丹酚酸B对肾病综合征大鼠的改善作用

摘 要 目的：研究丹酚酸B对多柔比星致肾病综合征（NS）模型大鼠的改善作用。方法: 采用一次性尾静脉注射多柔比星制备NS模型,造模成功后给予大鼠丹酚酸B（0.2 g·kg-1、0.1 g·kg-1）连续灌胃5周,以醋酸泼尼松为阳性对照,探讨丹酚酸B对NS大鼠的肾脏指数、24 h尿量、24 h尿蛋白含量、腹水量及尿中钠、钾、氯离子的影响;以及对NS大鼠肾脏组织的影响。结果: 与模型组比较,丹酚酸B高剂量能显著提高NS模型大鼠的24h尿量和尿钠含量（P＜0.05）,降低24 h尿蛋白含量、腹水量和肾脏指数（P<0.05或P<0.01）,且上述指标与阳性药比较无差异（P>0.05）甚至更优（P<0.05）。对大鼠血钠、尿钾、尿氯等指标无影响（P>0.05）。丹酚酸B高剂量降低大鼠腹水含量的作用明显优于低剂量（P<0.01）,其他指标高低剂量组比较,差异无统计学意义（P>0.05）。丹酚酸B可改善NS模型大鼠肾小管蛋白管型。结论: 丹酚酸B具有提高NS大鼠尿量,尿钠排泄,降低尿蛋白,腹水含量及改善肾脏损害的作用。     

黄芪、灯盏花素复方制剂对阿尔茨海默病大鼠记忆能力及血、脑组织中超氧化物歧化酶、过氧化脂质和乳酸脱氢酶的影响

摘 要 目的：探讨黄芪、灯盏花素复方制剂（HDs）对阿尔茨海默病（AD）大鼠红细胞、脑组织中超氧化物歧化酶（SOD）、过氧化脂质丙二醛（MDA）以及乳酸脱氢酶（LDH）的影响。方法: 随机将50只大鼠分为正常对照组、脑复康阳性对照组（0.15 g·kg^-1·d^-1,灌胃）、模型组以及HDs低剂量（HDs1,1.5 ml·kg^-1·d^-1,腹腔注射）、HDs高剂量组（HDs 2,3.0 ml·kg^-1·d^-1,腹腔注射）,以三氯化铝（5 mg·kg^-1·d^-1,灌胃）和D 半乳糖（40 mg·kg^-1·d^-1,腹腔注射）建立AD大鼠动物模型。90 d后,测定各组大鼠的近期学习记忆能力,检测各组大鼠红细胞、脑组织SOD、MDA以及LDH水平。结果: 与AD模型组比较,HDs各剂量组大鼠学习记忆能力明显提高,红细胞及脑组织中SOD、LDH的活性明显升高,MDA含量明显降低,差异均有统计学意义(Ｐ<0.05或Ｐ<0.01);但尚未恢复至正常水平（Ｐ<0.05或Ｐ<0.01）。HDs2组部分指标明显优于脑复康阳性对照药组和HDs1组(Ｐ<0.05或Ｐ<0.01)。结论:黄芪、灯盏花素复方制剂对AD大鼠的学习记忆障碍有明显的改善,能有效提高AD大鼠红细胞及脑组织SOD、及LDH的活性,降低MDA的浓度。     

降脂片对非酒精性脂肪肝大鼠血脂和血清中ALT、AST、γ-GT水平的影响

摘 要 目的：观察降脂片对大鼠非酒精性脂肪肝 （NAFLD）的影响。方法: 72只雄性大鼠随机分为空白组、模型组、阳性药物组（东宝肝泰片,7.5 g·kg-1）、降脂片高、中、低剂量组（15,7.5,3.75 g·kg-1）。造模1周后开始给药,空白组和模型组给予同体积生理盐水,持续4周。末次给药2 h后,腹主动脉取血,检测血清中三酰甘油（TG）、总胆固醇（TC）、高密度脂蛋白（HDL C）、低密度脂蛋白（LDL C）,以及丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶(AST)、γ 谷氨酰基转移酶（γ GT）水平变化。结果: 与模型组相比,东宝肝泰片、降脂片高、中剂量组ALT、AST、γ GT、TG、TC、LDL C水平均显著降低,HDL C水平显著升高（P<0.05或P<0.01）;降脂片低剂量组ALT、AST、TC、TG水平显著降低（P<0.05或P<0.01）。结论: 降脂片对高脂饲料和灌胃高脂乳剂及腹腔注射低剂量CCl4建立的大鼠脂肪肝动物模型有较好的干预作用。     

情志刺激和内源性硫化氢与动脉粥样硬化发病的相关实验研究

摘 要 目的：观察情志刺激对动脉粥样硬化（AS）形成过程的影响,阐述硫化氢（H2S）在动脉粥样硬化病变中的作用。方法: 24只SD大鼠随机分为AS组、气滞血瘀型AS组和正常对照组,AS组给予特殊饲料,气滞血瘀型AS组给予特殊饲料+情志刺激,正常对照组给予普通饲料。造模期间,分别在第4、第8、第12周测定大鼠表征评分、H2S含量、凝血四项、组织血流量、血脂指标。结果: 气滞血瘀型AS组与AS组相比,第4周开始大鼠表征出现活动量明显减少、反应迟钝、被毛无光泽、舌质紫黯等现象(P<0.01);血脂明显升高,并随时间的增长而升高（P<0.05或P<0.01）;第8周开始活化部分凝血活酶时间（APTT）、纤维蛋白原（FIB）明显升高(P<0.05);第8周开始表皮、肝脏、肾脏组织血流量均明显减少;第12周时H2S的含量明显升高(P<0.01)。结论: 情志刺激促进了AS模型的形成,同时气体分子H2S体系在气滞血瘀型AS动物模型中也发挥了调节作用。     

乐食宝咀嚼片对幼龄厌食症大鼠模型的药理作用

摘 要 目的：研究乐食宝咀嚼片治疗厌食症的药理作用。方法: 大鼠随机分6组,每组10只,采用特制饲料喂养4周建立幼龄大鼠厌食症模型,从第8天起,每日给予乐食宝咀嚼片0.60,0.30,0.15 g·kg^-1,连续3周,期间观察大鼠一般状况并记录体质量和饮食量;测定胃液量、游离酸度、总酸度和胃蛋白酶活性;取血清采用测试盒方法测定总蛋白(TP)、白蛋白( Alb)、总胆固醇(TC)、胃动素（MTL）和胃泌素（GAS）的含量;以0.80,0.40,0.20 g·kg^-1剂量给予小鼠7 d,观察各组小鼠胃甲基橙排空率和小肠墨汁推进长度。结果: 乐食宝咀嚼片可明显增加幼龄厌食模型大鼠体质量和饮食量(P<0.05或P<0.01);促进胃液分泌和提高胃液中总酸及游离酸含量(P<0.05或P<0.01);能明显提高幼龄厌食模型大鼠胃蛋白酶活性(P<0.05或P<0.01);显著降低大鼠血清中TP、Alb及TC含量(P<0.05或P<0.01);升高血清中MTL和GAS水平(P<0.05或P<0.01)。同时能促进小鼠胃排空及小肠推进运动(P<0.05或P<0.01)。结论: 乐食宝咀嚼片可明显增加厌食症模型大鼠的摄食量和体质量,增强消化功能,对厌食症模型幼龄大鼠具有明显的治疗作用。     

骨炎方对家兔骨感染的预防

摘 要 目的：探讨骨炎方对家兔慢性骨髓炎的预防作用。方法: 家兔右胫骨骨髓腔内注射金黄色葡萄球菌建立慢性骨髓炎模型,分为正常对照组、模型组、庆大霉素组（60 mg·kg-1）、骨炎方高剂量组（3.6 g·kg-1）、骨炎方低剂量组（1.8 g·kg-1）,各组灌胃给药,术后第6周对右胫骨行X线检查并做Laurence评分;术前及术后第2,4,6周采血分别测定白细胞计数、血清溶菌酶（LZM）、血清C 反应蛋白（CRP）含量。结果: 骨炎方高、低剂量组对家兔骨髓炎症状有显著缓解,Laurence评分与模型组比较均有统计学意义（P<0.01）;与模型组比较,骨炎方高、低剂量组的白细胞计数在第2,4,6周均有明显降低（P<0.01）,而血清LZM含量则有明显升高（P<0.05或P<0.01）。与模型组比较,骨炎方高剂量组血清CRP含量在第2,4,6周均有明显降低（P<0.05或P<0.01）,低剂量组血清CRP含量在第4,6周均有明显降低（P<0.05）。与庆大霉素组比较,骨炎方高、低剂量组的白细胞计数在第4周有明显升高（P<0.05或P<0.01）;骨炎方高剂量组的血清LZM含量在第2、4、6周均有明显升高（P<0.01）,低剂量组的血清LZM含量在第2周有明显升高（P<0.05）;骨炎方高、低剂量组的血清CRP含量则在第6周有明显升高（P<0.01）。骨炎方高、低剂量组之间的Laurence评分、白细胞计数、血清LZM含量和CRP含量等差异无统计学意义。结论: 骨炎方对家兔骨感染的预防作用可能与抑制致病菌、提高机体免疫力、减轻炎症反应等途径有关。     

三七总皂苷肠溶微丸对高脂血症家兔血液流变学的影响

摘 要 目的：探讨三七总皂苷（PNS）肠溶微丸对家兔血液流变学的影响。方法: 建立空白对照组、模型组、血栓通注射剂（冻干）组（15 mg·kg^-1·d^-1,im）、PNS肠溶微丸高剂量组（45 mg·kg^-1·d^-1,ig）、中剂量组（30 mg·kg^-1·d^-1,ig）、低剂量组（15 mg·kg^-1·d^-1,ig）,予高脂饲料配方灌胃造模;运用血液流变学检测方法测定各组全血黏度、血浆黏度 、红细胞聚集指数、红细胞刚性指数、红细胞电泳率5项指标。结果: 模型组血液流变学5项指标明显高于空白对照组(P<0.01),提示动物模型复制成功。与模型组比较, PNS肠溶微丸高、中剂量组均能明显降低全血黏度和血浆黏度（P<0.01或P<0.05）;PNS肠溶微丸低剂量组能显著降低中切黏度及血浆黏度（P<0.05）;PNS肠溶微丸高、中、低剂量组红细胞聚集指数显著降低（P<0.01）;PNS肠溶微丸高、中剂量组红细胞刚性指数显著降低（P<0.01或P<0.05）;PNS肠溶微丸高、中、低剂量有降低红细胞电泳率的趋势,但差异无统计学意义（P>0.05）。PNS肠溶微丸中剂量组降低中切黏度效果优于血栓通注射剂（冻干）组（P<0.05）。结论:PNS肠溶微丸能降低家兔全血黏度、血浆黏度、红细胞聚集指数、红细胞刚性指数、红细胞电泳率等指标,发挥PNS肠溶微丸活血化瘀、抑制血栓形成、增加心脑血管的血液供应的作用。     

前列康和非那雄胺治疗良性前列腺增生的对比研究

摘 要 目的： 比较前列康和非那雄胺治疗大鼠良性前列腺增生的疗效。方法: 36只Wistar大鼠随机分成3组,去势14 d后皮下注射丙酸睾丸酮5 mg·kg^-1,前列康组按成人剂量10倍剂量灌胃给药,非那雄胺组按0.1 mg·kg^-1灌胃给药,对照组给予等量的蒸馏水,21 d后处死,称取前列腺湿质量,量取前列腺体积,光镜观察前列腺组织病理学改变。结果: 前列康和非那雄胺组大鼠前列腺湿质量分别为 （0.467±0.061）g,（0.408±0.058）g;大鼠前列腺体积分别为（0.371±0.059）ml,（0.365±0.054）ml,均显著低于对照组大鼠（P＜0.05）。结论: 前列康能显著抑制模型大鼠的良性前列腺增生,其机制可能是通过抑制前列腺细胞的增殖而实现的。     

益智膏滋对血管性痴呆大鼠脑损伤的作用研究

摘 要 目的：观察益智膏滋对血管性痴呆大鼠模型的影响。方法: 采用结扎双侧颈总动脉法制备血管性痴呆大鼠模型。益智膏滋高、中、低各剂量组大鼠连续灌胃给药30 d,采用Morris水迷宫的方法观察益智膏滋对大鼠学习记忆障碍的改善作用;采用生化方法检测各组大鼠血清中乙酰胆碱（Ach）、一氧化氮（NO）含量及一氧化氮合酶（NOS）活力;计算脑指数观察脑水肿状态;HE染色观测各组大鼠脑组织病理结构变化。结果: 与模型组相比,益智膏滋各给药组大鼠逃避潜伏期明显缩短(P<0.05),3min内找到平台次数明显增多(P<0.05),Ach含量明显升高(P<0.05),NO含量和NOS活力明显降低(P<0.05),脑指数明显降低(P<0.05),脑组织病理形态显著改善。结论: 益智膏滋能够明显提高血管性痴呆大鼠学习记忆能力,改善大鼠的脑水肿状态及脑组织病理形态,其作用机制与降低血清中NO含量和NOS活力,增强大鼠机体抗氧化损伤的能力,减轻脑组织损伤,进而提高Ach含量,增强胆碱能神经功能有关。     

五酯胶囊对万古霉素所致肾损伤大鼠的影响及其机制研究

摘 要 目的：探讨五酯胶囊对万古霉素诱导所致肾损伤大鼠的影响及其可能机制。方法: 24只雄性SD大鼠随机均分为空白对照组、模型对照组与五酯胶囊给药组,每组各8只。模型对照组与五酯胶囊给药组均连续每天1次尾静脉注射万古霉素200 mg·kg-1,空白对照组注射等剂量生理盐水,同时五酯胶囊给药组每天灌胃五酯胶囊混悬液0.25 g·kg-1,模型对照组与空白对照组则均灌胃等剂量蒸馏水。连续给药10 d后,检测大鼠血清中的胱抑素C（CysC）、肌酐（Scr）及尿素氮（BUN）水平、尿液中的24 h尿微量白蛋白（mAlb）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）及人肾损伤因子 1（KIM 1）水平及肾组织匀浆中的超氧化物歧化酶（SOD）、丙二醛（MDA）及谷胱甘肽过氧化物酶（GSH Px）水平,比较组间差异。结果: 模型对照组与五酯胶囊给药组的肾指数、CysC、Scr、BUN、mAlb、NGAL、KIM 1及MDA水平均较空白对照组显著升高（P<0.05或P<0.01）,且模型对照组升高幅度高于五酯胶囊给药组（P<0.05）;模型对照组与五酯胶囊给药组的SOD、GSH Px水平均显著低于空白对照组（P<0.05或P<0.01）,且模型对照组下降幅度大于五酯胶囊给药组（P<0.05）。结论: 五酯胶囊对万古霉素诱导所致肾损伤大鼠具有保护作用,可能与其抑制氧化应激作用有关。     

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.