高效液相色谱法测定脑活素注射液中的氨基酸含量及肽图分析

本文采用高效液相色谱法分析研究了进口药品脑活素注射液中的氨基酸含量及其低分子肽的肽图。试验结果反映了该药品的内在质量,同时提出控制质量的可靠方法.     

Early postnatal treatment with peptide preparations influences spatial navigation of young and adult rats

The brain derived peptidergic drug Cerebrolysin has been found to support the survival of neurons in vitro and in vivo. Positive effects on learning and memory have been demonstrated in various animal models and also in clinical trials. In the present study the effects of early postnatal administration of Cerebrolysin (Cere, 10 mg/ml peptides) or an enriched peptide fraction of Cere (E021, 80.6 mg/ml peptides) were investigated in young, young adult, and old adult rats. Rat pups received the drugs or saline for control on postnatal days 1–7. The animals were tested in the Morris water maze (MWM) either in the 5th week, in the 3rd or the 16th month of life for 6 consecutive days (test days 1–6), eight trials per day. In order to prevent the chance finding of the hidden platform, the rigid underwater platform was replaced by a collapsible island, resting at the bottom of the pool. The platform was raised when the animal stayed in the target area for 2 s. In the young and young adult rats both Cere and E021 treated rats showed shorter escape latencies than saline treated controls on all 6 test days. No significant differences in the swimming speed were evaluated for the young rats, although in 3-month-old drug-tested animals a moderate increase of the swimming speed was investigated. For 16-month-old animals no significant differences in either escape latencies or swimming speed was found. Summarizing, early postnatal application of Cere or E021 improved the spatial learning and memory of young rats and led to long-lasting behavioural effects at least up to 3 months after treatment.     

脑精素注射液细菌内毒素检查法的研究

目的:建立脑精素注射液的细菌内毒素检查法。方法:根据中国药典2000年版二部收载的细菌内毒素检查法的要求进行实验。结果:将脑精素注射液稀释30倍,以标示灵敏度为0.5EU·mL~(-1)的鲎试剂检查是有效的。结论:鲎试验法取代家兔法对脑精素注射液进行热原检查是可行的。     

Cardioprotective effects of cerebrolysin on the lesion severity and inflammatory factors in a rat model of isoproterenol-induced myocardial injury

BackgroundMyocardial injury (MI) is an important heart condition and a major cause of morbidity and mortality worldwide. The current study was designed to investigate the cardioprotective effects of cerebrolysin (CLY) on the lesion severity and inflammatory factors in male rats using isoproterenol (ISO)-induced MI model.MethodsMI in rats was induced by injecting ISO (100 mg/kg) subcutaneously (sc) on the first 2 days. Then, CLY (5 ml/kg) was injected intraperitoneally (ip) post-treatment for 7 days. On the 3rd day, creatine phosphokinase (CK-MB) and cardiac troponin I (cTnI) levels in serum and, on the 10th day, the TNF-α and IL6 levels in serum and heart tissue were measured by enzyme-linked immunosorbent assay (ELISA). Finally, the heart of each rat was dissected out and stained for histopathological examination.ResultsOn the 3rd day, the serum CK-MB and cTnI levels in the ISO and CLY + ISO groups were significantly increased compared with that in the control and CLY + Sal groups. One week after the induction of MI, ISO administration showed a significant increase in the serum level of TNF-α in the ISO group compared with that in the control and CLY + Sal groups. Also, our findings showed only a moderate reduction in inflammatory cell infiltration and extent of edema following CLY treatment in the CLY + ISO group. Also, CLY induced vascular proliferation in the heart tissue.ConclusionsWe conclude that the severity of pathological changes induced by ISO in MI (e.g. inflammation and edema) can be limited by CLY treatment.     

新生儿缺氧缺血性脑病后续治疗观察研究

目的探讨新生儿期后丽珠赛乐、胞二磷胆碱和高压氧治疗中、重度新生儿缺氧缺血性脑病(HIE)的疗效及对预后的影响.方法62例中、重度缺氧缺血性脑病病人在新生儿早期严格按全国新生儿缺氧缺血性脑病协作组治疗方案治疗,满月后随机分三组:治疗1组丽珠赛乐5 ml/d,胞二磷胆碱0.125 g/d,静脉滴注,1次/d,连续10 d,每月1疗程,共3～5个疗程;治疗2组除上述治疗外,同时予高压氧治疗,每月10 d,共3～5疗程;对照组不予活脑药及高压氧治疗;所有病例定期随访1年,均给与指导喂养、早期干预,1岁时用0～6岁儿童神经心理量表进行智能评估.结果治疗2组发育商(98±8)＞治疗1组发育商(103±5)＞对照组(86±9),差异具有统计学意义(P＜0.05或P＜0.01).后遗症发生率治疗1组(8.33%)、治疗2组(7.69%)较对照组(50%)明显降低(P＜0.05).结论缺氧缺血性脑病新生儿期后丽珠赛乐、胞二磷胆碱和高压氧治疗可减少神经系统后遗症的发生,明显改善中、重度HIE的预后.     

Cerebrolysin in Alzheimer's disease: a randomized,double-blind,placebo-controlled trial with a neurotrophic agent

Summary. Summary. Cerebrolysin (Cere) is a compound with neurotrophic activity. It has been shown to be effective in the treatment of Alzheimer's disease (AD) in earlier trials. In this multicenter, randomized, double-blind, placebo-controlled, parallel-group study, patients were injected intravenously with placebo or 30 mL Cere five days per week for four weeks. Effects on cognition and global function were evaluated with the Alzheimer Disease Assessment Scale – Cognitive Subscale (ADAS-Cog) and the Clinicians Interview-based Impression of Change with Caregiver Input scale (CIBIC+) 4, 12, 24 weeks after the beginning of the injections. 192 patients were enrolled, 95 were randomized to placebo, and 97 to Cere. At baseline, there was a significant difference between groups for age, age of onset of dementia, and the number of patients with hallucinations. At week 12 there was a significant difference on the CIBIC+ (p = 0.033) in favor of Cere. The number of CIBIC+ responders (score ≤ 4), was significantly higher (p = 0.007), with 68 (76%) in the Cere group and 51 (57%) in the placebo group. Trends were noted in the Disability Assessment in Dementia scale and the Cornell Depression Scale. Adverse events were recorded in 73% of placebo and 64% of Cere patients. Most common adverse events were headaches, dizziness, weight loss and anxiety. Conclusions: Cere treatment was well tolerated and resulted in significant improvements in the global score two months after the end of active treatment. Received September 10, 2001; accepted November 15, 2001     

Amelioration of the cerebrovascular amyloidosis in a transgenic model of Alzheimer’s disease with the neurotrophic compound Cerebrolysin™

Summary. Increased production and reduced clearance of amyloid (A) plays a central role in the pathogenesis of Alzheimers disease (AD). We have recently shown that the neurotrophic peptide mixture Cerebrolysin (Cbl) has the ability of improving synaptic functioning and reducing amyloid deposition in a transgenic (tg) animal model of Alzheimers disease (AD). Since in AD, potentially toxic A aggregates accumulate not only around neurons but also in the blood vessels, then it is important to investigate whether bioactive compounds such as Cbl might have the capacity to ameliorate the age-related cerebral amyloid angiopathy (CAA) in tg models. To this end, tg mice expressing mutant human amyloid precursor protein (APP) under the Thy1 promoter were treated with Cbl or saline alone starting at 7 or 12 months of age for a total of three months. Neuropathological analysis with an antibody against A showed that Cbl decreased amyloid deposition around the blood vessels in a time dependant manner. These effects were accompanied by a reduction in perivascular microgliosis and astrogliosis and increased expression of markers of vascular fitness such as CD31 and ZO-1. No lymphocytic infiltration was observed associated with A in the vessels. Consistent with these findings, ultrastructural analysis showed that while in tg mice treated with saline alone there was an abundant accumulation of amyloid fibers in the vascular wall accompanied by thickening of the basal membrane and endothelial cell damage, in Cbl-treated mice there was considerable reduction in the subcellular alterations of endothelial and smooth muscle cells with preservation of basal membranes and intercellular junctions. Taken together, these results suggest that Cbl treatment might have beneficial effects in patients with cognitive impairment due to cerebrovascular amyloidosis by reducing A accumulation and promoting the preservation of the cerebrovasculature.     

Antiapoptotic effects of the peptidergic drug cerebrolysin on primary cultures of embryonic chick cortical neurons

Summary. Cerebrolysin (EBEWE Arzneimittel, Austria, Europe) is a widely used drug relieving the symptoms of a variety of neurological disorders, particularly of neurodegenerative dementia of the Alzheimer's type. It consists of approximately 25% of low molecular weight peptides (<10 k DA) and a mixture of approximately 75% free amino acids, this being based on the total nitrogen content. In this study we used a low serum (2% serum supplement) cell stress in-vitro model to assess drug effectiveness on neuronal viability and programmed cell death (PCD). In this in-vitro model the type of cell death was previously shown to be primarly apoptotic, which was verified by DNA-laddering and TUNEL-staining. For evaluation of neuronal viability a MTT-reduction assay was performed after 4 DIV and 8 DIV and the percentage of apoptotic neurons was determined by bis-benzimide staining of nuclear chromatin. To differentiate between possible effects of the free amino acids and the peptide fraction of Cerebrolysin an artificial amino acid mixture (AA-mix) was used as a control. Cerebrolysin, the AA-mix and 10% foetal calf serum (FCS) caused a similar increase in viability after 4 DIV, whereas the effects of the growth factors BDNF and FGF-2 were less pronounced. After 8 DIV Cerebrolysin, but not the AA-mix, was able to ameliorate neuronal viability, which could reflect a neuro-protective effect or an increased activity of the mitochondrial dehydrogenase measured in a MTT-reduction assay. The percentage of cells showing apoptotic chromatin changes was significantly reduced (p < 0.01) in cultures treated with Cerebrolysin, whereas the AA-mix failed to decrease the percentage of cells showing apoptotic chromatin changes. These findings ascertain an anti-apoptotic effect of the peptide fraction of Cerebrolysin and reveal a transient viability promoting effect of the amino acid fraction, which is most likely due to improved nutritional supply. Received June 7, 2000; accepted November 2, 2000     

施普善治疗缺血性卒中后早期恢复期疗效再评价

目的 :验证施普善治疗缺血性卒中后早期恢复期的疗效及安全性。方法 :多中心双盲随机平行对照研究 ,其中施普善组 199例 ,给予 10 0mL的氯化钠注射液 ,内含 30mL施普善 ;对照组 185例 ,给予氯化钠注射液 10 0mL ,均iv ,gtt,qd× 2 8d。结果 :治疗后施普善组智力检查量表评分比治疗前提高 3.3分±s 0 .6分 ,与对照组 (提高 2 .3分± 0 .7分 )比较差异有显著意义 (P <0 .0 5 )。治疗期间 2组病人的不良反应差异无显著意义 (P >0 .0 5 )。结论 :施普善对改善缺血性卒中后早期恢复阶段病人的认知功能有一定作用且有较好的安全性     

脑活素改善血管性痴呆患者智能状况的临床研究

目的:探索脑活素对血管性痴呆患者智能状况的改善效果。方法:将29例符合血管性痴呆标准的患者分为对照组和治疗组。对照组用血塞通0.4g,治疗组在对照组的基础上加用脑活素20mL,10d为1个疗程,3年共6个疗程,其后分别采用中文版简易智能状态检查(MMSE)量表进行积分,用中国人修订韦氏成人量表(WAIS-RC)进行智力测验比较。结果:根据WAIS-RC测验结果,两组3年后知识(11.32±1.76比9.23±1.78)、领悟(13.19±1.85比11.24±2.12)、算术(10.18±1.32比8.63±1.25)、相似(9.46±0.68比7.56±0.98)、数字广度(10.12±0.69比8.68±0.97)、词汇(31.25±0.78比27.32±1.02)、数字符号(31.35±1.20比25.35±0.78)、填图(9.78±0.98比7.45±0.65)、图片排列(19.16±0.74比15.23±1.52)等项目比较,治疗组积分明显高于对照组(t=1.96～5.21,P<0.05或0.01)。治疗组治疗前后上述项目自身对照积分亦有显著提高(t=1.96～5.21,P<0.05或0.01)。结论:脑活素能有效抑制神经细胞的凋亡,减少脑功能的受累,治疗血管性痴呆,对老年群体的康复有一定的治疗作用。