桂枝汤方剂免疫抑制活性部位的考察

目的：筛选桂枝汤方剂免疫抑制活性部位。方法：处方药材分别水煎浓缩为水提部位,乙醇提取为乙醇提取部位。同时将乙醇部位分别用石油醚、氯仿、乙酸乙酯、 正丁醇萃取得石油醚部位、氯仿部位、乙酸乙酯部和正丁醇部位。CCK-8法考察桂枝汤不同提取物对ConA激活T细胞和LPS激活B细胞增殖的抑制作用。同时用二硝基氯苯对昆明种小鼠皮肤致敏和诱发,制成迟发型超敏反应模型,观察桂枝汤方剂不同部位对迟发型超敏反应的干预作用。结果：桂枝汤方剂水提物、乙醇提取物、石油醚萃取部位有显著免疫抑制功效,乙醇和石油醚提取物效果最佳。浓度200μg/ml时T细胞增殖抑制率分别为48.3%、45.9%,B细胞抑制率大于30%。乙醇提取物、石油醚萃取部位对迟发型超敏反应小鼠耳廓肿胀有显著抑制作用,对胸腺和脾脏无明显影响。结论：桂枝汤方剂乙醇提取物和石油醚萃取物为免疫抑制活性部位,能显著抑制T细胞和B细胞的增殖,抑制小鼠耳廓肿胀,对正常细胞、胸腺、脾脏无毒性。     

六月青萃取物对免疫抑制小鼠的影响

目的 研究六月青萃取物对环磷酰胺所致免疫功能抑制小鼠的影响。方法 小鼠腹腔注射环磷酰胺制作免疫抑制模型,测定血清肿瘤坏死因子α（TNF-α）和溶菌酶,计算胸腺指数、脾脏指数,观察六月青萃取物对免疫功能抑制小鼠的影响。 结果 六月青萃取物石油醚部位、氯仿部位、乙酸乙酯部位、水饱和正丁醇部位、60%乙醇部位能增加免疫抑制小鼠胸腺重量和提高血清溶菌酶含量;六月青萃取物乙酸乙酯部位、水饱和正丁醇部位、60%乙醇部位能提高免疫抑制小鼠血清TNF α含量,各极性部位对脾脏重量无显著影响。结论 六月青萃取物石油醚部位、氯仿部位、乙酸乙酯部位、水饱和正丁醇部位、60%乙醇部位能提高环磷酰胺所致免疫抑制小鼠的免疫功能。     

何首乌不同提取物对小鼠脾淋巴细胞的增殖作用

目的 研究何首乌不同提取物对小鼠脾脏淋巴细胞的增殖作用.方法 Con A诱导T细胞增殖;用XTT法测定淋巴细胞的增殖能力.结果 正丁醇和乙酸乙酯萃取物均能直接促进小鼠脾脏淋巴细胞增殖,并能增加Con A诱导的T淋巴细胞增殖,氯仿萃取物能抑制小鼠脾脏淋巴细胞增殖及Con A诱导的T淋巴细胞增殖.结论 何首乌的不同活性部位具有不同的免疫调节活性,提示何首乌可能具有双向的免疫调节作用.     

基于迟发型超敏反应及Th细胞因子分泌的玉屏风散不同分离部分筛选

摘要目的：以典型的迟发型超敏反应模型小鼠变应性接触性皮炎及脾淋巴细胞IFN-γ、IL-4的分泌,筛选玉屏风散抑制迟发型超敏反应的效应部分。方法：用二硝基氯苯来诱导小鼠变应性接触性皮炎,观察玉屏风散不同分离部分的干预作用;用MTF法检测玉屏风散不同分离部分对小鼠脾脏T淋巴细胞活化增殖的影响;采用ELISA法检测IFN-γ、IL-4的水平。结果：玉屏风散的醇提浓缩液能减轻小鼠耳廓的肿胀程度、显著抑制ConA诱导的T淋巴细胞增殖及IFN-γ、IL-4的分泌;乙酸乙酯萃取物能减轻小鼠耳廓的肿胀程度,显著抑制C0nA诱导的IFN-γ分泌,促进IL-4分泌;石油醚萃取物能抑制ConA诱导的IFN-γ、IL-4的分泌,整体模型未显示作用。三种提取物都不同程度地降低IFN-γ／IL-4比值,抑制Th1反应。结论：玉屏风散中抗迟发型超敏反应的效应成分主要在醇提液和乙酸乙酯部分,其作用与调节Th1／Th2的平衡有关;同时也提示以散剂为应用剂型是合理的。     

黄槿抗炎活性部位的初探

目的研究黄槿抗炎活性部位。方法采用70%乙醇提取药材,提取物用乙酸乙酯、正丁醇萃取,利用二甲苯致小鼠耳肿胀和醋酸致小鼠毛细血管通透性模型,观察黄槿提取物及其萃取物的抗炎活性。结果黄槿70%乙醇提取物及乙酸乙酯萃取物对二甲苯所致小鼠耳肿胀、醋酸致小鼠毛细血管通透性增加均具有显著抑制作用,与空白组比有显著差异(P<0.05),而正丁醇萃取物与生理盐水组对比没有显著差异(P>0.05)。结论黄槿提取物具有显著抗炎作用,并初步确定有效部位为乙酸乙酯萃取物。     

三种红毛七提取物的抗炎镇痛作用实验研究

目的初步探讨红毛七的乙醇、氯仿和正丁醇提取物的抗炎、镇痛作用,以了解红毛七产生镇痛抗炎作用的有效成分。方法取红毛七的乙醇、氯仿和正丁醇提取物,应用大鼠足跖肿胀法、小鼠耳廓肿胀法及小鼠去除双侧肾上腺素耳廓肿胀法、小鼠扭体法和热板法研究其抗炎镇痛作用。结果红毛七的乙醇和氯仿提取物对蛋清所致大鼠足趾肿胀有明显抑制作用;红毛七的乙醇、正丁醇提取物对二甲苯引起的耳廓肿胀有明显抑制作用;但对去除双侧肾上腺素的小鼠耳廓肿胀无明显作用;红毛七的乙醇、氯仿和正丁醇提取物能减少醋酸所致的小鼠扭体次数,延长小鼠热痛阈值。乙醇提取物的作用强于其他有机提取物。结论红毛七乙醇提取物有明显的抗炎、镇痛作用。     

香菇多糖对免疫抑制小鼠肠道派氏结T细胞的影响

目的研究香菇多糖对环磷酰胺免疫抑制小鼠的肠道派氏结T细胞的影响。方法通过胸腺指数,脾脏淋巴细胞的增殖转化和迟发型超敏反应情况观察香菇多糖对免疫抑制小鼠系统免疫功能的影响;在迟发型超敏反应条件下,通过肠道派氏结T细胞比例、亚群和活化的情况观察香菇多糖对免疫抑制小鼠肠道派氏结T细胞的影响。结果香菇多糖对环磷酰胺诱导的小鼠胸腺指数降低,脾淋巴细胞增殖和迟发型超敏反应能力下降表现出明显的恢复作用;对环磷酰胺诱导的DTH小鼠小肠派氏结数目减少,派氏结中T淋巴细胞比例升高、活化水平降低等肠道黏膜免疫系统抑制状态同样具有明显改善作用。结论香菇多糖可以正向调节免疫抑制小鼠肠道派氏结的T细胞功能,提示香菇多糖对肠道黏膜免疫系统具有一定的免疫调节作用。     

小钻提取物抗炎镇痛活性研究

目的筛选小钻抗炎镇痛活性部位,为小钻的开发利用提供实验依据。方法萃取法制备不同极性小钻提取物（石油醚提取物、乙酸乙酯提取物、正丁醇提取物、水提取物）。将小鼠分为正常组、阳性对照阿司匹林组（50 mg&#8226;kg－1）或洛芬待因组（含可待因6.76 mg&#8226;kg－1）和小钻石油醚、乙酸乙酯、正丁醇、水提取物组（500 mg&#8226;kg－1）,均灌胃给药7 d。通过二甲苯致小鼠耳肿胀、小鼠棉球肉芽肿的体内实验及各萃取物调节脂多糖（LPS）诱导小鼠巨噬细胞系RAW264.7细胞分泌一氧化氮（NO）水平的体外实验筛选抗炎活性部位,通过小鼠热板法、醋酸扭体法筛选镇痛活性部位。结果小钻乙酸乙酯提取物、正丁醇提取物、水提取物均能显著抑制二甲苯所致的小鼠急性耳廓肿和小鼠棉球肉芽肿（P＜0.05,P＜0.01）,且均能显著降低LPS诱导的RAW264.7细胞NO释放（P＜0.01）,具备一定抗炎活性;小钻乙酸乙酯提取物、正丁醇提取物、水提取物均能显著减少冰醋酸所致小鼠扭体次数,提高热板致痛鼠的痛阈（P＜0.05,P＜0.01）,具有一定的镇痛作用。结论小钻乙酸乙酯提取物、正丁醇提取物、水提取物均具有抗炎镇痛活性。     

猫爪草不同提取物对移植性肝癌H22小鼠的抗肿瘤作用

目的：探讨猫爪草不同提取物对移植性肝癌H22小鼠的抗肿瘤作用.方法：采用系统溶剂法提取分离猫爪草获得石油醚、氯仿、乙酸乙酯、正丁醇和水5个提取物.建立移植性肝癌H22小鼠模型后,检测各提取物灌胃给药10 d后的抑瘤率、生命延长率、肺脏指数、肝脏指数、脾脏指数和胸腺指数等.结果：石油醚提取物高、中、低剂量组对H22小鼠的肿瘤生长均无明显的抑制作用.氯仿、乙酸乙酯、正丁醇提取物高、中、低剂量组的抑瘤率（%）依次分别为51.78,48.80,33.33;55.51,45.10,31.36;32.71,25.08,24.64;生命延长率（%）分别为10.58,60.09,58.23;-1.05,56.91,45.09;60.98,59.76,50.84;水提物高、中、低剂量组的生命延长率（%）分别为74.98,74.76,50.05.水提物可以增加脾脏指数和胸腺指数.结论：猫爪草氯仿、乙酸乙酯和正丁醇提取物具有一定体内抗肿瘤作用,而水提取物具有一定的免疫调节作用.     

灰毛浆果楝提取物对菜青虫拒食活性的初步研究

对灰毛浆果楝根的95%乙醇提取物分别用石油醚、氯仿、乙酸乙酯、正丁醇等进行萃取获得各部分萃取物,分别对菜青虫进行拒食活性测试,结果显示灰毛浆果楝根的95%乙醇提取物的石油醚和氯仿萃取部分对菜青虫具有较好的拒食活性。     

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.