冠心宁注射液对大鼠心肌缺血再灌注损伤的保护作用

目的:观察冠心宁注射液对大鼠心肌缺血再灌注损伤的保护作用,探讨冠心宁抗心肌缺血再灌注损伤的保护机理.方法:雄性SD大鼠30只随机分成假手术组(C组)、缺血再灌注组(I/R组)、冠心宁治疗组(G组),建立大鼠在体心肌缺血再灌注模型:C组丝线穿过冠状动脉前降支但不结扎,I/R、G组通过结扎心脏左冠状动脉前降支40 min,再灌注60 min制作缺血再灌注损伤动物模型.缺血前30 min,G组经腹腔注射冠心宁注射液10.0 ml·kg-1,余两组注射等量0.9%氯化钠注射液.测定再灌注60 min后心肌超氧化物岐化酶(SOD)活性及丙二醛(MDA)含量,同时取每组大鼠心肌检测梗死面积,电镜下观察缺血区心肌超微结构变化.结果:与I/R组相比,G组再灌注后60 min心肌MDA含量降低(P<0.01),SOD活性增高(P<0.01),梗死面积较小(P<0.01),心肌超微结构受损较轻.结论:冠心宁注射液对心肌缺血再灌注损伤有明显的保护作用,其机制与其增强心肌抗氧化作用有关.     

筋脉通对大鼠坐骨神经传导速度及红细胞抗氧化作用的影响

目的观察中药复方筋脉通对糖尿病大鼠坐骨神经传导速度及抗氧化作用的影响.方法采用链脲菌素(STZ)致大鼠糖尿病模型,给予筋脉通灌胃22.5g*kg-1,qd,并以氨基胍(AG)对照,疗程8周.观察该制剂对糖尿病大鼠坐骨神经传导速度和超氧化物歧化酶(SOD)活性、丙二醛(MDA)的影响.结果经筋脉通治疗后,糖尿病大鼠坐骨神经传导速度增快,和AG对照组、糖尿病组比较差异有显著性(P＜0.05～0.01).红细胞SOD活性与糖尿病组比较明显升高(P＜0.01),血浆MDA含量明显降低(P＜0.01).对血糖有降低作用.结论筋脉通能够提高STZ糖尿病大鼠SOD活性,降低MDA水平,增快神经传导速度,对改善糖尿病神经病变有一定的疗效.     

小牛血去蛋白提取物联合针灸治疗糖尿病神经源性膀胱50例临床观察

目的 观察小牛血去蛋白提取物注射液联合针灸治疗糖尿病神经源性膀胱的疗效.方法 将100例糖尿病神经源性膀胱随机分为观察组50例、对照组50例,两组基础治疗相同,观察组予静脉滴注小牛血去蛋白提取物注射液,并针刺肾俞、中极、关元、气海、水道、膀胱俞、三阴交等穴位;对照组仅静脉滴注小牛血去蛋白提取物注射液.治疗15 d观察疗效.结果 治疗后观察组膀胱残余尿量小于对照组,残余尿量减少值大于对照组,差异有统计学意义(P＜0.05).观察组总有效率(92%)明显高于对照组(66%),差异有统计学意义(χ2=8.42,P＜0.05).两组均无不良反应.结论 小牛血去蛋白提取物联合针灸治疗糖尿病神经源性膀胱安全有效.     

氯丙烯处理后大鼠大脑、脊髓和坐骨神经Gq/11α蛋白含量的变化

目的探讨氯丙烯引起周围神经病的机制.方法 Wistar雄性大鼠sc氯丙烯3个月后,用Western印迹方法分析测定大鼠大脑、脊髓、坐骨神经组织匀浆沉淀中Gq/11α蛋白含量的变化.结果在大脑沉淀中,75 mg*kg-1氯丙烯组使Gq/11α蛋白含量降低20%,150 mg*kg-1组降低25%(P<0.01);在脊髓沉淀中,75 mg*kg-1氯丙烯组使Gq/11α蛋白含量降低27%,150 mg*kg-1组降低63%(P<0.01);在坐骨神经沉淀中,未检测到Gq/11α蛋白.结论氯丙烯亚慢性中毒可导致大脑、脊髓神经细胞膜的Gq/11α蛋白相对含量减少,下调Gq-磷脂酶C信号传导通路.     

小牛血去蛋白注射液对大鼠脑缺血再灌注损伤的保护作用

目的：研究小牛血去蛋白注射液(depmteinised calf blood iniection，DCBI)对大鼠脑缺血及再灌注损伤的保护作用。方法：采用SD大鼠双侧颈总动脉结扎法制作不完全性脑缺血再灌注模型，观察DCBI对脑缺血再灌注SD大鼠的脑组织水含量，脑组织丙二醛(MDA)含量的影响，并通过光镜观察其病理组织学变化。结果：缺血组与缺血再灌注组脑组织水含量、MDA含量较假手术组明显增高；DCBI组脑组织水含量、MDA含量较缺血组与缺血再灌注组下降。病理组织学检查可见缺血组与假手术组相比大脑皮层细胞出现肿胀改变。缺血再灌注组脑组织水肿加剧，细胞周围呈海绵状。用药组脑细胞仅有轻度肿胀改变。结论：DCBI对大鼠脑缺血及缺血再灌注损伤具有保护作用。     

己酮可可碱通过抑制小胶质细胞激活减轻大鼠痛觉超敏和痛觉过敏

目的:观察己酮可可碱腹腔注射对大鼠坐骨神经分支选择性损伤致神经病理性疼痛的作用.方法:切断腓总神经和胫神经保留腓肠神经,制作坐骨神经分支选择性损伤模型.16只雄性SD大鼠从术前1 d起至术后6 d腹腔注射己酮可可碱100 mg·kg-1,qd.观察术前1 d和术后1,3,5,7和14 d大鼠的机械缩足反射阈值(MWT)和热缩足反射持续时间(TWD);并测定不同组别脊髓小胶质细胞标志物0X-42的表达.实验同时设假手术组和坐骨神经分支选择性损伤模型组(n=16).结果:大鼠坐骨神经选择性切断后1 d起MWT降低、TWD延长,与假手术组比差异有显著性统计学意义(P<0.05);己酮可可碱组MWT增加、TWD缩短,与模型组相比差异有显著性统计学意义(P<0.05);己酮可可碱组部分坐骨神经切断后脊髓0X-42的表达和小胶质细胞阳性细胞数均显著减少.结论:己酮可可碱腹腔注射可抑制坐骨神经分支选择性损伤致脊髓小胶质细胞的激活,减轻痛觉超敏和痛觉过敏.     

小牛血去蛋白提取物注射液对冠心病患者体表心电图的ST-T影响

目的观察小牛血去蛋白提取物注射液对冠心病患者体表心电图ST-T的影响。方法选择冠心病有缺血型ST-T改变的患者124例,每天静脉滴注小牛血去蛋白提取物注射液800mg,连用14d,观察用药前后心电图改变。结果治疗后缺血型ST-T明显改善,总有效率为80.95%。结论小牛血去蛋白提取物注射液能够明显减轻冠心病患者的心肌缺血,改善心功能,提高生活质量和运动耐量。     

脉络宁联合弥可保治疗糖尿病周围神经病变疗效观察

目的探讨脉络宁注射液联合甲钴胺（弥可保）治疗糖尿病周围神经病变的疗效。方法将115例入院患者随机分为2组,在常规治疗基础上,治疗组予脉络宁注射液联合甲钴胺肌肉注射治疗,对照组单用甲钴胺肌肉注射治疗,疗程均为1个月,观察治疗后症状改善情况,测定胫神经、腓总神经运动神经传导速度,肥肠神经、腓浅神经感觉神经传导速度。结果治疗组临床症状、神经功能评分、神经传导速度的改善情况均明显优于对照组（P均〈0.05）。结论脉络宁注射液联合甲钴胺治疗糖尿病周围神经病变安全有效,优于单独应用甲钴胺。     

前列地尔联合小牛血去蛋白提取物辅治糖尿病周围神经病变的疗效观察

目的 观察前列地尔联合小牛血去蛋白提取物辅治糖尿病周围神经病变(DPN)的临床效果.方法 将DPN患者100例随机分为治疗组和对照组,各50例.治疗组在常规治疗基础上给予前列地尔和小牛血去蛋白提取物治疗,对照组在常规治疗基础上给予甲钴胺.比较2组患者临床疗效及治疗前后的周围神经传导速度.结果 治疗组总有效率为90.0%高于对照组的76.0%,差异有统计学意义(P<0.05).2组治疗后正中神经和腓总神经的运动神经传导速度(MCV)及感觉神经传导速度(SCV)均快于治疗前,差异有统计学意义(P＜0.05);治疗后治疗组正中神经和腓总神经的MCV及SCV均快于对照组,差异均有统计学意义(P＜0.05).结论 前列地尔联合小牛血去蛋白提取物能有效治疗DPN,值得临床推广应用.     

降糖安脉胶囊治疗Ⅱ型糖尿病的实验研究

本实验用１％ＳＴＺ溶液注射于大鼠腹腔内，造成糖尿病动物模型，观察降糖发脉胶囊的治疗作用。结果表明：该方药可显著降低ＳＴＺ模型大鼠的空腹血糖；改善坐骨神经的传导功能；显著降低红细胞山梨醇含量；改善血液流变性和坐骨神经内微血管状态。提示降糖安脉胶囊可通过修复损伤的胰岛β细胞、促进胰岛素分泌、改善血液流变性和微循环、增加周围神经组织的血液供应和营养、抑制醛糖还原酶活性、阻断多元醇代谢通路等多种途径，实现     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.