银杏酮酯(GBE50)抗心律失常作用研究

目的:观察银杏叶提取物银杏酮酯(GBE50)抗模型动物心律失常的药效并研究其机制.方法:采用乌头碱(Aco)、哇巴因(Oua)制作大鼠整体心律失常模型,体表心电记录;哇巴因和高钙诱发豚鼠右心室乳头肌迟后除极和触发活动,细胞内微电极记录.观察银杏酮酯对上述心律失常模型的影响.结果:8,16 mg·kg~(-1)GBE50 iv提高了哇巴因诱发室性早搏(VP)的阈剂量;16 mg·kg~(-1) GBE50提高了哇巴因诱发室性心动过速(VT)的阈剂量(P<0.05,P<0.01).GBE50能够提高乌头碱致心律失常的阈剂量:其中8 mg·kg~(-1) GBE50 iv能够提高乌头碱诱发VT的阈剂量,16 mg·kg~(-1) GBE50 iv能够提高乌头碱诱发的室性纤颤(VF)、心脏停搏(CA)的阈剂量,32 mg·kg~(-1) GBE50 iv能够提高乌头碱诱发VP,VT的阈剂量(P<0.05,P<0.01).银杏酮酯可以明显抑制哇巴因、高钙诱发的延迟后除极(DAD)和触发活动(TA),并呈一定的浓度依赖性.GBE50高、中、低各剂量组的DAD潜伏期的延长、DAD的幅值和时程及DAD下方的面积与对照组比均存在明显差别(P<0.01);TA发生率与对照组相比减少.结论:银杏酮酯增加了Aco,Oua造成的大鼠VP,VT,VF,CA的诱发剂量,且作用呈一定浓度依赖性.银杏酮酯延长了DAD的潜伏期,缩短了DAD的时程,减少了DAD的幅值,抑制了TA的发生,表明了银杏酮酯有抗心律失常作用,这一作用与抑制心律失常时异常的电活动过程有关.     

银杏叶提取物GBE50对实验性衰老大鼠海马CA1 区突触可塑性及学习记忆功能的影响

The content of total flavonoids in an extract of Ginkgo biloba,called GBE50,is 44% by weight.This is significantly greater than that in a standard extract of Ginkgo biloba,designated EGB761.To date,the mechanisms by which GBE50 and EGB761 function remain poorly understood.In the present study,an experimental rat model of aging was induced by intraperitoneal injection of D-galactose,followed by intragastric perfusion of GBE50 (30,60mg/kg),or EGB761 (60mg/kg).The water maze scores and hippocampal CA1 synaptic plasticity were evaluated.In the place navigation test,the GBE50 group rats did better than EGB761,while similar scores were obtained in the spatial probe test,and in the platform-switched test.In addition,long-term potentiation was significantly enhanced following high-frequency stimulation in the GBE50 and EGB761 groups,compared with the model group.These results demonstrate that GBE50 and EGB761 improved the learning and memory of aging rats.In particular,GBE50 administered at the 60mg/kg dose exhibited superior effects over EGB761 at the same 60mg/kg dose.Furthermore,the enhancement of hippocampal synaptic plasticity may be an underlying mechanism.     

银杏叶提取物抗四氯化碳诱导的大鼠肝纤维化的实验研究

目的:探讨银杏叶提取物(GBE)抑制NF-kappa Bp65的表达在四氧化碳(CCl4)诱导Wistar大鼠肝纤维化中肝细胞损伤的意义。方法:采用CCL4诱导的大鼠肝纤维化模型。生化检测各组血清丙氨酸氨基转移酶(ALT)、天氨酸氨基转移酶(AST)。采用免疫组化S-P方法检测肝细胞NF-kappa Bp65和ICAM-1表达并分析与肝细胞损害的关系。结果:治疗组大鼠的血清肝功能指标和肝纤维化病理分级与模型组比较都有显著的改善(P<0.05);治疗组大鼠肝组织细胞因子水平与模型组比较也显著降低(P<0.05)结论:银杏叶提取物可减轻肝组织的损伤及其纤维化程度,通过抑制NF-kappa Bp65的表达,进一步减弱了ICAM-1的表达,可能是其抗肝纤维化作用的靶点之一。     

Stimulation of DNA repair in Saccharomyces cerevisiae by Ginkgo biloba leaf extract

Many extracts prepared from plants traditionally used for medicinal applications contain a variety of phytochemicals with antioxidant and antigenotoxic activity. In this work we measured the DNA protective effect of extracts of Ginkgo biloba leaves from oxidative stress using Saccharomyces cerevisiae as experimental model. The extract improved viability of yeast cells under oxidative stress imposed by hydrogen peroxide. In accordance with previous reports on antioxidant properties of G. biloba extracts, pre-incubation of yeast cells promoted a decrease in intracellular oxidation. We assessed DNA damage by our recently developed yeast comet assay protocol. Upon oxidative shock, DNA damage decreased in a dose-dependent manner in experiments of pre-incubation and simultaneous incubation with the extract, indicating a direct protective effect. In addition, the extract improved DNA repair rate following oxidative shock as measured by faster disappearance of comet tails. This suggests that the extract stimulates the DNA repair machinery in its DNA protective action in addition to directly protect DNA from oxidation. The observed DNA repair depends on the DNA repair machinery since no DNA repair was observed under restrictive conditions in a conditional mutant of the CDC9 gene (Accession No. Z74212), encoding the DNA ligase involved in the final step of both nucleotide and base excision repair.     

Diffuse reticuloendothelial system involvement in type IV glycogen storage disease with a novel GBE1 mutation: a case report and review

Glycogen storage disease type IV is a rare autosomal recessive disorder of glycogen metabolism caused by mutations in the GBE1 gene that encodes the 1,4-alpha-glucan-branching enzyme 1. Its clinical presentation is variable, with the most common form presenting in early childhood with primary hepatic involvement. Histologic manifestations in glycogen storage disease type IV typically consist of intracytoplasmic non-membrane-bound inclusions containing abnormally branched glycogen (polyglucosan bodies) within hepatocytes and myocytes. We report a female infant with classic hepatic form of glycogen storage disease type IV who demonstrated diffuse reticuloendothelial system involvement with the spleen, bone marrow, and lymph nodes infiltrated by foamy histiocytes with intracytoplasmic polyglucosan deposits. Sequence analysis of the GBE1 gene revealed compound heterozygosity for a previously described frameshift mutation (c.1239delT) and a novel missense mutation (c.1279G>A) that is predicted to alter a conserved glycine residue. GBE enzyme analysis revealed no detectable activity. A review of the literature for glycogen storage disease type IV patients with characterized molecular defects and deficient enzyme activity reveals most GBE1 mutations to be missense mutations clustering in the catalytic enzyme domain. Individuals with the classic hepatic form of glycogen storage disease type IV tend to be compound heterozygotes for null and missense mutations. Although the extensive reticuloendothelial system involvement that was observed in our patient is not typical of glycogen storage disease type IV, it may be associated with severe enzymatic deficiency and a poor outcome.     

加用银杏叶片对氯氮平合并心得安治疗慢性精神分裂症的疗效和安全性的影响

目的 探讨银杏叶片对氯氮平合并心得安治疗慢性精神分裂症的疗效和安全性的影响.方法 将80例慢性精神分裂症病人随机分为研究组和对照组各40例,对照组给予抗精神病药物氯氮平、心得安治疗,研究组在此基础上,加用银杏叶片治疗,治疗12周.治疗前和治疗4、8、12周末分别用阳性与阴性症状量表(PANSS)评定临床疗效,用不良反应症状量表(TESS)评定不良反应,了解药物的安全性.结果 两组PANSS各因子评分比较差异无统计学意义(P＞0.05),但是阴性症状评分(P ＝0.053),有异质性和可比性,银杏叶片还可减少氯氮平的不良反应.结论 以阴性症状为主的精神分裂症在氯氮平合并心得安治疗过程中适合加用银杏叶片以增强疗效,减少不良反应.     

电针结合银杏酮酯对记忆障碍大鼠学习记忆及海马细胞因子的影响

目的:研究电针结合银杏酮酯(GBE 50)对D-半乳糖致衰老大鼠学习记忆障碍和海马细胞因子含量的影响,探索针药结合治疗对学习记忆改善作用的机制。方法:SD大鼠随机分成正常对照组、模型组、电针组、银杏酮酯组和针药结合组。采用腹腔注射D-半乳糖的方法建立记忆障碍衰老大鼠模型。电针组在造模第21天开始给予电针治疗,选用"百会"、双侧"足三里"穴位,隔天1次,治疗21 d;银杏酮酯组在造模第21天开始按150 mg/kg给予GBE 50灌胃,每天1次,持续21 d;针药结合组在给予D-半乳糖腹腔注射和GBE 50灌胃后给予电针治疗。治疗结束后采用Morris水迷宫观察大鼠行为学变化以及放射免疫分析方法检测各组大鼠海马白介素(IL)-1β、IL-6和肿瘤坏死因子(TNF)-α的含量。结果:模型组与正常对照组相比逃避潜伏期明显延长,游泳距离百分比明显减少(P<0.05,P<0.01);而电针组、银杏酮酯组和针药结合组与模型组相比,逃避潜伏期均显著缩短(P<0.05,P<0.01),游泳距离百分比明显增大(P<0.01),且针药结合组逃避潜伏期与电针组和银杏酮酯组相比差异有统计学意义(P<0.05)。模型组与正常对照组相比大鼠海马IL-1β和TNF-α含量增高,IL-6含量明显降低(P<0.05,P<0.01);与模型组比较,电针组、银杏酮酯组、针药结合组大鼠海马IL-1β含量均明显降低(P<0.05,P<0.01),银杏酮酯组和针药结合组IL-6含量均显著升高(P<0.01),电针组和针药结合组TNF-α含量明显下降(P<0.05)。结论:电针和GBE 50对大鼠海马IL-1β、IL-6和TNF-α含量均有不同程度的调节作用,抑制D-半乳糖引发的中枢神经系统免疫炎性反应;针药合用在改善学习记忆方面有一定的协同作用。     

多发性脑梗死痴呆大鼠行为学和生化学改变及CO-GBE的保护作用

目的: 探讨复方银杏滴丸(CO-GBE)对多发性脑梗死痴呆(MID)大鼠的保护作用. 方法: 采用向颈内动脉注入同种大鼠自体血栓的方法制成MID模型,测定模型大鼠的学习记忆能力和脑组织生化代谢. 结果: CO-GBE 10, 20, 40 mg/kg可以不同程度地增强模型大鼠的学习记忆能力,主要表现为在Morris水迷宫行为测试中,给药组大鼠逃避潜伏期和首次穿越平台的时间明显缩短(P<0.05, P<0.01). 与假手术组相比,模型组大鼠海马及皮质区乙酰胆碱酯酶活力明显降低,乳酸含量明显增加,CO-GBE可以不同程度地逆转这些异常变化. 结论: 改善胆碱能神经系统功能,抑制脑组织乳酸含量的增加,可能是CO-GBE增强学习记忆能力,保护脑组织,防治血管性痴呆的重要机制.     

从心肌力学观察银杏酮酯抗心肌缺血再灌注损伤的作用

目的研究银杏酮酯(GBE50)对大鼠离体心肌缺血再灌注(I/R)损伤的保护作用,并探讨心肌力学和血流动力学信息对其的评价作用。方法55只SD大鼠随机分为6组:模型组,GBE50低、中、高剂量组,丹参组,地尔硫卓组。进行Langendorff离体心脏灌流,各组均平衡灌注15 min,停灌造成全心缺血30 min,再复灌40 min。记录左心室内压力,观察药物对心脏心肌力学和血流动力学的影响。结果I/R后各组HR、mLVSP、DP、±dp/dt_(max)都明显低于缺血前,mLVDP、t-dp/dt_(max)明显升高(P0.05～0.001);随着再灌注时间的延长,各指标呈逐渐恢复的趋势。GBE50中剂量组、丹参组、地尔硫卓组DP、±dp/dt_(max)显著高于模型组(P0.05),t-dp/dt_(max)、mLVDP显著低于模型组(P0.05)。结论GBE50对心肌缺血再灌注损伤后心功能的下降具有明显的预防和保护作用,以心肌力学和血流动力学信息进行评价是稳定和可靠的。     

银杏酮酯预处理对心肌缺血再灌注大鼠心肌组织炎症相关细胞因子含量的影响

目的：探讨银杏酮酯（Ginkgo biloba extract 50,GBE50）预处理对大鼠心肌缺血再灌注损伤的保护作用及对炎症细胞因子和抗炎因子的影响。方法：58只SD大鼠分为假手术组,模型组,丹参组和低、中、高剂量GBE50组（n=8）。灌胃药物1周后,结扎冠状动脉左前降支30 min,再灌60 min建立大鼠心肌缺血再灌注模型。取心肌组织,HE染色观察心肌组织形态学变化,比色法检测心肌组织中髓过氧化物酶（myeloperoxidase,MPO）活性,放射免疫法检测心肌组织中肿瘤坏死因子α（tumor necrosis factor-α,TNF-α）、白细胞介素6（interleukin-6,IL-6）和IL-8含量,酶联免疫吸附测定法检测心肌组织中IL-4和IL-10含量。结果：与模型组相比,中剂量GBE50组心肌炎症反应减轻,心肌组织MPO活性明显降低（P〈0.01）;GBE50可明显减少心肌IL-6含量（P〈0.05,P〈0.01）,升高IL-4含量（P〈0.05,P〈0.01）。与模型组比较,GBE50组心肌组织中TNF-α含量降低,IL-10含量升高,但差异无统计学意义。结论：GBE50可降低缺血再灌注后心肌IL-6含量,升高IL-4含量,提示其可能通过抑制炎性细胞因子、促进抗炎因子的表达,对心肌缺血再灌注后的炎症反应发挥调控作用。