黄根片对四氯化碳致大鼠慢性肝损伤的影响

目的：探讨黄根片对大鼠慢性肝损伤的防治作用.方法：50只Wistar大鼠随机分为空白对照组、模型组、阳性对照组（联苯双酯滴丸,0.2 g·kg-1）、黄根片高、低剂量（36 g·kg-1,9 g·kg-1）组.除空白对照组外,其余各组大鼠每周2次皮下注射四氯化碳复制慢性肝损伤模型,同时每天灌胃给药1次,连续12周,观察黄根片对慢性肝损伤大鼠血液生化指标以及肝组织病理变化的影响.结果：与空白对照组比较,模型组大鼠造模后12周体质量、残留肝组织百分率显著降低,肝脏系数、肝组织Hyp含量、血清ALT、AST含量显著升高,血清TP、Alb含量显著降低（P＜0.05或0.01）.与模型组比较,黄根片高、低剂量组灌胃给药12周能够显著提高大鼠血清TP含量和残留肝组织百分率（P＜0.05）.结论：黄根片对四氯化碳致大鼠慢性肝损伤模型有一定的保护作用.     

重组牛胰蛋白酶抑制剂对四氯化碳致大鼠慢性肝损伤的保护作用

目的观察重组牛胰蛋白酶抑制剂(rBPTI)对大鼠慢性肝损伤的保护作用。方法大鼠98只,随机分成7组,分别为正常对照组、模型组、rBPTI3个剂量组(20,40和80MU.kg-1)、抑肽酶组(80MU.kg-1)和促肝细胞生长素组(100mg.kg-1)。除正常对照组外,其余各组皮下注射四氯化碳制备慢性肝损伤模型。8周后每天ip给药,给药4周后测定血清谷丙转氨酶(GPT)和谷草转氨酶(GOT)活性、白蛋白(Alb)含量、白蛋白/球蛋白(A/G)比值、唾液酸(SA)含量及肝组织羟脯氨酸(Hyp)含量,并进行组织病理学检测。结果与正常对照组比较,模型组大鼠血清GPT和GOT活性、SA含量及肝组织Hyp含量明显升高,血清Alb含量和A/G比值明显降低。与模型组比较,rBPTI各剂量组大鼠血清GPT和GOT活性、SA含量及肝组织Hyp含量降低,血清Alb含量和A/G比值明显增高。肝组织病理观察显示,rBPTI明显减轻由四氯化碳所致肝细胞脂肪变性及纤维组织增生等病理改变。结论rBPTI对四氯化碳诱导的大鼠慢性肝损伤具有保护作用和抗纤维化作用,在所观察的剂量范围内作用效果与抑肽酶相当。     

松花粉对酒精性肝损伤的保护功能研究

目的 研究松花粉对酒精性肝损伤的保护作用.方法 采用酒精复制大鼠肝损伤模型,测定肝组织的丙二醛(MDA)、甘油三脂(TG)及还原型谷光甘肽(GSH)含量;并观察肝脏的病理组织学改变.结果 受试样品大鼠肝组织的MDA、TG含量均低于肝损模型组;而GSH含量高于肝损模型组;各剂量组大鼠肝脏病理改变评分值均低于肝损模型组.结论 松花粉对酒精性肝损伤具有保护功能.     

黄芪胶囊对化学性肝损伤大鼠的治疗作用

目的通过黄芪胶囊对CCl4大鼠慢性肝损伤的治疗试验,评价黄芪胶囊保肝降酶的作用。方法大鼠sc 2 mL.kg-125%CCl4,每周2次,连续8周,制作大鼠慢性肝损伤模型。自给CCl4第5次后,开始ig黄芪胶囊,qd,连续5周,观察黄芪胶囊对CCl4造成大鼠慢性肝损伤的治疗作用。结果黄芪胶囊显著降低大鼠血清丙氨酸氨基转移酶、天门冬氨酸氨基转移酶,降低肝干重/湿重比值,降低肝系数,减轻肝组织病理损伤的程度,并增加肝细胞中肝糖原的含量。结论黄芪胶囊通过降低转氨酶,升高肝糖原水平,减轻肝脏损伤程度从而起到对CCl4引起大鼠肝损伤的保护作用。     

骨髓间充质干细胞移植对慢性胰腺炎大鼠模型胰腺纤维化的影响

摘要： 目的 观察骨髓间充质干细胞 （BMSCs） 移植对慢性胰腺炎大鼠模型胰腺纤维化的影响, 并探讨其作用机制。方法 将 30 只健康雄性 SD 大鼠随机分为对照组、 模型组和移植组, 每组 10 只。模型组采用胆胰管逆行注射油酸法制备大鼠慢性胰腺炎模型, 对照组以同样方式仅注射相同体积生理盐水, 移植组在造模后 1 周和 5 周经尾静脉注射 BMSCs。分别于造模后第 1、 4 和 8 周称量 3 组大鼠体质量, 于第 8 周后剖杀动物, 取胰腺组织行 HE 染色和饱和苦味酸-天狼猩红染色观察胰腺组织病理学改变并评分, 采用 ELISA 法检测胰腺组织转化生长因子 （TGF） -β1、 Ⅰ型胶原和Ⅲ型胶原含量。结果 造模后第 4 周, 模型组和移植组大鼠体质量均低于对照组 （P＜0.05）, 模型组与移植组间差异无统计学意义（P＞0.05）; 至第 8 周, 模型组和移植组大鼠体质量仍低于对照组, 而移植组高于模型组（P＜0.05）。模型组大鼠胰腺组织纤维化评分升高、 TGF-β1、 Ⅰ型胶原和Ⅲ型胶原含量均高于对照组和移植组（P < 0.05）; 移植组胰腺组织纤维化评分高于对照组, TGF-β1、 Ⅰ型胶原和Ⅲ型胶原含量与对照组差异无统计学意义。结论 BMSCs 移植能减少慢性胰腺炎大鼠胶原分泌, 降低胰腺纤维化程度, 其机制可能与抑制 TGF-β1分泌有关     

"神阙"透穴给药对慢性酒精性肝损伤大鼠的肝保护作用

目的:探讨"神阙"穴透穴给药对慢性酒精性肝损伤大鼠防护作用的机理.方法:成年SD大鼠40只随机分为空白组、模型组、治疗组和对照组.采用60°白酒灌胃9周,复制慢性酒精肝损害模型.治疗组"神阙"穴贴成品药贴,对照组"神阙"穴贴无药药贴.结果:治疗组能显著提高慢性酒精性肝损伤大鼠血清SOD活性,降低MDA含量,降低GGT活性,与模型组比较差异具有显著性意义.结论:"神阙"穴透穴给药能增强大鼠抗氧化能力,对慢性酒精性肝损伤有一定的防护作用.     

排毒护肝颗粒对实验性肝损伤的保肝作用的研究

目的：探讨排毒护肝颗粒对实验性肝损伤的保肝作用。方法将实验小鼠和大鼠分为正常对照组、模型组、排毒护肝颗粒高、中、低剂量组、联苯双酯组,共6组,分别观察排毒护肝颗粒对急性肝损伤小鼠的血清谷丙转氨酶（ALT）,谷草转氨酶（AST）的影响;对慢性肝损伤大鼠的血清ALT、AST、肝组织SOD、MDA、谷胱甘肽（GSH）、羟脯氨酸（Chyp）含量的影响,并对大鼠肝组织作HE病理切片观察。以评价排毒护肝颗粒的保肝作用效果。结果排毒护肝颗粒对D-氨基半乳糖造成的急性肝损伤小鼠和CCl4造成的慢性肝损伤大鼠和ALT,AST活性升高均有显著的降低作用。排毒护肝颗粒可显著升高CCl4慢性肝损伤大鼠肝组织SOD、GSH水平,降低MDA、Hyp水平。结论排毒护肝颗粒对D-氨基半乳糖造成的急性肝损伤和CCl4造成的慢性肝损伤均有显著的保肝作用。     

白花丹炮制前后对大鼠四氯化碳慢性肝损伤模型的影响

目的比较白花丹炮制前后对大鼠慢性肝损伤模型的影响。方法选用体重180~220 g SD大鼠,随机分为正常对照组,模型对照组,秋水仙碱组(1×10-4 g·kg-1),白花丹生品高、低剂量(10、5 g·kg-1)组,白花丹炮制品高、低剂量(10、5 g·kg-1)组。除正常对照组外,其余各组大鼠皮下注射40%四氯化碳花生油溶液,按0.6 m L/l00 g体重给予,每周2次,连续8周,造模2周后连续给药6周,实验结束后腹主动脉取血,检测血清中AST、ALT、ALB、TP及HA含量,另取适量肝组织检测Hyp、SOD、MDA含量。结果白花丹生品组出现毒性反应,有动物死亡,其余各组均无动物死亡现象。白花丹炮制品组实验后动物体重显著增长,而白花丹生品组这一现象不明显。白花丹生品组和炮制品组对大鼠慢性肝损伤模型血清AST、ALT、ALB、TP含量均有不同程度的降低作用,炮制品组降低AST、ALT作用与白花丹生品组相比显著增强。白花丹生品及炮制品对HA及Hyp含量均有不同程度的降低作用,均可提高肝损伤大鼠肝组织SOD活性,降低MDA含量,且呈剂量依赖性,炮制品效果更好。结论白花丹生品及炮制品对大鼠慢性肝损伤均具有一定的保护作用,白花丹炮制后能达到一定的减毒增效作用。     

维生素C和维生素E单用及联用对慢性酒精性肝损伤模型大鼠的预防性保护作用

目的:观察维生素C(VC)和维生素E(VE)单用及联用对慢性酒精性肝损伤模型大鼠的预防性保护作用。方法:取60只大鼠,随机均分为对照组、模型组、VC组(150mg·kg-1)、VE组(250mg·kg-1)和同剂量联合用药组(VC+VE组),除对照组给予等量生理盐水灌胃外,其余各组连续灌胃56°白酒建立慢性酒精性肝损伤模型,同时给予相应药物,每天1次,6周后检测各组大鼠血清丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST),肝匀浆中超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量,并观察肝组织病理学变化,免疫组织化学法检测肝组织中Ⅰ和Ⅲ型胶原的表达情况。结果:与模型组比较,VC组、VE组、VC+VE组ALT和AST活性、MDA含量、Ⅰ和Ⅲ型胶原表达均显著性降低(P<0.05),SOD活性显著性升高(P<0.05),肝脏炎症反应和纤维化明显减轻,且单用组和联用组之间无显著性差异。结论:VC和VE可能通过清除自由基和抑制脂质过氧化过程对慢性酒精性肝损伤模型大鼠发挥预防性保护作用。     

鲨鱼肝再生因子对大鼠慢性肝损伤的治疗作用

目的:探讨鲨鱼肝再生因子(sHRF)对大鼠慢性肝损伤的治疗作用。方法:CCl4致大鼠慢性肝损伤模型,给药后取血清及肝组织测定各项肝指标。结果:当用药8周时,对CCl4引起的肝损伤大鼠血清中AST、ALT活性的升高和羟脯氨酸含量的升高均有抑制作用,且0.8、1.6mg/kg剂量组的作用差异均有统计学意义。此外,sHRF能在一定程度上增加白蛋白含量,并使白蛋白/球蛋白比值有一定程度的升高。肝组织病理切片亦显示sHRF能减轻CCl4所致大鼠肝细胞脂肪变性及纤维组织增生。结论:sHRF对CCl4所致大鼠慢性肝损伤有一定的治疗作用。     

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.