particularly at the stage of reperfusion, and thus may be a target for neuronal protection and reduction of neuronal apoptosis after spinal cord injury.展开更多
文摘目的探讨右美托咪定调节血清磷脂酰肌醇-3-羟基酶(PI3K)/丝氨酸-苏氨酸蛋白激酶(AKT)信号通路对老年全身麻醉患者术后认知功能的影响。方法选取2021年2月至2022年2月在荆门市第二人民医院行全麻手术的老年患者82例进行前瞻性研究,采用抽签法将所有患者分为观察组和对照组,各41例。观察组在全身麻醉诱导开始10 min内静脉泵入右美托咪定,0.8μg/kg,随后以0.2~0.5μg·kg^(-1)·h^(-1)维持泵注;对照组静脉泵等量0.9%氯化钠溶液。观察并记录两组患者术前10 min、拔管前10 min、拔管后30 min的血流动力学指标;记录两组患者术中麻醉药用量及复苏情况。应用精神状态检查表(MMSE)记录患者术前、术后6 h、术后1 d、术后3 d MMSE评分,比较两组患者术前及术后即刻、术后1 d、术后3 d血清PI3K及AKT蛋白表达水平;通过Spearman秩相关分析检验PI3K、AKT与全身麻醉患者术后认知功能的相关性。结果与对照组比较,观察组拔管前10 min、拔管后30 min平均动脉压明显降低、心率明显减缓,差异均有统计学意义(P<0.05)。观察组术中使用丙泊酚及瑞芬太尼用量明显少于对照组,术后复苏各指标时间短于对照组,差异均有统计学意义(P<0.05)。观察组术后6 h MMSE评分低于术前,对照组术后6 h、术后1 d MMSE评分均低于术前,差异均有统计学意义(P<0.05);观察组术后6 h MMSE评分为(25.15±5.22)分,明显高于对照组[(21.57±3.58)分],差异有统计学意义(P<0.05)。术后即刻、术后1 d、术后3 d,两组PI3K、AKT水平均显著高于术前,观察组术后即刻、术后1 d、术后3 d PI3K、AKT水平均显著低于对照组,差异均有统计学意义(P<0.05)。经单因素相关分析,患者MMSE评分与血清PI3K、AKT水平呈负相关。结论右美托咪定可有效保护老年全身麻醉患者术后认知功能,其作用机制可能与PI3K/AKT信号通路有关。
基金supported by the National Natural Science Foundation of ChinaNo.81271387+3 种基金the Research Special Fund of Public Welfare and Health Department of ChinaNo.201402009the National Key Technology R&D Program in ChinaNo.Z141107002514031
文摘The signaling mechanisms underlying ischemia-induced nerve cell apoptosis are poorly understood. We investigated the effects of apoptosis-related signal transduction pathways following ischemic spinal cord injury, including extracellular signal-regulated kinase（ERK）, serine-threonine protein kinase（Akt） and c-Jun N-terminal kinase（JNK） signaling pathways. We established a rat model of acute spinal cord injury by inserting a catheter balloon in the left subclavian artery for 25 minutes. Rat models exhibited notable hindlimb dysfunction. Apoptotic cells were abundant in the anterior horn and central canal of the spinal cord. The number of apoptotic neurons was highest 48 hours post injury. The expression of phosphorylated Akt（pAkt） and phosphorylated ERK（p-ERK） increased immediately after reperfusion, peaked at 4 hours（p-Akt） or 2 hours（p-ERK）, decreased at 12 hours, and then increased at 24 hours. Phosphorylated JNK expression reduced after reperfusion, increased at 12 hours to near normal levels, and then showed a downward trend at 24 hours. Pearson linear correlation analysis also demonstrated that the number of apoptotic cells negatively correlated with p-Akt expression. These findings suggest that activation of Akt may be a key contributing factor in the delay of neuronal apoptosis after spinal cord ischemia, particularly at the stage of reperfusion, and thus may be a target for neuronal protection and reduction of neuronal apoptosis after spinal cord injury.
