松龄血脉康对大鼠局灶性脑缺血-再灌注损伤和细胞凋亡的影响

目的探讨松龄血脉康对局灶性脑缺血-再灌注损伤和细胞凋亡的作用及机制。方法线栓法制作大鼠大脑中动脉阻塞(MCAO)模型。观察松龄血脉康对脑缺血-再灌注损伤大鼠行为学、海马CA1区凋亡细胞数、细胞超微结构的影响;运用免疫组织化学法检测海马凋亡相关基因Bcl-2、Bax蛋白免疫反应阳性细胞表达。结果松龄血脉康显著降低MCAO模型大鼠神经功能缺损评分,明显减少海马组织凋亡细胞数,促进海马神经元修复,松龄血脉康组海马Bcl-2的表达明显增加、Bax的表达降低。结论松龄血脉康可减少脑缺血-再灌注损伤后神经元的凋亡而发挥脑保护作用,机制可能与增强Bcl-2的表达及抑制Bax的表达有关。     

Protective effect of compound Danshen (Salvia miltiorrhiza) dripping pills alone and in combination with carbamazepine on kainic acid-induced temporal lobe epilepsy and cognitive impairment in rats

Context: Temporal lobe epilepsy (TLE) is resistant to antiepileptic drugs (AEDs) and is associated with cognitive impairment. The modern Chinese medicine, compound Danshen dripping pills (CDDP), is clinically effective in treating epilepsy and improving cognitive impairment.

Objective: This study evaluated the protective effects of CDDP alone and in combination with carbamazepine (CBZ) on kainic acid-induced TLE and cognitive impairment in rats.

Materials and methods: Sprague–Dawley rats were randomly divided into five groups: control (sham operated), model, CDDP, CBZ and combined. A TLE model was then created via bilateral intrahippocampal injection of 0.35?μg kainic acid (KA). Rats received CDDP (85?mg/kg), CBZ (100?mg/kg) or combined (85?mg/kg CDDP +100?mg/kg CBZ) via intragastric administration for 90?d, respectively. Seizure intensity, apoptosis and glial cell line-derived neurotrophic factor (GDNF) were measured. Furthermore, the improvement in cognitive impairment and hippocampal neuronal damage was evaluated.

Results: CDDP combined with CBZ significantly decreased seizure severity and frequency (p?p?p?p?p?Conclusion: These findings support the use of CDDP as an adjuvant drug for the treatment of TLE and cognitive deficit. Its mechanism might be related to an anti-apoptosis effect and up-regulation of GDNF.     

Montelukast potentiates the protective effect of rofecoxib against kainic acid-induced cognitive dysfunction in rats

There is an evolving consensus that mild cognitive impairment (MCI) serves as a prodrome to Alzheimer's disease. Antioxidants and COX-2 (cyclo-oxygenase-2) inhibitors have also been reported to have beneficial effects against conditions of memory impairment. Newer drugs like cysteinyl leukotriene inhibitors have shown neuroprotective effect in animal models of ischemia. Thus, the present study purports to explore the potential role of montelukast (a cysteinyl leukotriene inhibitor) in concert with rofecoxib (COX-2 inhibitor) and caffeic acid (a 5-LOX inhibitor and potent antioxidant) against kainic acid induced cognitive dysfunction in rats. In the experimental protocol, kainic acid (0.4 μg/2 μl) in artificial cerebrospinal fluid (ACSF) was given intrahippocampally (CA3 region) to induce a condition similar to MCI. Memory performance was measured on days 10-14 and the locomotor activity was measured on days 1, 7 and 14. For estimation of biochemical, mitochondrial and histopathological parameters, animals were sacrificed on day 14, stored at − 80 °C and the estimation was done on the 15th day. The treatment groups consisting of montelukast (0.5 and 1 mg/kg), rofecoxib (5 and 10 mg/kg) and caffeic acid (5 and 10 mg/kg) showed significant improvement in memory performance, oxidative stress parameters and mitochondrial function as compared to that of control (kainic acid treated), however, combination of montelukast with rofecoxib showed significant improvement in their protective effect. Thus the present study emphasizes the positive modulation of cysteinyl leukotriene receptor inhibition on COX (cyclooxygenase) and LOX (lipoxygenase) pathways in the control of the neuroinflammation in kainic acid induced cognitive dysfunction in rats.     

Pharmacokinetic and pharmacodynamic interactions of valproate, phenytoin, phenobarbitone and carbamazepine with curcumin in experimental models of epilepsy in rats

The present study investigates the interaction of curcumin with four antiepileptic drugs (AEDs) in male Wistar rats. In the first protocol, seizures were induced using pentylenetetrazole (PTZ) and valproate was injected intraperitoneally (i.p.) in therapeutic and sub-therapeutic doses 30 min before PTZ administration. Curcumin was co-administered with sub-therapeutic dose of valproate 60 min before PTZ injection. In the second protocol, seizures were induced by maximal-electroshock. Phenytoin, phenobarbitone and carbamazepine were injected in their therapeutic and sub-therapeutic doses 120, 60 and 30 min, respectively, before seizure induction. Curcumin was administered along with sub-therapeutic doses of phenytoin, phenobarbitone and carbamazepine, 60 min before induction of seizures. Behavioral parameters were assessed using elevated plus maze test and passive avoidance paradigm. Rat brain oxidative stress parameters were assessed and the serum levels of the AEDs were estimated. The AEDs in their therapeutic doses produced complete protection against seizures. However, sub-therapeutic doses of these AEDs failed to completely protect against seizures. Co-administration of curcumin with sub-therapeutic dose of valproate significantly increased the latency to myoclonic jerks. The percentage protection against seizures with sub-therapeutic doses of valproate, phenytoin, phenobarbitone and carbamazepine was also enhanced by concomitant curcumin administration. Both PTZ and MES induced seizures caused significant impairment of cognitive functions. Co-administration of curcumin with these AEDs in their sub-therapeutic doses prevented the impairment of learning and memory due to seizures whereas no such improvement was observed in the groups administered the sub-therapeutic doses of the AEDs alone. Additionally, curcumin reversed the oxidative stress due to seizures. However, curcumin co-administration did not cause any significant alteration in the serum levels of the AEDs. The results thus suggest the potential of curcumin as an adjunct to these AEDs in epilepsy with the advantage of increasing the efficacy, reducing the dose and side effects of the AEDs.     

松龄血脉康联合眩晕宁治疗脑供血不足眩晕135例疗效观察

目的 观察松龄血脉康胶囊联合眩晕宁片治疗脑供血不足所致脑源性眩晕的临床疗效.方法 将396例脑供血不足引起的脑源性眩晕患者随机分成三组:松龄血脉康胶囊组、眩晕宁片组和联合用药组.松龄血脉康胶囊组单用松龄血脉康胶囊1.5g,口服,3次/d,15 d为1个疗程;眩晕宁片组单用眩晕宁片2片,口服,3次/d,15 d为1个疗程;联合用药组用松龄血脉康胶囊1.5g,口服,3次/d,同时服用眩晕宁片2粒,口服,3次/d,15 d为1个疗程.疗效观察期为3个月.结果 松龄血脉康胶囊组、眩晕宁片组和联合用药组治疗有效率分别为63.6％(82/129),48.5％(64/132),83.7％(113/135).松龄血脉康胶囊组较眩晕宁片组,差异有统计学意义;联合用药组对脑源性眩晕的治疗有效率均较单独服用松龄血脉康胶囊组及单独服用眩晕宁片组高,差异有统计学意义.结论 松龄血脉康胶囊和眩晕宁片联合用药对治疗脑供血不足引起的脑源性眩晕效果明显优于单独用药.     

松龄血脉康胶囊联合氟桂利嗪治疗慢性脑供血不足的临床疗效

目的 探讨松龄血脉康胶囊联合氟桂利嗪治疗慢性脑供血不足的临床疗效。方法 选取2016年9月-2018年9月新疆心脑血管病医院158例慢性脑供血不足患者作为研究对象,根据随机抽签原则将患者分为对照组和观察组,每组各79例。对照组患者口服盐酸氟桂利嗪胶囊,1粒/次,1次/d;观察组患者在对照组的基础上口服松龄血脉康胶囊,1.5 g/次,3次/d。两组患者均连续治疗2个月。观察两组患者的临床疗效,同时比较两组治疗前后的脑血流速度和血脂水平。结果 治疗后,观察组患者总有效率为93.67%,对照组患者总有效率为77.22%,两组比较存在统计学差异（P<0.05）。治疗后,两组患者的各动脉血流速度均明显升高（P<0.05）,且观察组各动脉血流速度显著高于对照组（P<0.05）。治疗后,两组患者高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、三酰甘油（TG）和胆固醇（TC）水平均明显改善（P<0.05）,且观察组血脂水平显著优于对照组（P<0.05）。结论 松龄血脉康胶囊联合氟桂利嗪可有效改善患者的脑血流速度及血脂水平,临床疗效显著,在慢性脑供血不足治疗中具有较高的应用价值。     

The effect of cannabidiol,alone and in combination with ethanol,on human performance

Fifteen volunteers received cannabidiol (CBD) (320 g/kg) or placebo (both orally, T₀), and 60 min later they consumed an ethanolic beverage (0.54 g/kg) or placebo. The effects were measured at T₁ (100 min after CBD ingestion), T₂ (160 min) and T₃ (220 min) using cognitive, perceptual and motor function tests. Factorial analysis indicated that test procedures could be adequately expressed by three rotated factors: A reaction speed factor (I), a standing steadiness factor (II) and a psychomotor coordination/cognitive factor (III). Ethanol produced a significant decrement in factor III. There was no demonstrable effect of CBD, either alone or in combination with ethanol. Neither CBD nor ethanol produced any significant effect on pulse rate. Prior administration of CBD did not significantly affect the blood ethanol levels. Whilst the subjects were able to identify correctly when they were given ethanol, they did not report any subjective effects of CBD.     

松龄血脉康胶囊联合非洛地平治疗高血压的疗效观察

目的探讨松龄血脉康胶囊联合非洛地平片治疗高血压的临床疗效。方法选取2015年10月—2016年10月在上海市杨浦区五角场街道社区卫生服务中心接受治疗的高血压患者86例为研究对象,根据治疗方案的不同分为对照组和治疗组,每组各43例。对照组口服非洛地平片,1片/次,2次/d。治疗组在对照组基础上口服松龄血脉康胶囊,3粒/次,3次/d。两组患者均治疗4周。观察两组的临床疗效,比较两组的生活质量评分和血压变化。结果治疗后,对照组和治疗组的总有效率分别为81.40%、97.67%,两组比较差异有统计学意义(P0.05)。治疗后,两组躯体症状评分均显著下降,而健康愉快感评分、工作表现评分和生活满意度评分均显著升高,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标的改善程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者收缩压(SBP)和舒张压(DBP)均明显降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标的降低程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。结论松龄血脉康胶囊联合非洛地平片治疗高血压具有较好的临床疗效,可明显提高患者生活质量,降低患者血压,具有一定的临床推广应用价值。     

黄芪注射液对缺氧缺糖/复氧复糖大鼠海马神经元caspase-3表达的作用

目的观察黄芪注射液对缺氧缺糖/复氧复糖大鼠海马神经元凋亡相关基因caspase-3表达的影响。方法取原代培养8 d的大鼠海马神经元,随机分为4组:正常对照组、缺氧缺糖/复氧复糖组、黄芪注射液溶剂对照组和黄芪注射液组。除正常对照组外均进行缺氧缺糖0.5 h,再复氧复糖。各组于复氧复糖后0、0.5、2、6、24、48、72 h和120 h采用免疫组织化学染色法和Western blot检测caspase-3蛋白的表达,采用原位杂交检测海马神经元caspase-3 mRNA的表达。结果免疫组化结果显示:与正常对照组相比,除0 h和0.5h之外,缺氧缺糖/复氧复糖组各时间点海马caspase-3阳性神经元数目占神经元总数的百分率均明显增多(P<0.05),于24 h达到高峰。黄芪注射液溶剂对照组以上指标的变化趋势与缺氧缺糖/复氧复糖组相一致。黄芪注射液组除0 h和0.5 h之外,各时间点以上指标均比缺氧缺糖/复氧复糖组减少(P<0.05)。Western blot检测结果显示:除0 h和0.5 h外,各时间点缺氧缺糖/复氧复糖组海马神经元caspase-3蛋白的平均灰度值均较正常对照组明显增加(P<0.05),24 h最高;与缺氧缺糖/复氧复糖组相比,黄芪注射液溶剂对照组各时间点caspase-3蛋白的平均灰度值无变化(P>0.05),而黄芪注射液组除0 h和0.5 h外,在各个时间点caspase-3蛋白的平均灰度值明显降低(P<0.05)。原位杂交检测结果显示:caspase-3 mRNA阳性神经元形态、数目占神经元总数的百分率的变化趋势与caspase-3蛋白的变化趋势完全一致。结论黄芪注射液可抑制缺氧缺糖/复氧复糖大鼠海马神经元凋亡相关基因caspase-3的表达,从而抑制缺氧缺糖/复氧复糖大鼠海马神经元的凋亡。     

松龄血脉康胶囊联合谷维素片治疗阴虚阳亢型女性更年期综合征疗效观察

目的:观察松龄血脉康胶囊联合谷维素片治疗阴虚阳亢型女性更年期综合征的临床疗效.方法:选择2014年9月至2016年6月收治的女性更年期综合征患者118例,随机分为对照组54例,给予口服谷维素片治疗,每天3次,每次20 mg;治疗组64例,给予谷维素片和松龄血脉康胶囊(每天3次,每次1.5 g/次)治疗.两组均治疗4周,并随访30 d.治疗4周后评估总有效率,观察临床症状、体征改善时间、血清雌激素分泌变化.结果:治疗组和对照组的临床疗效分别为93.75％(60/64)和90.74％(49/54),组间差异无统计学意义(P>0.05).治疗组的症状、体征改善时间均优于对照组(P<0.05).治疗后治疗组血清雌激素E2水平为(5.02±2.54)pmol/L,优于对照组的(4.86±2.21)pmol/L(P<0.05).结论:松龄血脉康胶囊对缓解阴虚阳亢型妇女更年期综合征临床症状体征疗效明显.     

The time-dependent protective effect of hyperbaric oxygen on neuronal cell apoptosis in carbon monoxide poisoning

Introduction:?The progressive clinical course with delayed neurological damage in carbon monoxide (CO) poisoning may be due to neuron apoptosis. The usefulness of hyperbaric oxygen (HBO) in different time periods after CO exposure in neuronal cell apoptosis reduction has not been evaluated thus far. The aim was to evaluate HBO efficacy in reducing neuronal apoptosis in different time periods after CO exposure.

Methods:?Wistar rats were exposed to 3000?ppm CO in air for 60?min and 100% oxygen at a pressure of three bar for 30?min 0–12?h after CO exposure. The apoptosis was evaluated by immunohistochemical analysis with antibodies against activated caspase-3 and the percentage of caspase-3 positive hippocampal ganglionic cells was reported.

Results:?It was shown that CO poisoning results in ganglionic cell apoptosis. The percentage of apoptotic cells in rats exposed to CO was the highest (32%), whereas the percentage of apoptotic cells in rats exposed to HBO 0 and 1?h after CO was similar with a lower percentage than rats exposed to CO. The percentage of apoptotic cells in rats exposed to HBO 3 and 5?h after CO was similar with a lower percentage than rats exposed to HBO 0 and 1?h after CO. The percentage of apoptotic cells in rats exposed to HBO 7–12?h after CO was similar with a higher percentage than rats exposed to HBO 5?h after CO.

Conclusion:?HBO has a time-dependent protective effect on CO-induced neuron apoptosis with the highest efficiency at 3 and 5?h after CO poisoning.     

卡马西平对大鼠海马神经元形态的影响

目的 观察治疗剂量卡马西平对SD大鼠海马神经元形态的影响.方法 将成年雌性SD大鼠24只随机分为对照组与实验组(1周组、1月组及3月组),每组6只,对照组灌服等量蒸馏水,实验组治疗剂量卡马西平(20 mg/kg×6.25)每24 h单次灌胃给药后,于不同时间点经心脏灌注,取脑;尼氏组织化学染色法观察神经元的形态.结果 1周组海马区神经元的形态变化不明显(P>0.05),3月组神经元细胞水肿和空泡变性,差异有统计学意义(P<0.05).结论 治疗剂量的卡马西平对海马区神经元形态的影响具有时间依赖性,即随时间延长形态变化明显.     

桂芍镇痫片联合卡马西平治疗癫痫的临床研究

目的探讨桂芍镇痫片联合卡马西平片治疗癫痫的临床疗效。方法选取2017年5月—2018年5月江汉大学附属医院收治的78例癫痫患者为研究对象,所有患者根据治疗方法的不同分为对照组和治疗组,每组各39例。对照组口服卡马西平片,起始剂量0.2 g/次,2次/d,用药7 d后调整剂量,根据病情每周增加0.1～0.4 g,2次/d;治疗组在对照组治疗的基础上口服桂芍镇痫片,6片/次,3次/d。两组患者均连续治疗8周。观察两组的临床疗效,比较两组的癫痫放电、导联数目、癫痫发作次数、血清学指标和认知障碍评分。结果治疗后,对照组和治疗组的总有效率分别为74.36%、92.31%,两组比较差异有统计学意义(P0.05)。治疗后,两组癫痫放电、导联数目、癫痫发作次数均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清白细胞介素-2(IL-2)、肿瘤坏死因子-α(TNF-α)、神经元特异性烯醇化酶(NSE)和S100β蛋白(S100β)水平均明显降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组血清学指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组蒙特利尔认知评估量表法(MoCA)评分均显著升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组MoCA评分明显高于对照组,两组比较差异具有统计学意义(P0.05)。结论桂芍镇痫片联合卡马西平片治疗癫痫的临床疗效较好,能改善癫痫症状,提高认知水平,调节血清学指标,具有一定的临床推广应用价值。     

丙戊酸联合卡马西平治疗小儿癫痫的效果及对认知功能的影响

目的：探讨丙戊酸联合卡马西平治疗小儿癫痫的效果及对认知功能的影响。方法入选2012年6月~2013年2月就诊于本院的小儿癫痫患者98例作为研究对象,对其临床资料进行回顾性分析,按照应用药物不同分为单用A组34例、单用B组22例和联用C组42例,单用A组采用丙戊酸,单用B组采用卡马西平,联用C组采用丙戊酸联合卡马西平,对三组患者的疗效进行评价和分析,同时对药物治疗对认知功能的影响进行探讨。结果单用A组总有效率为67.65%,单用B组总有效率为63.64%,联用C组总有效率为85.71%,三组总有效率比较差异有统计学意义（P＜0.05）。单用A组认知障碍率为29.41%,单用B组认知障碍率为27.27%,联用C组认知障碍率为42.86%,差异有统计学意义（P＜0.05）。结论丙戊酸联合卡马西平较单用两种药物的疗效显著,但联用两种药物对认知功能的损害较严重,临床应注意合理应用,避免因追求疗效而忽视其对认知功能的严重损害。     

Effects of naltrexone alone and in combination with acamprosate on the alcohol deprivation effect in rats.

Previous research in our laboratory has shown that responding for ethanol increases after a period of imposed deprivation during which no ethanol is available (the alcohol deprivation effect). This selective increase in responding for ethanol was blocked by chronic administration of acamprosate. In the present study the effects of naltrexone and the combination of naltrexone+acamprosate on oral ethanol self-administration were examined following an imposed period of abstinence. Male Wistar rats were trained to respond for ethanol (10% w/v) or water in a two-lever free-choice condition. After training, separate groups of rats received chronic injections (2 x /day) of saline, naltrexone, or naltrexone+acamprosate during a 5-day period of abstinence. Ethanol self-administration was tested in all groups of rats on the last day of abstinence, 30 min after the last drug injection. Responding for ethanol increased significantly following the deprivation period in animals treated with saline. Chronic administration of naltrexone and the combination naltrexone+acamprosate blocked the increased ethanol consumption following the imposed abstinence period on post-deprivation Day 1. On post-deprivation Day 2, the combination of acamprosate with naltrexone blocked the rebound increase in ethanol consumption observed in animals treated with a low dose of naltrexone. These results support the hypothesis that naltrexone and acamprosate are effective in modulating aspects of alcohol-seeking behavior, and under certain situations may be more effective in combination.     

Effects of single doses of alprazolam and alcohol alone and in combination on psychological performance

The effects of alprazolam l mg alone and in combination with 0·5 g/kg of alcohol for males and 0·42 g/kg for females were examined on a range of psychological tasks 90 and 180 min post-drug (45 and 135 min post-alcohol). Forty-eight healthy volunteers were assigned randomly to four independent groups who received: alprazolam and placebo drink, alprazolam and alcohol, placebo capsule and alcohol, placebo capsule and placebo drink, respectively. Alprazolam caused subjective sedation, unsteadiness, dizziness and physical tiredness and impaired performance on all tasks. Alcohol caused similar subjective effects but little objective impairment. The effects of the combination were generally no greater than predicted from the sum of the single effects.     

对比分析卡马西平联合丙戊酸钠、单用卡马西平治疗癫痫的临床疗效及其不良反应

目的:分析卡马西平联合丙戊酸钠、单用卡马西平治疗癫痫的疗效及不良反应。方法:选择我院2018年1—12月收治的癫痫患者62例作为研究对象,按照治疗方法的不同分为研究组(卡马西平联合丙戊酸钠治疗)和对照组(卡马西平治疗),比较两组治疗前后的癫痫发作次数和每次发作时间、MoCA评分、HAMD评分、HAMA评分。结果:研究组临床指标在治疗后均显著优于对照组(P<0.05);两组不良反应发生率比较差异无统计学意义(P>0.05)。结论:卡马西平联合丙戊酸钠能有效改善癫痫发作次数和发作时间,提高认知水平,有利于情绪功能改善,疗效突出,安全性高,值得推广。     

人肾透明细胞癌中细胞凋亡相关因子Caspase-3和Caspase-9的表达

目的研究人肾透明细胞癌组织中细胞凋亡相关重要因子Caspase-3、Caspase-9表达的变化与肾癌的关系。方法标本离体后分成肾透明细胞癌组、癌旁组织组、正常肾组织组,均用10%的甲醛溶液固定48h,常规石蜡包埋、切片5μm,应用免疫组织化学方法进行观察研究。结果 Caspase-3与Caspase-9均在正常肾组织中可见少量弱阳性反应,癌旁组织阳性表达增加,肾癌组织表达明显减少,两两比较结果显示,3组之间差异均有统计学意义（P〈0.01）。肾癌4个期之间比较差异无统计学意义（P〉0.05）。Caspase-3与Caspase-9蛋白表达呈正相关（r=0.988,P〈0.05）。结论癌组织中Caspase-3和Caspase-9表达下降,说明细胞凋亡减少,癌组织细胞增殖旺盛,是肿瘤形成的重要机制。     

The effect of beta-adrenoceptor antagonists alone and in combination with a GABA-elevating agent on isoniazid-induced convulsions in rats

A delay in the onset of isoniazid-induced convulsions was found in rats pretreated with the beta 2-adrenoceptor blocker, butoxamine and the nonspecific beta-blocker, propranolol. In these animals the convulsive responses were inhibited in a dose dependent manner. These compounds were found to be effective even after the induction of convulsions. The beta 1-blocker, acebutolol was able to protect rats only when injected prior to the challenge. The anticonvulsant effect of acebutolol and propranolol but not that of butoxamine was found to be enhanced in animals pretreated with a gamma-aminobutyric acid (GABA) elevating agent, aminooxyacetic acid (AOAA). The findings indicate that the GABA-mediated anticonvulsant action of AOAA seems to be additive with that resulting from beta 1 but not beta 2-blockade.