【Abstract】 Objective :To observe the clinical effect and security of gingko injection on treatment of unstable angina .Methods: one 192 patients with unstable angina pain were randomly divided into two groups. The treatment group was gave to routine treatment combined with gingko injection, and the control group was only gave to routine treatment. The symptoms and electrocardiogram of two groups were compared. Results: The effective rate of symptoms and electrocardiogram, the decrease rate of nitroglycerin in treatment group were 91.67%,66.67% and 89.58%,were all higher than of the control group. There was no adverse reaction, the function of liver and kidney was also no obvious change. Conclusion : The routine treatment combined with gingko injection had good effect in lysing the angina symptoms and improving the blood supply of coronary artery.
【Key words】Coronary Heart Disease Unstable Angina Gingko Injection
冠心病是一种常见疾病,在人类死亡的比例中占首位。流行病学研究显示,冠心病的发病率正呈逐年上升趋势。本文旨在观察银杏注射液对不稳定心绞痛患者的临床疗效及安全性。报告如下。
1 资料与方法
1.1 一般资料 192例患者均为2007年5月~2008年10月在我院心内科住院病例,均符合国际心脏病学会和协会及世界卫生组织临床命名标准化联合专题组《缺血性心脏病的命名及诊断标准》[1]。随机分为两组。治疗组96例,男性56例,女性40例;年龄49~74岁,平均年龄61.53岁;伴高血压病36例,糖尿病32例,高脂血症59例,吸烟38例,心律失常32例。对照组96例,男性54例,女性42例;年龄47~72岁,平均年龄60.27岁,伴高血压病28例,糖尿病35例,高血脂57例,心律失常37例。两组患者年龄、性别、病史、及合并症等差异无显著性(P>0.05),具有可比性。
1.2 治疗方法 两组均予硝酸酯、阿司匹林、低分子肝素及调脂等常规治疗,心绞痛发作时舌下含化硝酸甘油片。治疗组加用银杏注射液20ml兑入5%葡萄糖注射液或0.9%氯化钠注射液250ml静滴,每日一次。两组均治疗14天。
1.3 观察指标 用药期间记录心绞痛发作的情况及药物的不良反应;治疗前后常规检查12导联静息心电图并对比心电图变化,心绞痛发作时随时记录心电图,观察ST-T改变;治疗前后血、尿、小便常规及肝肾功能等检查。
1.4 疗效标准 参照1979年中西医结合治疗冠心病心绞痛及心律失常座谈会《冠心病心绞痛及心电图疗效评定标准》拟定。显效:轻度和中度心绞痛症状消失或基本消失,较重症状基本消失或减轻至“轻度”标准;心电图回复至“大致正常”或达到“正常心电图”。有效:轻度心绞痛发作次数、程度及持续时间有明显减轻,中度症状减轻至“轻度”标准,较重症状减轻至“中度”标准;心电图ST段治疗后回升0.05mV以上,但未达正常水平,在主要导联倒置T波改变变浅 (达25%以上者),或T波由平坦变为直立,房室或室内传导阻滞改善。无效:症状基本与治疗前相同; 心电图基本与治疗前相同。 硝酸甘油停减率分为停药(治疗后完全停用硝酸甘油)、 减量 (治疗后较治疗前硝酸甘油用量减少 50%以上)、不变 (治疗后硝酸甘油用量减少不足50%)。
1.5 统计学处理 计量资料以(面±S)表示,采用Ridit分析与 t 检验。
2 结果
2.1 两组心绞痛疗效比较 见表1,两组心绞痛疗效比较治疗组心绞痛疗效优于对照组(P<0.05)。
2.2 两组心电图疗效比较 见表 2 。 两组患者心 电图 疗效比较, 治疗组优于对照组(P<0.05) 。
2.3 两组速效扩冠药物停减情况比较 见表3。 结果示两组患者速效扩冠药物停减情况比较,治疗组停减率高于对照组(P <0.05) 。
2.4 两组治疗前后心绞痛发作次数 变化比较 见表 4 。结果示两组患者心绞痛发作次数治疗后均有改善 (P<0.01) 。
2.5 不良反应 治疗后患者的血常规、 尿常规、 便常规 、 肝功能、肾功能均无异常变化,未发现明显的不良反应。
Objective: To investigate the effects of Ginkgo biloba extract (EGb 761) on the morphology and function of retinal ganglion cells (RGC) in guinea pigs with optic nerve transection.
Methods: Seventyfive albino guinea pigs were randomly divided into five groups: normal control group, shamoperated group, untreated group, normal saline group and EGb 761 group. No operation was performed in the normal control group. Optic nerve was merely exposed in the shamoperated group, but transected at 1.0 mm from posterior pole of the eye ball in the untreated, normal saline and EGb 761 groups. Guinea pigs in the EGb 761 group or the normal saline group received daily intraperitoneal injection of EGb 761 (100 mg/kg) or corresponding volume of normal saline from 7 days before experiment to 28 days after experiment. Three guinea pigs in each group were sacrificed for apoptosis assay (TUNEL method) of RGC. Pattern electoretinograms (PERGs) were recorded 14 and 28 days after transection, respectively. At the end of the examination, six guinea pigs were killed for histological examination and RGC count.
Results: No TUNELpositive cells were observed in the normal control, shamoperated and EGb 761 groups, but there were TUNELpositive cells in the untreated group and the normal saline group. The numbers of RGCs in the untreated and normal saline groups were less than those in the normal control and shamoperated groups at 14 days or 28 days (P<0.05). Although the number of RGCs in the EGb 761 group was less than those in the normal control and shamoperated groups (P<0.05), it was more than those in the untreated and normal saline groups (P<0.05). N95 amplitude in EGb 761 group was higher than those in the untreated and normal saline groups (P<0.05) and close to those in the normal control and shamoperated groups (P>0.05) at 14 days or 28 days. The number of RGCs was positive correlated to N95 amplitude (r=0.859, P=0.001 5).
Conclusion: EGb 761 can inhibit the apoptosis of RGCs in guinea pigs after optic nerve transection, thus protect the morphology and function of RGCs.
1.2.1 实验动物分组 豚鼠使用严格遵循视觉与眼科研究协会(Association for Research in Vision and Ophthalmology, ARVO)有关视觉和眼科研究动物使用条款。所有豚鼠均在12 h明/12 h暗,温度为22~25 ℃,湿度为55%~60%的环境中饲养。采用计算机随机数字法将75只豚鼠分为5组:正常对照组、假手术组、模型组、模型+生理盐水组(生理盐水组)、模型+EGb 761组(EGb 761组),每组15只。每只鼠的右眼为实验眼,左眼为用于计算RGC存活指数的对照眼。
Figure 2 Effects of EGb 761 on retinal structure observed by HE staining (Light microscopy, ×400)
GCL: Ganglion cell layer; INL: Inner nuclear layer; ONL: Outer nuclear layer. A: Normal control group. There was no vascular structure in retina, and cubic RGCs arrayed regularly and the nerve fibers layer (NFL) of retina was thick. B: Shamoperated group. The number of RGCs was close to that in normal control group. C: Untreated group. The number of RGCs and the thickness of NFL were obviously less than those in normal control group. D: Normal saline group. RGCs were rare and NFL was very thin. E: EGb 761 group. The number of RGCs and the NFL were slightly less than those in normal control group. All cells white arrows pointed at were RGCs.
图3 视神经横断后14和28 d各组RGC存活指数(略)
Figure 3 Survival index of RGC in each group 14 and 28 days after optic nerve transection
A: Normal control group; B: Shamoperated group; C: Untreated group; D: Normal saline group; E: EGb 761 group. Data were represented as x±s, n=6. *P<0.05, vs normal control group; △P<0.05, vs shamoperated group; ▲P<0.05, vs untreated group; □P<0.05, vs normal saline group.
Figure 4 Changes of N95 amplitude in each group 14 and 28 days after optic nerve transection
A: Normal control group; B: Shamoperated group; C: Untreated group; D: Normal saline group; E: EGb 761 group. Data were represented as x±s, n=6. *P<0.05, vs normal control group; △P<0.05, vs shamoperated group; ▲P<0.05, vs untreated group; □P<0.05, vs normal saline group.
图5 视神经横断后28 d各组PERG波形(略)
Figure 5 PERG wave form in each group 28 days after optic nerve transection
N35: Negative wave 35; P50: Positive wave 50; N95: Negative wave 95. A: Normal control group; B: Shamoperated group; C: Untreated group; D: Normal saline group; E: EGb 761 group.
图6 N95振幅与RGC存活指数的相关关系(略)
Figure 6 Correlation of N95 amplitude with survival index of RGC
【参考文献】
1 Xie Z, Wu X, Gong Y, Song Y, Qiu Q, Li C. Intraperitoneal injection of Ginkgo biloba extract enhances antioxidation ability of retina and protects photoreceptors after lightinduced retinal damage in rats. Curr Eye Res. 2007; 32(5): 471479.
2 Chung HS, Harris A, Kristinsson JK, Ciulla TA, Kagemann C, Ritch R. Ginkgo biloba extract increases ocular blood flow velocity. J Ocul Pharmacol Ther. 1999; 15(3): 233240.
3 Chandrasekaran K, Mehrabian Z, Spinnewyn B, Chinopoulos C, Drieu K, Fiskum G. Neuroprotective effects of bilobalide, a component of Ginkgo biloba extract (EGb 761) in global brain ischemia and in excitotoxicityinduced neuronal death. Pharmacopsychiatry. 2003; 36(Suppl 1): S89S94.
4 Marcocci L, Packer L, DroyLefaix MT, Sekaki A, GardèsAlbert M. Antioxidant action of Ginkgo biloba extract EGb 761. Methods Enzymol. 1994; 234: 462475.
5 Nakazawa T, Tamai M, Mori N. Brainderived neurotrophic factor prevents axotomized retinal ganglion cell death through MAPK and PI3K signaling pathways. Invest Ophthalmol Vis Sci. 2002; 43(10): 33193326.
6 Ranchon I, Gorrand JM, Cluzel J, DroyLefaix MT, Doly M. Functional protection of photoreceptor from lightinduced damage by dimethylthiourea and Ginkgo biloba extract. Invest Ophthalmol Vis Sci. 1999; 40(6): 11911199.
7 Gong YY, Song Y, Xie ZG, Wu XW. Protective effect of Huangban Granule against lightinduced retinal damage in rats. J Chin Integr Med. 2008; 6(11): 11591163. Chinese with abstract in English.
8 Li Y, Schlamp CL, Nickell RW. Experimental induction of retinal ganglion cell death in adult mice. Invest Ophthalmol Vis Sci. 1999; 40(5): 10041008.
9 BenShlomo G, Bakalash S, Lambrou GN, Latour E, Dawson WW, Schwartz M, Ofri R. Pattern electroretinogram in a rat model of ocular hypertension: functional evidence for early detection of inner retinal damage. Exp Eye Res. 2005; 81(3): 340349.
10 Bach M, Hawlina M, Holder GE, Marmor MF, Meigen T, Vaegan, Mivake Y. Standard for pattern electroretinography. International Society for Clinical Electrophysiology of Vision. Doc Ophthalmol. 2000; 101(1): 1118.
11 Hirooka K, Tokuda M, Miyamoto O, Itano T, Baba T, Shiraga F. The Ginkgo biloba extract (EGb 761) provides a neuroprotective effect on retinal ganglion cells in a rat model of chronic glaucoma. Curr Eye Res. 2004; 28(3): 153157.
12 Holder GE. Significance of abnormal pattern electroretinography in anterior visual pathway dysfunction. Br J Ophthalmol. 1987; 71(3): 166171.
13 Viswanathan S, Frishman LJ, Robson JG. The uniform field and pattern ERG in macaques with experimental glaucoma. Invest Ophthalmol Vis Sci. 2000; 41(9): 27972810.
14 Mittag TW, Danias J, Pohorenec G, Yuan HM, Burakgazi E, ChalmersRedman R, Podos SM, Tatton WG. Retinal damage after 3 to 4 months of elevated intraocular pressure in a rat glaucoma model. Invest Ophthalmol Vis Sci. 2000; 41(11): 34513459.
15 Maffei L, Fiorentini A. Electroretinographic responses to alternating gratings before and after section of the optic nerve. Science. 1981; 211(4485): 953955.
16 Maffei L, Fiorentini A, Bisti S, Hollnder H. Pattern ERG in the monkey after section of the optic nerve. Exp. Brain Res. 1985; 59(2): 423425.
17 Holder GE. Pattern electroretinography (PERG) and an integrated approach to visual pathway diagnosis. Prog Retin Eye Res. 2001; 20(4): 531561.
18 Berardi N, Domenici L, Gravina A, Maffei L. Pattern ERG in rats following section of the optic nerve. Exp Brain Res. 1990; 79(3): 539546.
19 Berninger T, Schuurmans RP. Spatial tuning of the pattern ERG across temporal frequency. Doc Ophthalmol. 1985; 61(1): 1725.
20 Hood DC, Xu L, Thienprasiddhi P, Greenstein VC, Odel JG, Grippo TM, Liebmann JM, Ritch R. The pattern electroretinogram in glaucoma patients with confirmed visual field deficits. Invest Ophthalmol Vis Sci. 2005; 46(7): 24112418.