鱼腥草总黄酮对小鼠结肠炎防治作用的研究

目的 探究鱼腥草总黄酮对小鼠结肠炎的防治作用。方法 采用纤维素酶协同超声波法提取鱼腥草总黄酮,以葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎为模型,通过分析小鼠体重、疾病指数、结肠系数、结肠病理切片、炎症因子等变化,阐明鱼腥草总黄酮对小鼠结肠炎防治的有效性。结果 鱼腥草总黄酮可有效改善DSS诱导性结肠炎造成的小鼠体重下降,并降低疾病指数、结肠系数和肝肾系数,有效抑制炎症因子的提高。结论 鱼腥草总黄酮可以改善结肠炎小鼠的结肠粘膜损伤,促进结肠粘膜结构修复,对小鼠结肠炎有显著的防治作用,可为今后的临床应用提供理论支持。     

槲皮素通过NLRP炎症小体相关通路对顺铂诱导肝损伤的保护作用

目的 探讨槲皮素通过NLRP炎症小体相关通路对顺铂诱导肝损伤的保护作用及其生物学机制。方法 在顺铂处理之前给小鼠灌胃槲皮素；通过血清生化分析和肝组织病理学分析检查小鼠的肝损伤情况；通过Western blotting检测凋亡相关蛋白和NLRP3炎症小体相关蛋白的变化。结果 槲皮素可通过抑制血清谷丙转氨酶和谷草转氨酶水平升高，恢复肝脏组织病理学改变，从而有效防治顺铂诱导的肝损伤。同时，槲皮素可以明显抑制氧化应激相关因子的产生，降低肝细胞凋亡，降低Bax、Bad、裂解的caspase-3和增加Bcl-2表达。此外，NLRP3炎性小体途径在槲皮素的作用下被灭活。结论 槲皮素可以抑制顺铂诱导的小鼠肝损伤，可能是通过调节NLRP3炎症小体相关途径来实现的。     

毛大丁草抗卵清蛋白诱导的小鼠支气管哮喘作用的活性部位筛选

目的 通过卵清蛋白(ovalbumin，OVA)诱导的支气管哮喘小鼠模型，筛选毛大丁草抗哮喘的活性部位。方法 采用D101大孔吸附树脂法对毛大丁草50%乙醇提取物进行分段富集，依次洗脱得到水、60%乙醇、95%乙醇3个洗脱部位。小鼠通过腹腔注射OVA致敏、雾化吸入OVA激发来复制哮喘动物模型，在激发阶段连续6 d进行灌胃给药治疗。采用行为学评分考察不同部位对哮喘行为学的影响，利用酶联免疫吸附法测定血清、肺泡灌洗液(bronchoalveolar lavage fluid，BALF)中IL-5的浓度和血清免疫球蛋白IgE的浓度，采用HE染色对肺组织进行组织病理学评价。结果 模型组小鼠哮喘症状评分升高，血清中IgE和IL-5的水平显著升高，BALF中IL-5的水平显著升高；与模型组比较，60%乙醇段高剂量组小鼠哮喘症状明显改善，血清中IL-5的水平显著降低，BALF中IL-5的水平也显著降低。结合病理学切片观察，60%乙醇段治疗的小鼠较之模型组小鼠肺泡间隔增厚程度降低，血管周围和支气管周围炎症细胞浸润显著减少。结论 毛大丁草50%乙醇提取物的60%乙醇洗脱部位为其抗哮喘的活性部位，其化学成分主要是酚酸类、黄酮类和香豆素类。     

银杏叶提取物注射液对脂多糖致大鼠急性肺损伤肺组织的保护作用

目的 观察银杏叶提取物注射液（GBE）对脂多糖（LPS）致大鼠急性肺损伤（ALI）肺组织的保护作用及其可能机制。方法 24只健康雄性Wistar大鼠随机分为对照组、LPS组和GBE组,每组8只。尾静脉注射LPS建立ALI模型,光镜下观察大鼠肺组织形态学改变;检测肺组织中超氧化物歧化酶活性（SOD）和丙二醛（MDA）含量及血清中白细胞介素-6（IL-6）的表达变化。结果 与对照组相比,LPS组肺组织中SOD活性降低、MDA含量增加、血清中IL-6含量增加（P<0.05）;应用GBE后,肺组织SOD活性升高、MDA含量减少、血清中IL-6含量减少（P<0.05）。结论 GBE可有效减轻ALI肺组织的炎症反应,其机制可能与其提高大鼠抗氧化能力、升高血清中IL-6的含量有关。     

固本平喘膏对慢性阻塞性肺病气道炎症的作用及机制

目的 通过建立大鼠COPD模型，观察固本平喘膏（GPO）对慢性阻塞性肺病（COPD）气道炎症的治疗作用并基于P2X₇受体（P2X₇R）探讨其作用机制。方法 采用香烟烟雾建立大鼠COPD模型，连续造模12周。造模第7周，将40只雄性SD大鼠随机分成5组，每组8只，即：模型组、GPO高、中、低给药组和阳性药地塞米松组，造模前另随机抽取8只大鼠作为正常组，正常组和模型组均灌胃给与等量生理盐水。观察GPO对COPD大鼠体重、肺功能、肺泡灌洗液（BALF）中炎症细胞、血清和BALF中炎症因子、病理、P2X₇R及其下游蛋白表达的影响。结果 GPO可以显著提高COPD大鼠的体重，改善COPD大鼠肺功能，并降低COPD大鼠BALF中炎症细胞、血清和BALF中炎症因子的水平；且病理结果表明，GPO可以改善COPD大鼠的病理变化；蛋白质免疫印迹（WB）结果表明，GPO显著逆转了COPD大鼠肺组织P2X₇R及其下游蛋白的异常表达。结论 GPO可以改善COPD气道炎症反应，其可能通过抑制P2X₇R信号通路发挥作用。     

木芙蓉叶抗氧化活性成分谱效关系研究

目的 比较木芙蓉叶不同极性部位的抗氧化活性，测定乙酸乙酯部位抗氧化活性并建立HPLC指纹图谱，研究谱效关系。方法 以DPPH法和ABTS法评价抗氧化活性，筛选木芙蓉叶抗氧化活性最佳部位，测定13批不同产地木芙蓉叶最佳部位的抗氧化活性，并建立HPLC指纹图谱，进行相似度分析、聚类热图分析以及主成分分析(principal component analysis，PCA)，并通过偏最小二乘回归法(partial least squares regression，PLSR)分析其谱效关系。结果 木芙蓉叶不同极性部位抗氧化活性强弱依次为乙酸乙酯部位>正丁醇部位>水部位>石油醚部位。13批木芙蓉叶乙酸乙酯部位有17个共有峰，共指认出5个成分，峰4为秦皮素，峰6为芦丁，峰8为异槲皮苷，峰10为山奈酚-3-O-芸香糖苷和峰15为银椴苷，13批样品的相似度在0.912~0.995。聚类热图分析和PCA将13批木芙蓉叶样品聚为两类；PLSR分析表明，峰3、峰4(秦皮素)、峰6(芦丁)、峰10(山奈酚-3-O-芸香糖苷)和峰12回归系数与抗氧化活性呈正相关，且贡献度较大(VIP>1)，为抗氧化活性的主要有效成分。结论 木芙蓉叶乙酸乙酯部位具有较好的抗氧化活性，木芙蓉叶抗氧化活性为多个成分协同作用的结果，揭示了木芙蓉叶抗氧化活性的药效物质基础。     

IL-22BP对肠炎相关性结直肠癌小鼠脾单核细胞和结肠组织炎症因子表达的影响

目的 探讨IL-22BP对肠炎相关性结直肠癌（colitis-associated colorectal cancer, CAC）小鼠脾单核细胞和结肠组织炎症因子表达的影响。方法 建立AOM/DSS诱导的CAC小鼠模型,观察给予IL-22BP后小鼠成瘤情况、结肠病理学改变、脾脏和结肠脏器指数,检测脾脏和结肠组织炎症因子IFN-γ、IL-17A、IL-22、IL-6和TNF-α的变化。结果 与模型组相比,IL-22BP组小鼠肿瘤数量明显减少,病理检测显示肿瘤评分和HAI评分均显著降低,脾脏指数和结肠指数显著下降,脾单核细胞和结肠组织 IFN-γ、IL-6和TNF-α水平增高,IL-17A水平降低,IL-22水平无明显改变。结论 IL-22BP可以调节CAC小鼠脾脏和结肠组织炎症因子IFN-γ、IL-17A、IL-6和TNF-α的水平。     

紫草素对慢性鼻窦炎小鼠鼻黏膜组织炎症反应及SIRT1/Nrf2信号通路的影响

目的 研究紫草素对慢性鼻窦炎小鼠鼻黏膜组织炎症反应及沉默信息调控因子1（SIRT1）/核因子E2相关因子2（Nrf2）信号通路的影响。方法 选取80只小鼠建立慢性鼻窦炎模型后随机分为模型组,紫草素12.5、50.0 mg/kg组,克拉霉素组,每组20只。另取正常饲养的20只小鼠设为假手术组。各组小鼠分别ig给予相应药物,1次/d,共14 d。采用苏木素-伊红（HE）染色观察小鼠鼻黏膜组织病理形态学;Masson染色观察小鼠鼻黏膜组织胶原沉积情况;ELISA法检测小鼠血清中炎性因子水平;Western blotting实验检测小鼠鼻黏膜组织中SIRT1/Nrf2信号通路相关蛋白表达。结果 与模型组比较,紫草素12.5、50.0 mg/kg组小鼠鼻窦黏膜慢性炎症表现和蓝色胶原沉积明显改善;血清中肿瘤坏死因子-α（TNF-α）、白细胞介素-32（IL-32）、γ干扰素（IFN-γ）水平显著降低;鼻黏膜组织中SIRT1、Nrf2、血红素氧合酶-1（HO-1）、NADPH醌氧化还原酶1（NQO-1）蛋白表达水平显著升高（P＜0.05）。且紫草素50.0 mg/kg组小鼠上述指标均显著优于紫草素12.5 mg/kg组（P＜0.05）。结论 紫草素能够改善慢性鼻窦炎小鼠鼻黏膜组织重塑和炎症反应,其作用机制可能与激活SIRT1/Nrf2信号通路有关。     

乳香及其炮制品对葡聚糖硫酸钠诱导小鼠炎症性肠病的保护作用

目的 研究乳香及其炮制品对葡聚糖硫酸钠（DSS）诱导的小鼠炎症性肠病的保护作用。方法 采用DSS水溶液代替正常饮水建立炎症性肠病小鼠模型,将实验小鼠分为对照组、模型组、柳氮磺胺吡啶（300 mg/kg）组、生乳香（0.76 g/kg）组、醋乳香（0.76 g/kg）组、生乳香粪清液（0.2 mL）组、醋乳香粪清液（0.2 mL）组,分别进行给药治疗。观察和监测小鼠体质量、粪便性状、便血情况,进行疾病活动指数（DAI）评分;记录结肠长度;运用苏木精–伊红染色法（HE）观察炎症性肠病小鼠肠道组织的病理变化;酶联免疫吸附试验（ELISA）检测炎症性肠病小鼠血清中白细胞介素（IL）-4、IL-10、IL-6、IL-1β的水平。采用蛋白质免疫印迹法（Western blotting）测定炎症性肠病小鼠肠道组织中肠黏膜机械屏障蛋白的表达情况。结果 生乳香、醋乳香、生乳香粪清液组和醋乳香粪清液组均可改善DSS造成的小鼠体质量下降、粪便性状评分和便血情况,显著降低DAI评分;改善炎症性肠病小鼠肠道组织的病理状态;调节血清中的炎症因子水平;显著升高炎症性肠病小鼠肠道组织中咬合蛋白（occludin）、紧密连接蛋白1（claudin-1）、闭合小环蛋白1（ZO-1）蛋白表达水平。结论 乳香及其炮制品可改善炎症性肠病小鼠炎症反应,对肠黏膜屏障具有一定的保护作用,且粪菌移植效果更佳。     

枣仁安神胶囊联合帕利哌酮治疗精神分裂症的临床研究

目的 观察丹蒌片对高脂喂养动脉粥样硬化模型ApoE^-/-小鼠的影响,从菌群失调诱发炎症角度探讨丹蒌片抗动脉粥样硬化的作用机制。方法 采用C57BL/6J野生型小鼠作为对照,高脂喂养ApoE^-/-小鼠24周后随机分为模型组、丹蒌片组,连续ig给药8周后取血测定血脂水平;ELISA法检测血清中脂多糖（LPS）水平;动脉大体油红O及主动脉窦HE染色观察斑块形成;粪便16 S rRNA扩增子测序检测肠道菌群;GC-MS法检测短链脂肪酸;实时荧光定量PCR法检测炎症因子肿瘤坏死因子-α（TNF-α）、细胞间黏附分子-1（ICAM-1）和白细胞介素-1β（IL-1β）mRNA的表达。结果 与对照组比较,模型组小鼠血脂水平升高,肠道菌群失调,有害菌增加,有益菌减少,血清LPS水平升高,主动脉周围炎症水平升高;与模型组比较,丹蒌片干预可明显降低小鼠总胆固醇（TC）、三酰甘油（TG）及低密度脂蛋白胆固醇（LDL-C）水平（P<0.01）,有效减少斑块面积;调节肠道菌群,进而降低血清LPS及主动脉周围炎症因子TNF-α、ICAM-1和IL-1β水平（P<0.01）。结论 丹蒌片通过改善菌群结构,降低菌群失调诱发的炎症反应发挥抗动脉粥样硬化作用。     

鼻渊净胶囊的HPLC指纹图谱研究

目的 建立鼻渊净胶囊的高效液相色谱（HPLC）指纹图谱。方法 采用Agilent SB-C₁₈（4.6 mm×250 mm,5 μm）色谱柱,乙腈-水为流动相、以1.0 ml/min流速行梯度洗脱,检测波长210 nm,柱温30 ℃,洗脱时间为80 min。采用中药色谱指纹图谱相似度评价系统（2004A版）对检测出色谱进行指纹图谱相似度评价。结果 建立了鼻渊净胶囊的HPLC指纹图谱,确定了20个共有峰,15个峰归属到各药材,其中5个峰确认了化学成分;10批样品的指纹图谱的整体相似度与对照图谱比较,均在90%以上。结论 所建立的鼻渊净胶囊指纹图谱有助于从整体上控制该制剂的质量。     

Synthesis and evaluation of 2,6-piperidinedione derivatives as potentially novel compounds with analgesic and other CNS activities

New 2,6-piperidinediones 2_a–g and 4_a–d were prepared by initial condensation of aromatic aldehydes or cycloalkanones with cyanoacetamide to give α-cyanocinnamides l_a–g or cycloalkylidenes 3_a,b which underwent Michae1 addition with ethyl cyanoacetate or diethylmalonate. Compounds 4_a–d were alkylated by various alkyl halides to produce the N-alkylated 2,6-piperidinedione derivatives 5_a–m. Some new selected compounds 2_a–c,f, 4_a–d & 5_e,h,j were pharmacologically evaluated for potential anticonvulsant, sedative and analgesic activities. These compounds exhibited significant anticonvulsant and analgesic effects after a single I.P. administration 100 mg/kg b.wt. . On the other hand all the investigated compounds induced hypnotic activity and prolonged the phenobarbital sodium- induced sleep as compared with the control group and the most potent compound was found to be 2_f.     

Investigation of the prevalence of tetQ, tetX and tetX1 genes in Bacteroides strains with elevated tigecycline minimum inhibitory concentrations

In this study, the antibiotic susceptibilities to tigecycline and tetracycline of 35 selected Bacteroides fragilis group strains were determined by Etest, and the presence of tetQ, tetX, tetX1 and ermF genes was investigated by polymerase chain reaction (PCR). tetQ was detected in all 12 B. fragilis group isolates (100%) exhibiting elevated tigecycline minimum inhibitory concentrations (MICs) (≥8 μg/mL) as well as the 8 strains (100%) with a tigecycline MIC of 4 μg/mL, whilst tetX and tetX1 were present in 15% and 75% of these strains, respectively. All of these strains were fully resistant to tetracycline (MIC ≥ 16 μg/mL). On the other hand, amongst the group of strains with tigecycline MICs < 4 μg/mL (15 isolates), tetQ, tetX and tetX1 were found less frequently (73.3%, 13.3% and 46.7%, respectively). All but two strains harbouring the tetQ gene in this group were non-susceptible to tetracycline, with a MIC > 4 μg/mL. These data suggest that in most cases tigecycline overcomes the tetracycline resistance mechanisms frequently observed in Bacteroides strains. However, the presence of tetX and tetX1 genes in some of the strains exhibiting elevated MICs for tigecycline draws attention to the possible development and spread of resistance to this antibiotic agent amongst Bacteroides strains. The common occurrence of ermF, tetX, tetX1 and tetQ genes together predicted the presence of the CTnDOT-like Bacteroides conjugative transposon in this collection of Bacteroides strains.     

喙果黑面神化学成分研究

目的研究大戟科植物喙果黑面神(Breynia rostrata Merr.)的化学成分。方法利用硅胶、凝胶等色谱技术分离纯化化学成分,根据化合物的理化性质和光谱数据进行结构鉴定。结果从喙果黑面神的正丁醇萃取部分分离得到4个化合物,分别鉴定为6-O-甲基丙酰基-α-D-吡喃葡糖(6-O-methylpropanoyl-α-D-glucopyranose,1);4″-苯酚基-6-O-甲基丙酰基-β-D-吡喃葡糖苷(4″-phenolic-6-O-methylpropanoyl-β-D-glucopyranoside,2);1-O-没食子酰基-β-D-吡喃葡糖苷(1-O-galloyl-β-D-glucopyranoside,3);熊果苷(arbutin,4)。结论化合物1和2为新化合物,3和4均为首次从该种植物分离得到。     

栝楼不同药用部位质量控制的研究进展

瓜蒌子、瓜蒌皮、瓜蒌、天花粉来源于栝楼的不同药用部位,4味药材均为常用的大宗药材,现行版《中国药典》对其制定的质量标准过于简单,无法科学合理地控制其质量。本文对瓜蒌子、瓜蒌皮、瓜蒌、天花粉安全性和有效组分的研究进行综述,明确了相关研究存在的问题并针对问题提出建议,为科学全面的药材及饮片标准的制定提供参考依据。     

Reassessment of the toxin profile of Cylindrospermopsis raciborskii T3 and function of putative sulfotransferases in synthesis of sulfated and sulfonated PSP toxins

The toxigenic freshwater cyanobacterium Cylindrospermopsis raciborskii T3 has been used as a model to study and elucidate the biosynthetic pathway of tetrahydropurine neurotoxins associated with paralytic shellfish poisoning (PSP). There are nevertheless several inconsistencies and contradictions in the toxin profile of this strain as published by different research groups, and claimed to include carbamoyl (STX, NEO, GTX2/3), decarbamoyl (dcSTX), and N-sulfocarbamoyl (C1/2, B1) derivatives. Our analysis of the complete genome of another PSP toxin-producing cyanobacterium, Raphidiopsis brookii D9, which is closely related to C. raciborskii T3, resolved many issues regarding the correlation between biosynthetic pathways, corresponding genes and the T3 toxin profile. The putative sxt gene cluster in R. brookii D9 has a high synteny with the T3 sxt cluster, with 100% nucleotide identity among the shared genes. We also compared the PSP toxin profile of the strains by liquid chromatography coupled to mass spectrometry (LC-MS/MS). In contrast to published reports, our reassessment of the PSP toxin profile of T3 confirmed production of only STX, NEO and dcNEO. We gained significant insights via correlation between specific sxt genes and their role in PSP toxin synthesis in both D9 and T3 strains. In particular, analysis of sulfotransferase functions for SxtN (N-sulfotransferase) and SxtSUL (O-sulfotransferase) enzymes allowed us to propose an extension of the PSP toxin biosynthetic pathway from STX to the production of the derivatives GTX2/3, C1/2 and B1. This is a significantly revised view of the genetic mechanisms underlying synthesis of sulfated and sulfonated STX analogues in toxigenic cyanobacteria.     

银杏叶提取物与刺梨配伍抗实验性肝损伤作用

目的：比较复方银杏叶胶囊（CGB）与单方银杏叶提取物（GBE）的保肝作用。方法：用CGB、GBE给小鼠灌胃30d后,腹腔注射CCl4诱发肝损伤,测定小鼠血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）及肝匀浆超氧化物歧化酶（SOD）、丙二醛（MDA）含量;用H2O2诱导人肝L-02细胞氧化损伤,观察细胞增殖及总抗氧化能力。结果：CGB2．4、0．8和0．4g／kg3个剂量组与模型组比较,小鼠血清ALT、AST明显降低（P〈0．01,P〈0．05）,同时肝匀浆中SOD显著升高、MDA下降（P〈0．01,P〈0．05）;CGB组细胞增殖率和总抗氧化能力分别较模型组和单方组显著提高（P〈0．05、P〈0．01）。结论：CGB的抗肝损伤作用优于单方银杏叶提取物。     

Chemopreventive effect of celecoxib in gastric cancer

COX (cyclooxygenase) is one of the key enzymes involved in the synthesis of a variety of prostaglandins (PGs), some of which have been strongly linked to inflammation. One of its two well-known isoforms, COX-2, is an inducible enzyme whose induction and expression is dynamically regulated by growth factors, mitogens, and tumor promoters. Several animal and clinical studies have reported the chemopreventive effect of celecoxib, a selective COX-2 inhibitor; and in particular, a few studies have shown that celecoxib prevents the development of gastric cancer. Administration of celecoxib also showed increases in cardiovascular risk and disruption of renal physiology. Therefore, studies hoping to clarify how selective COX-2 inhibitors modulate gastric cancer must keep in mind that coxibs have also been linked to serious cardiovascular events and disruption of renal physiology. Received 12 July 2006; accepted 21 August 2006     

Effect of bay K 8644, a calcium channel agonist,on dog cardiac muscarinic receptors

To investigate further whether the effects of the dihydropyridine (DHP) drugs on calcium channels are related to those of these drugs on muscarinic receptors, the binding characteristics of the DHP calcium channel agonist, Bay K 8644, on muscarinic receptors and calcium channels were compared to those of the DHP calcium channel antagonists, nicardipine and nimodipine in the dog cardiac sarcolemma. Bay K 8644, nicardipine and nimodipine inhibited the specific [³H]QNB binding with K _i values of 16.7μM, 3.5μM and 15.5μM respectively. Saturation data of [³H]QNB binding in the presence of these DHP drugs showed this inhibition to be competitive. Bay K 8644, like nicardipine and nimodipine, blocked the binding of [³H]nitrendipine to the high affinity DHP binding sites, but atropine did not, indicating that the muscarinic receptors and the DHP binding sites on calcium channels are distinct. The K _i value of Bay K 8644 for the DHP binding sites was 4 nM. Nicardipine and nimodipine (K _i :0.1–0.2 nM) were at least 20 times more potent than Bay K 8644 in inhibiting [³H]nitrendipine binding. Thus, the muscarinic receptors were about 4000 times less sensitive than these high affinity DHP binding sites to Bay K 8644. These results suggest that the DHP calcium agonist Bay K 8644 binds directly to the muscarinic receptors but its interaction with the muscarinic receptors is not related to its binding to the DHP binding sites on calcium channels.     

民族药材青阳参对照品的制备及质量标准提高研究

目的：建立青阳参苷甲对照品的制备方法和含量测定,为质量标准的提高提供参考。方法：采用植物化学方法制备青阳参苷甲作为对照品,采用质谱、核磁共振等光谱法鉴定对照品的结构,采用面积归一化法测定了对照品含量,并建立高效液相色谱法测定青阳参及同属药材白前、白薇和徐长卿中青阳参苷甲的含量。采用Waters X Select C18色谱柱（4.6 mm×250 mm,5 μm）,流动相为乙腈-水溶液（43：57）,流速1.0 mL·min^-1;检测波长223 nm;柱温30℃;进样量10 μL。结果：经过鉴定分离的青阳参苷甲纯度大于98%,可作为质量研究用对照品。青阳参苷甲质量浓度在5.62~224.8 μg·mL^-1（r=0.9998,n=6）范围内线性关系良好,方法的平均回收率（n=6）为97.7%（RSD=1.4%）。白前、白薇和徐长卿中未检出青阳参苷甲,青阳参中青阳参苷甲含量在0.015%~0.070%。结论：青阳参苷甲是青阳参的特征成分,可作为该药材的定量指标。本文所建立的高效液相色谱法可作为青阳参药材质量标准中的含量测定方法。