钙/钙调蛋白依赖性蛋白激酶Ⅱγ在血液系统肿瘤中作用研究进展

血液系统恶性肿瘤是人类常见肿瘤疾病,发病率呈逐年上升趋势.钙/钙调蛋白依赖性蛋白激酶(calcium/calmodulin-dependent protein kinase,CaMK)是广泛表达的多功能丝氨酸/苏氨酸蛋白激酶,可调节不同类型细胞的发育及生理功能.造血细胞中CaMKⅡ的主要亚型CaMKⅡγ与多种血液系统肿...     

电针配合神经生长因子对脑缺血大鼠学习记忆能力的影响

目的观察电针配合外源性神经生长因子（NGF）对脑缺血大鼠学习记忆能力的影响。 方法将Sprague-Dawley大鼠40只按随机数字表分配法随机分为假手术组、模型组、NGF组、电针组和NGF+电针组,每组大鼠8只。模型组、NGF组、电针组和NGF+电针组用脑缺血-再灌注方法建立学习记忆障碍大鼠动物模型,4组大鼠血脑屏障稳定后,NGF组和NGF+电针组于尾静脉注射NGF（10 μg/kg体重,每日1次,连续15 d）,电针组和NGF+电针组同时进行电针治疗（取哑门、百会穴,频率100 Hz,输出电流2 mA,每日1次,每次20 min,连续15 d）,疗程结束后采用Morris水迷宫检测大鼠空间学习记忆能力的变化。 结果模型组、NGF组、电针组和NGF+电针组大鼠造模后均出现明显的学习记忆障碍,与假手术组比较差异有统计学意义（P<0.05）。各组治疗15 d后,NGF组、模型组和电针组之间,大鼠学习记忆能力无明显差异（P＞0.05）; NGF+电针组大鼠学习记忆能力明显提高,与模型组、电针组、NGF组比较,差异有统计学意义（P<0.01）。 结论电针配合神经生长因子对学习记忆障碍大鼠的学习能力具明显的改善作用。     

电针配合神经生长因子对脑缺血大鼠学习记忆能力的影响

Objective To observe the effect of nerve growth factor(NGF)and electro-acupuncture(EA) on learning and memory in rats with cerebral ischemia.Methods An experimental model of cerebral ischemiareperfusion was established in 40 rats,who were then randomly divided into a model group,a sham operated group,a NGF group,an acupuncture group and a NGF plus acupuncture group.Three weeks were allowed for the recovery of the blood-brain barrier lesion caused by ischemia-reperfusion before intravenous injection of NGF(10μg/kg,once daily for 15 days)via the vena caudalis.In the two acupuncture groups,this was administered in combination with EA at the Baihui(DU20)and Yamen(DU15)acupoints(frequency 100 Hz,2 mA,20 min/time,once daily for 15 days).Morris' water maze test was used to assess any changes in spatial learning and memory abilities.Results The ischemic rats showed significant learning and memory disorders compared with the sham-operated group.In the NGF group,the rats' learning and memory abilities did not impmve significantly compared with the model group and the EA group.Significantly better learning was observed in the NGF+EA group compared with the model group,the EA group and the NGF group.Conclusion NGF combined with EA can improve the learning and memory abilities of rats with learning and memory dysfunction caused by cerebral ischemia-repedusion.     

电针配合神经生长因子对脑缺血大鼠学习记忆能力的影响

Objective To observe the effect of nerve growth factor(NGF)and electro-acupuncture(EA) on learning and memory in rats with cerebral ischemia.Methods An experimental model of cerebral ischemiareperfusion was established in 40 rats,who were then randomly divided into a model group,a sham operated group,a NGF group,an acupuncture group and a NGF plus acupuncture group.Three weeks were allowed for the recovery of the blood-brain barrier lesion caused by ischemia-reperfusion before intravenous injection of NGF(10μg/kg,once daily for 15 days)via the vena caudalis.In the two acupuncture groups,this was administered in combination with EA at the Baihui(DU20)and Yamen(DU15)acupoints(frequency 100 Hz,2 mA,20 min/time,once daily for 15 days).Morris' water maze test was used to assess any changes in spatial learning and memory abilities.Results The ischemic rats showed significant learning and memory disorders compared with the sham-operated group.In the NGF group,the rats' learning and memory abilities did not impmve significantly compared with the model group and the EA group.Significantly better learning was observed in the NGF+EA group compared with the model group,the EA group and the NGF group.Conclusion NGF combined with EA can improve the learning and memory abilities of rats with learning and memory dysfunction caused by cerebral ischemia-repedusion.     

电针配合神经生长因子对脑缺血大鼠学习记忆能力的影响

Objective To observe the effect of nerve growth factor(NGF)and electro-acupuncture(EA) on learning and memory in rats with cerebral ischemia.Methods An experimental model of cerebral ischemiareperfusion was established in 40 rats,who were then randomly divided into a model group,a sham operated group,a NGF group,an acupuncture group and a NGF plus acupuncture group.Three weeks were allowed for the recovery of the blood-brain barrier lesion caused by ischemia-reperfusion before intravenous injection of NGF(10μg/kg,once daily for 15 days)via the vena caudalis.In the two acupuncture groups,this was administered in combination with EA at the Baihui(DU20)and Yamen(DU15)acupoints(frequency 100 Hz,2 mA,20 min/time,once daily for 15 days).Morris' water maze test was used to assess any changes in spatial learning and memory abilities.Results The ischemic rats showed significant learning and memory disorders compared with the sham-operated group.In the NGF group,the rats' learning and memory abilities did not impmve significantly compared with the model group and the EA group.Significantly better learning was observed in the NGF+EA group compared with the model group,the EA group and the NGF group.Conclusion NGF combined with EA can improve the learning and memory abilities of rats with learning and memory dysfunction caused by cerebral ischemia-repedusion.     

电针配合神经生长因子对脑缺血大鼠学习记忆能力的影响

Objective To observe the effect of nerve growth factor(NGF)and electro-acupuncture(EA) on learning and memory in rats with cerebral ischemia.Methods An experimental model of cerebral ischemiareperfusion was established in 40 rats,who were then randomly divided into a model group,a sham operated group,a NGF group,an acupuncture group and a NGF plus acupuncture group.Three weeks were allowed for the recovery of the blood-brain barrier lesion caused by ischemia-reperfusion before intravenous injection of NGF(10μg/kg,once daily for 15 days)via the vena caudalis.In the two acupuncture groups,this was administered in combination with EA at the Baihui(DU20)and Yamen(DU15)acupoints(frequency 100 Hz,2 mA,20 min/time,once daily for 15 days).Morris' water maze test was used to assess any changes in spatial learning and memory abilities.Results The ischemic rats showed significant learning and memory disorders compared with the sham-operated group.In the NGF group,the rats' learning and memory abilities did not impmve significantly compared with the model group and the EA group.Significantly better learning was observed in the NGF+EA group compared with the model group,the EA group and the NGF group.Conclusion NGF combined with EA can improve the learning and memory abilities of rats with learning and memory dysfunction caused by cerebral ischemia-repedusion.     

电针配合神经生长因子对脑缺血大鼠学习记忆能力的影响

Objective To observe the effect of nerve growth factor(NGF)and electro-acupuncture(EA) on learning and memory in rats with cerebral ischemia.Methods An experimental model of cerebral ischemiareperfusion was established in 40 rats,who were then randomly divided into a model group,a sham operated group,a NGF group,an acupuncture group and a NGF plus acupuncture group.Three weeks were allowed for the recovery of the blood-brain barrier lesion caused by ischemia-reperfusion before intravenous injection of NGF(10μg/kg,once daily for 15 days)via the vena caudalis.In the two acupuncture groups,this was administered in combination with EA at the Baihui(DU20)and Yamen(DU15)acupoints(frequency 100 Hz,2 mA,20 min/time,once daily for 15 days).Morris' water maze test was used to assess any changes in spatial learning and memory abilities.Results The ischemic rats showed significant learning and memory disorders compared with the sham-operated group.In the NGF group,the rats' learning and memory abilities did not impmve significantly compared with the model group and the EA group.Significantly better learning was observed in the NGF+EA group compared with the model group,the EA group and the NGF group.Conclusion NGF combined with EA can improve the learning and memory abilities of rats with learning and memory dysfunction caused by cerebral ischemia-repedusion.     

电针配合神经生长因子对脑缺血大鼠学习记忆能力的影响

Objective To observe the effect of nerve growth factor(NGF)and electro-acupuncture(EA) on learning and memory in rats with cerebral ischemia.Methods An experimental model of cerebral ischemiareperfusion was established in 40 rats,who were then randomly divided into a model group,a sham operated group,a NGF group,an acupuncture group and a NGF plus acupuncture group.Three weeks were allowed for the recovery of the blood-brain barrier lesion caused by ischemia-reperfusion before intravenous injection of NGF(10μg/kg,once daily for 15 days)via the vena caudalis.In the two acupuncture groups,this was administered in combination with EA at the Baihui(DU20)and Yamen(DU15)acupoints(frequency 100 Hz,2 mA,20 min/time,once daily for 15 days).Morris' water maze test was used to assess any changes in spatial learning and memory abilities.Results The ischemic rats showed significant learning and memory disorders compared with the sham-operated group.In the NGF group,the rats' learning and memory abilities did not impmve significantly compared with the model group and the EA group.Significantly better learning was observed in the NGF+EA group compared with the model group,the EA group and the NGF group.Conclusion NGF combined with EA can improve the learning and memory abilities of rats with learning and memory dysfunction caused by cerebral ischemia-repedusion.     

电针配合神经生长因子对脑缺血大鼠学习记忆能力的影响

Objective To observe the effect of nerve growth factor(NGF)and electro-acupuncture(EA) on learning and memory in rats with cerebral ischemia.Methods An experimental model of cerebral ischemiareperfusion was established in 40 rats,who were then randomly divided into a model group,a sham operated group,a NGF group,an acupuncture group and a NGF plus acupuncture group.Three weeks were allowed for the recovery of the blood-brain barrier lesion caused by ischemia-reperfusion before intravenous injection of NGF(10μg/kg,once daily for 15 days)via the vena caudalis.In the two acupuncture groups,this was administered in combination with EA at the Baihui(DU20)and Yamen(DU15)acupoints(frequency 100 Hz,2 mA,20 min/time,once daily for 15 days).Morris' water maze test was used to assess any changes in spatial learning and memory abilities.Results The ischemic rats showed significant learning and memory disorders compared with the sham-operated group.In the NGF group,the rats' learning and memory abilities did not impmve significantly compared with the model group and the EA group.Significantly better learning was observed in the NGF+EA group compared with the model group,the EA group and the NGF group.Conclusion NGF combined with EA can improve the learning and memory abilities of rats with learning and memory dysfunction caused by cerebral ischemia-repedusion.     

电针配合神经生长因子对脑缺血大鼠学习记忆能力的影响

Objective To observe the effect of nerve growth factor(NGF)and electro-acupuncture(EA) on learning and memory in rats with cerebral ischemia.Methods An experimental model of cerebral ischemiareperfusion was established in 40 rats,who were then randomly divided into a model group,a sham operated group,a NGF group,an acupuncture group and a NGF plus acupuncture group.Three weeks were allowed for the recovery of the blood-brain barrier lesion caused by ischemia-reperfusion before intravenous injection of NGF(10μg/kg,once daily for 15 days)via the vena caudalis.In the two acupuncture groups,this was administered in combination with EA at the Baihui(DU20)and Yamen(DU15)acupoints(frequency 100 Hz,2 mA,20 min/time,once daily for 15 days).Morris' water maze test was used to assess any changes in spatial learning and memory abilities.Results The ischemic rats showed significant learning and memory disorders compared with the sham-operated group.In the NGF group,the rats' learning and memory abilities did not impmve significantly compared with the model group and the EA group.Significantly better learning was observed in the NGF+EA group compared with the model group,the EA group and the NGF group.Conclusion NGF combined with EA can improve the learning and memory abilities of rats with learning and memory dysfunction caused by cerebral ischemia-repedusion.     

电针配合神经生长因子对脑缺血大鼠学习记忆能力的影响

Objective To observe the effect of nerve growth factor(NGF)and electro-acupuncture(EA) on learning and memory in rats with cerebral ischemia.Methods An experimental model of cerebral ischemiareperfusion was established in 40 rats,who were then randomly divided into a model group,a sham operated group,a NGF group,an acupuncture group and a NGF plus acupuncture group.Three weeks were allowed for the recovery of the blood-brain barrier lesion caused by ischemia-reperfusion before intravenous injection of NGF(10μg/kg,once daily for 15 days)via the vena caudalis.In the two acupuncture groups,this was administered in combination with EA at the Baihui(DU20)and Yamen(DU15)acupoints(frequency 100 Hz,2 mA,20 min/time,once daily for 15 days).Morris' water maze test was used to assess any changes in spatial learning and memory abilities.Results The ischemic rats showed significant learning and memory disorders compared with the sham-operated group.In the NGF group,the rats' learning and memory abilities did not impmve significantly compared with the model group and the EA group.Significantly better learning was observed in the NGF+EA group compared with the model group,the EA group and the NGF group.Conclusion NGF combined with EA can improve the learning and memory abilities of rats with learning and memory dysfunction caused by cerebral ischemia-repedusion.     

电针配合神经生长因子对脑缺血大鼠学习记忆能力的影响

Objective To observe the effect of nerve growth factor(NGF)and electro-acupuncture(EA) on learning and memory in rats with cerebral ischemia.Methods An experimental model of cerebral ischemiareperfusion was established in 40 rats,who were then randomly divided into a model group,a sham operated group,a NGF group,an acupuncture group and a NGF plus acupuncture group.Three weeks were allowed for the recovery of the blood-brain barrier lesion caused by ischemia-reperfusion before intravenous injection of NGF(10μg/kg,once daily for 15 days)via the vena caudalis.In the two acupuncture groups,this was administered in combination with EA at the Baihui(DU20)and Yamen(DU15)acupoints(frequency 100 Hz,2 mA,20 min/time,once daily for 15 days).Morris' water maze test was used to assess any changes in spatial learning and memory abilities.Results The ischemic rats showed significant learning and memory disorders compared with the sham-operated group.In the NGF group,the rats' learning and memory abilities did not impmve significantly compared with the model group and the EA group.Significantly better learning was observed in the NGF+EA group compared with the model group,the EA group and the NGF group.Conclusion NGF combined with EA can improve the learning and memory abilities of rats with learning and memory dysfunction caused by cerebral ischemia-repedusion.     

电针百会对APP/PS1转基因小鼠学习记忆能力及Tau蛋白磷酸化的影响

目的:基于Tau蛋白磷酸化探讨电针百会对APP/PS1转基因痴呆模型小鼠学习记忆能力的影响及其可能机制。方法:30只4月龄雌性APP/PS1转基因小鼠随机分为模型组、百会组和非穴组,10只同窝阴性野生小鼠为野生组;百会组电针百会穴,非穴组电针非穴,干预28d。采用Morris水迷宫实验观察小鼠学习记忆能力;尼氏染色观察小鼠海马神经元形态结构变化;蛋白免疫印记杂交技术(Western blot)检测小鼠海马组织在Ser-396位点上Tau蛋白磷酸化水平。结果:与模型组相比,百会组可改善小鼠的学习记忆能力(P0.05),减轻海马神经元形态结构的损伤,降低海马组织中Ser-396位点上Tau蛋白磷酸化水平(P0.05),非穴组与模型组相比无显著性差异(P0.05)。结论:电针百会能够改善APP/PS1转基因痴呆模型小鼠的学习记忆能力,其机制可能与抑制Tau蛋白磷酸化有关。     

电针对阿尔茨海默病大鼠学习记忆能力及前额叶P35/P25-周期蛋白依赖性激酶5-Tau蛋白磷酸化通路的影响

目的 观察电针百会、肾俞两穴对阿尔茨海默病(AD)模型大鼠学习记忆能力及前额叶皮质(PFC) P35/P25-周期蛋白依赖性激酶5 (CDK5)-Tau蛋白磷酸化信号通路的影响,以探讨电针治疗AD的相关机制。方法 雄性成年Sprague-Dawley大鼠随机分为正常对照组、假手术组、模型组和电针组,每组6只。后两组双侧海马注射Aβ_25-35,假手术组注射等量生理盐水。造模后次日,电针组电针百会、肾俞,留针15 min,每天1次,共10 d。治疗后,行Morris水迷宫实验,免疫组织化学染色和Western blotting检测各组PFC P35/P25-CDK5-Tau蛋白磷酸化相关蛋白的表达情况。结果 与正常对照组和假手术组比较,模型组的逃避潜伏期和搜索路径均增加(P < 0.05),穿越平台次数减少( P < 0.05);与模型组比较,电针组逃避潜伏期和搜索路径均缩短( P < 0.05),穿越平台次数增加( P < 0.05)。模型组P35/P25和CDK5阳性表达明显高于正常对照组和假手术组( P < 0.01),电针组显著低于模型组( P < 0.001)。模型组P35/P25、CDK5、Tau[pS199]、Tau[pS202]相对表达量高于正常对照组和假手术组( P < 0.05),电针组上述蛋白的表达低于模型组( P < 0.05)。 结论 电针刺激能有效改善AD大鼠的学习记忆和空间探索能力,可能通过影响大鼠PFC的P35/P25-CDK5-Tau蛋白磷酸化信号通路,延缓AD的发生与发展。     

钙/钙调素依赖性蛋白激酶Ⅱ及其抑制剂在细胞生长调控中的作用及机制

钙/钙调素依赖性蛋白激酶Ⅱ(calcium/calmodulin-dependent protein kinaseⅡ,Ca/CaMKⅡ)是钙/钙调节蛋白家族的一个主要成员,广泛分布于组织器官中,可通过调节G1/S期、G2/M期等有丝分裂节点调控细胞生长、增殖及分化的周期进程.近年来发现该分子活化可促进肿瘤发生和恶化,并与细胞耐药密切相关.CaMKⅡ抑制剂可通过抑制CaMKⅡ磷酸化,特异性抑制CaMKⅡ的活性,引起肿瘤细胞生长受抑或凋亡.对CaMK Ⅱ及其抑制剂的深入研究可有助于发现新的肿瘤靶向治疗途径.     

钙调蛋白依赖性蛋白激酶Ⅱ在维拉帕米逆转肺腺癌顺铂化疗耐药中的作用

目的探讨钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)在维拉帕米逆转肺腺癌顺铂化疗耐药中的作用。方法在肺腺癌细胞系(A549)中,采用CCK-8法检测维拉帕米逆转顺铂耐药的能力,采用流式细胞仪Annexin V-FITC/PI法检测维拉帕米逆转顺铂耐药中凋亡水平的效果,采用Western blotting检测逆转耐药过程中P-CaMKⅡ/CaMKⅡ蛋白表达水平的变化。结果在肺腺癌细胞系(A549)中,单药顺铂组、顺铂联合维拉帕米组的细胞增长抑制率分别为(55. 00±2. 60)%、(32. 30±1. 80)%,差异有统计学意义(P 0. 05)。凋亡实验表明,单药顺铂组细胞凋亡率为10. 30%,顺铂联合维拉帕米组为21. 60%,差异有统计学意义(P 0. 05)。Western blotting结果显示,在A549细胞中,顺铂联合维拉帕米组P-CaMKⅡ/Ca MKⅡ的表达明显低于单药顺铂组。结论在肺腺癌细胞中,CaMKⅡ参与维拉帕米逆转化疗耐药的过程。     

加味补阳还五汤对次声暴露下小鼠学习记忆能力的影响

目的观察加味补阳还五汤对16Hz(8Hz),130dB次声暴露下小鼠学习记忆能力的影响。方法将学习记忆能力相近的80只BALB/c小鼠分为16Hz组和8Hz组,其中每组再分为空白对照组、次声对照组以及次声加用药组(根据用药剂量的不同又分高、中、低剂量组),处理14d后测试其学习记忆能力的变化。结果次声对照组的学习记忆能力降低(P<0·05),16Hz用药组较次声对照组的逃逸时间明显缩短(P<0·01),8Hz用药组较次声对照组的逃逸时间无显著性差异,各剂量组之间未见显著性差异。结论16Hz(8Hz),130dB次声暴露14d(2h/d)可引起小鼠学习记忆能力的下降。加味补阳还五汤可以提高16Hz次声暴露后小鼠的学习记忆能力。     

长时间次声作用对大鼠学习记忆功能的影响

目的：通过观察长时间次声作用对大鼠学习记忆功能及隔内侧核(MS)和斜角带核(DB)超微结构的影响，探讨次声对大鼠学习记忆功能影响的机制。方法：16Hz，130dB次声作用SD大鼠2h／d，共42d，避暗回避实验观察大鼠学习记忆功能的改变，透射电镜观察大脑MS和DB超微结构的改变。结果：与对照组相比，实验组大鼠避暗回避实验错误次数明显增多，(2．9&;#177;1．9)次，对照组(0．8&;#177;0．8)次，潜伏期明显缩短，(153&;#177;22)s，对照组(290&;#177;15)s(t=3．61，P&;lt;0．01)。受损神经元的线粒体损伤，核糖体、糖原减少，溶酶体、脂褐素增多。结论：长时间次声作用可使隔—海马胆碱能通路神经元超微结构改变，并与大鼠学习记忆功能下降有关。     

次声对大鼠神经元细胞凋亡与Tau蛋白表达的影响

摘要 目的：探索声压级水平是8Hz、90dB的次声连续7d和14d暴露对大鼠海马区神经元细胞凋亡与Tau蛋白表达的影响。 方法：建立次声暴露模型。将24只SD大鼠平均分为对照组、1d组、7d组和14d组等四组。1d组次声暴露2h,7d组次声暴露7d每天2h,14d组次声暴露14d每天2h。对照组放置于无次声暴露仓内2h。运用TUNEL染色、Western Blot、ELISA等实验方法探索次声对大鼠海马区神经元细胞凋亡与Tau蛋白的影响。 结果：连续7d和14d的次声暴露组大鼠海马区神经元细胞凋亡增多,与对照组和1d组相比差异均有显著性意义且Tau蛋白表达也增多,与对照组和1d组相比差异也具有显著性意义,呈现随暴露时间的延长而增多的趋势。 结论：连续7d和14d次声暴露可能会导致大鼠神经功能损害。     

电针刺激对血管性痴呆大鼠学习记忆能力及大脑NO含量的影响

目的：观察电针刺激对血管性痴呆（VD）大鼠学习记忆能力及大脑氧化亚氮（NO）含量的影响。进一步讨论针灸治疗VD的机制,为临床推广和显示中医治疗VD的优势提供有力的实验依据。方法：实验中采取4-血管阻断法制备VD模型,用Morris水迷宫测定大鼠学习记忆能力,并用分光光度比色法测定其大脑中NO的含量。结果：模型大鼠表现明显的学习记忆障碍,在水迷宫实验中,其潜伏期显著延长,在原平台象限跨越平台次数与其余三个象限无显著差异;其大脑NO水平明显升高。而电针组潜伏期较模型组明显缩短,相同时间内跨越原平台次数明显多于其余三个象限;其大脑NO含量较模型组大鼠显著降低。结论：电针刺激能改善VD大鼠学习记忆能力,并能显著降低其大脑NO含量,具有逆转缺血性脑损伤后NO含量升高所致神经元损害过程,可能最终减少血管性痴呆的发生。