银杏叶提取物对心肌缺血再灌注微循环的保护作用

复制家兔缺血再灌注模型,采用显微电视和微机图像处理系统对20只家兔球结膜微血管口径、流速、流量等参数进行定量分析.结果:银杏叶提取物(GBE)组在结扎即刻、30分钟、再灌注30分钟等时相,与生理盐水组比较,微动脉、微静脉口径(3、4级)、微静脉流速、流量、毛细血管密度均增加,交换距离缩小(P<0.05).提示:GBE对心肌缺血再灌注微循环有显著的保护作用.其机制可能与扩张微血管口径、改善血流灌注有关.     

银杏叶注射液对实验性大鼠局灶性脑缺血的保护作用

以行为障碍、脑梗死范围、脑含水量、脑组织病理改变为观察指标,研究银杏叶注射液（ＧＢＥ）对大鼠大脑中动脉闭塞所致局部脑缺血的防治作用。结果表明,ＧＢＥ２０、４０ｍｇ／ｋｇ静脉注射可显著降低大鼠脑梗死范围和脑含水量,改善行为障碍。脑组织形态学检查显示,ＧＢＥ４０ｍｇ／ｋｇ组动物脑组织缺血病变较轻。提示ＧＢＥ对局灶性脑缺血具有保护作用。     

GBE1基因突变型糖原累积病Ⅳ型1例报告

目的探讨GBE1基因突变的糖原累积病Ⅳ型(GSD Ⅳ)患儿的临床特点及其家系的基因突变情况。方法分析1例GSD Ⅳ患儿的临床表现、肝脏病理结果及其父母的全外显子基因测序情况,并进行文献复习。结果患儿,男,1岁10个月,肝脾肿大6月余伴发热7天;肝脏组织病理示慢性肝损伤,不能除外遗传代谢病。全基因外显子检测示患儿存在2种新的GBE1基因的杂合突变,分别为来自父亲的c.1694GA杂合突变(致病性变异)和来自母亲的c.218AG杂合突变(疑似致病性变异)。结合患儿临床表现、病理及基因检测结果确诊为肝型GSD Ⅳ。结论新发现GEB 1基因c. 1694 GA的致病性杂合突变,丰富了GSD Ⅳ型在中国人群的突变谱。     

银杏叶提取物质量标准比较及标准提高思路探讨

银杏叶提取物(GBE)及其制剂在国内外广泛用于治疗心脑血管疾病。作者通过比较各国药典中GBE质量标准,对不同国家标准中的主要检测指标进行比较,并进一步与另一种GBE—银杏酮酯(GBE50)质量标准作对比分析。在此基础上,作者对GBE质量标准提高思路进行了探讨,目的为提高GBE的质量可控性,也为类似的天然药物提取物质量标准内容的选择提供参考。     

银杏叶制剂对正常脑温大鼠脑缺血治疗的实验研究

目的：观察常温下银杏叶提取物（GBF）对脑缺血组织抗氧化酶，脂质过氧化物及脑含水量的影响。方法：24只Wistar大鼠随机分为假手术组，脑缺血对照组及GBE治疗组（n=8)，制备正常脑温大鼠大脑中动脉缺血／再灌注模型，观察脑缺血组织超氧化物歧化酶（SOD），谷胱甘肽过氧化物酶（GSH－Px)，还原型谷胱甘肽（GSH），丙二醛（MDA）含量及脑含水量变化。结果：对照组SOD，GSH－Px,GSH水平低于手术组，治疗组高于对照组（P＜0．01或P＜0．05），对照组MDA水平高于假手术组，治疗组低于对照组（P＜0．01），对照组脑含水量高于假手术组，治疗组低于对照组（P＜0．01或P＜0．05），结论：正常脑温下，国产GBE能抑制脑缺血时自由基的过多产生和脂质过氧化反应，减轻脑水肿和血脑屏障破坏，保护脑缺血组织。     

Nickel-induced 1,4-alpha-glucan branching enzyme 1 up-regulation via the hypoxic signaling pathway

Using the mouse Affymetrix gene chip, we found that 1,4-alpha-glucan branching enzyme 1 (GBE1) was one of the most up-regulated genes following nickel exposure. This result was confirmed by Northern blot in two mouse cell lines, four mouse tissues, and three human cell lines. We further found that this gene was also up-regulated by cobalt, hypoxia, the iron chelator (deferoxamine, or DFO), and the prolyl hydroxylase (PH) inhibitor (dimethyloxalyglycine, DMOG), suggesting that hypoxia inducible factor-1alpha (HIF-1alpha) was involved in the up-regulation of this gene. Experiments using HIF-1alpha +/+ and HIF-1alpha -/- mouse cells demonstrated this gene was up-regulated through a HIF-1alpha-dependent hypoxic signaling pathway. Because the hypoxic signaling pathway is believed to be important in the initiation and progression of carcinogenesis, it is important to study genes regulated by this pathway.     

GBE50对大鼠生理/心理应激模型的应激缓解作用

目的 研究银杏叶提取物制剂GBE50的应激缓解作用.方法 应用大鼠生理/心理应激模型(PS/ES Model),大鼠分组后被安置在特制的二室电击笼中,经受足部电刺激(生理应激,PS)或旁观电击(心理应激,ES).每天10 min、为期6 d的刺激完成后,进行旷场试验测定行为学指标,其后测定大鼠血浆皮质酮水平和全血黏度数据.结果 GBE50可恢复PS组大鼠的活动性,显示有改善ES大鼠血液流变学的趋势,对PS/ES大鼠血浆皮质酮水平的影响似乎不大.结论 GBE50可从不同方面提供一定的应激缓解作用.     

Mechanism of Sclerostin/Lrp4 in the regulation of vascular smooth muscle cell calcification

Objective To investigate the possible mechanism of sclerostin/Lrp4 in calcification of VSMC induced by high phosphorus and the protective effect of Ginkgo biloba extract. Methods Aortic vascular smooth muscle cells (VSMCs) of SD rats were extracted and identified. VSMCs were divided into normal control group, high phosphorus induced calcification group (10 mmol/L β-glycerophosphate+50 μg/ml ascorbic acid), and high phosphorus induced calcification+Ginkgo biloba extract intervention group (10 mmol/L β-glycerophosphate+50 μg/ml ascorbic acid+0.5 mg/ml GBE), cultured in different mediums for 14 days. Vonkossa staining and alizarin red staining were used to detect the calcification of VSMCs. The mRNA level of BGP was detected by real time PCR, and the protein expressions of sclerostin and Lrp4 were detected by Western blot. Results Compared with normal control group, vonkossa staining and alizarin red staining showed significant calcium deposition in calcification group. Compared with calcification group, calcium salt deposition was significantly reduced in GBE treatment group. Real time PCR results showed β-catenin and BGP mRNA expressions in VSMC calcification group were higher than those in normal control group (P＜0.05). mRNA expressions of β-catenin and BGP in GBE treatment group were lower than those in calcification group (all P＜0.05). Compared with normal control group, the protein expression of sclerostin was increased, but the protein expression of Lrp4 was decreased in calcified group (all P＜0.05). Compared with calcification group, the protein expression of sclerostin decreased and the protein expression of Lrp4 increased in GBE treatment group (all P＜0.05). Conclusions High phosphorus can induce VSMC calcification by activating Wn/β-catenin signaling pathway. Sclerostin/Lrp4 is involved in hyperphosphine-induced VSMC calcification. GBE can reduce the high phosphorus induced VSMC calcification by regulating the Wnt/β-catenin signaling pathway.     

银杏酮酯口服自微乳化给药系统的制备

研究制备银杏酮酯口服自微乳化给药系统。采用平衡溶解度方法筛选乳化剂与助乳化剂; 采用伪三元相图法制备微乳; 采用正交法优化处方组成; 并考察自微乳化制剂的乳化效率、溶出度、稳定性与药动学研究等。结果表明, 由肉豆蔻酸异丙酯IPM、聚氧乙烯蓖麻油Cremophor EL、丙二醇与银杏酮酯组成的自微乳化给药系统遇水可自发形成粒径为20～50 nm的稳定微乳。自微乳化给药系统的乳化效率与溶出快, 且制剂稳定性高, 能提高生物利用度。制备的银杏酮酯口服自微乳化给药系统稳定有效。