苦参碱对脂多糖／痤疮丙酸杆菌诱导的小鼠肝炎及产生肿瘤坏死因子的影响

用小鼠致死性肝炎模型和ＴＮＦ体外诱生的方法，研究苦参碱（Ｍａｔ）对脂多糖（ｌｉｐｏｐｏｌｙｓａｃｃｈａｒｉｄｅｓ，ＬＰＳ）诱导的经痤疮丙酸杆菌（ｐｒｏｐｉｏｎｉｂａｃｔｅｒｉｔｔｍａｃｎｅｓ，ＰＡ）预刺激的小鼠产生肿瘤坏死因子（ＴＮＦ）以及致死性肝炎的影响。结果表明：Ｍａｔ（１０，５０ｍｇ·ｋｇ￣（－１），ｉｐ，ｂｉｄ×３ｄ）可降低血清ＴＮＦ和ＡＬＴ水平及小鼠对ＬＰＳ致死毒性的敏感性，并可在体外抑制ＬＰＳ诱导的经ＰＡ预刺激的小鼠腹腔巨噬细胞释放ＴＮＦ。提示Ｍａｔ的保肝作用与其抑制ＴＮＦ释放有关。     

苦参碱对脂多糖/痤疮丙酸杆菌诱导的小鼠肝炎及产生肿瘤坏死因子的影响

用小鼠致死性肝炎模型和TNF体外诱生的方法,研究苦参碱(Mat)对脂多糖(lipopolysaccharides,LPS)诱导的经痤疮丙酸杆菌(propionibacterittm acnes,PA)预刺激的小鼠产生肿瘤坏死因子(TNF)以及致死性肝炎的影响。结果表明:Mat(10,50mg·kg^-1,ip,bid×3d)可降低血清TNF和ALT水平及小鼠对LPS致死毒性的敏感性,并可在体外抑制LPS诱导的经PA预刺激的小鼠腹腔巨噬细胞释放TNF。提示Mat的保肝作用与其抑制TNF释放有关。     

复方痤疮胶囊对痤疮丙酸杆菌的抑菌和抗炎作用实验研究

目的:观察复方痤疮胶囊的药理学作用,为临床用药和进一步的开发研究提供理论依据.方法:用平板法37℃厌氧培养痤疮丙酸杆菌72 h,定量测定复方痤疮胶囊最低抑菌浓度,并观察其对二甲苯致炎剂所致小鼠耳廓肿胀的影响.结果:复方痤疮胶囊对痤疮丙酸杆菌的最低抑菌浓度分别为200 mg·ml-1;复方痤疮胶囊2.4 g·kg-1,1.2 g·kg-1能有效地降低二甲苯致炎剂所致小鼠耳廓的肿胀(P<0.01).结论:复方痤疮胶囊有明显的抑菌、抗炎作用.     

青心酮对小鼠动脉粥样硬化斑块中主要细胞TLR4表达的影响

目的:研究青心酮对小鼠动脉粥样硬化(AS)斑块中主要细胞(平滑肌细胞、内皮细胞、巨噬细胞)Toll样受体4(TLR4)表达的影响。方法:取小鼠胸主动脉,进行平滑肌细胞、内皮细胞的原代培养,RAW264.7细胞株传代培养。实验分5组,即对照、脂多糖(LPS)、辛伐他汀和青心酮高、低剂量组。应用RT-PCR及Western-blot方法检测TLR4mRNA表达及蛋白含量。结果:青心酮高剂量组血管平滑肌细胞、内皮细胞、巨噬细胞TLR4mRNA和蛋白含量显著低于LPS组(P<0.01)。结论:青心酮可下调LPS活化的小鼠平滑肌细胞、内皮细胞、巨噬细胞TLR4mRNA和蛋白的表达,其机制可能与通过TLR4途径发挥抗炎作用有关。     

化合物4h对脂多糖诱导RAW264.7细胞炎症的抑制作用及机制研究

摘要：目的:探讨化合物4h对脂多糖（LPS）诱导小鼠腹腔巨噬细胞炎症的抑制作用。方法:小鼠腹腔巨噬细胞RAW264.7经LPS诱导建立炎症模型,实验分为空白组、对照组、阳性罗格列酮组(5,10μmol·L-1)、阳性吲哚美辛组(5,10μmol·L-1)、4h组(5,10μmol·L-1),采用酶联免疫吸附实验测定目标化合物4h对于炎症因子肿瘤坏死因子α（TNF-α）分泌的影响;实验分为空白组、对照组、4h组(5,10μmol·L-1),采用蛋白免疫印迹实验测定目标化合物4h对于信号通路Toll样受体4/核因子κB（TLR4/NF-κB）蛋白的表达水平。结果:与空白组比较,LPS作用后,对照组TNF-α含量显著升高（P<0.01）,并且随着LPS作用时间的延长,TNF-α含量随之升高。加入化合物处理后,各实验组TNF-α含量呈下降趋势,与对照组比较,化合物4h各时间点的TNF-α含量差异均有统计学意义（P<0.05或P<0.01）,随着化合物浓度的升高,炎症因子的含量逐渐下降。化合物4h对TNF-α的抑制作用明显优于两个阳性对照药罗格列酮和吲哚美辛（P<0.05或P<0.01）。与空白组比较,LPS作用后对照组RAW 264.7细胞中IκBα蛋白表达水平显著降低,TLR4、p-NF-κB p65和p-IκBα蛋白表达水平显著升高（P<0.01）。与对照组比较,4h作用后实验组RAW 264.7细胞中IκBα蛋白表达水平显著升高,TLR4、p-NF-κB p65和p-IκBα蛋白表达水平显著降低（P<0.05或P<0.01）。结论:4h通过抑制信号通路TLR4/NF-κB蛋白的表达,进而抑制炎症因子TNF-α的产生,从而发挥抗炎作用。     

河北产蜂胶提取物对痤疮丙酸杆菌的抑制作用

目的探讨河北产蜂胶不同溶剂提取物对痤疮丙酸杆菌的抑制作用。方法采用微量板法培养痤疮丙酸杆菌,观察不同溶剂蜂胶提取物溶液对痤疮丙酸杆菌的抑菌效果,并确定其最低抑菌浓度(MIC)。结果蜂胶95%乙醇提取物对痤疮丙酸杆菌的MIC为512μg.mL-1;蜂胶75%乙醇提取物对痤疮丙酸杆菌的MIC为8μg.mL-1;蜂胶水提取物对痤疮丙酸杆菌的MIC为54μg.mL-1。结论河北产蜂胶不同溶剂提取物对痤疮丙酸杆菌均有较好的体外抑菌效果,蜂胶75%乙醇提取物的抑菌效果>蜂胶水提取物>蜂胶95%乙醇提取物。     

痤疮丙酸杆菌促树突状细胞前体细胞动员及其对胃癌的治疗效应

目的利用痤疮丙酸杆菌（P．aches）引起的炎症反应,促进小鼠外周血中树突状细胞（DC）的动员并研究P．aches动员的DC在体外对胃癌细胞的作用。方法C578BL／6J（B6）小鼠注射P．aches后外周血分离单个核细胞,用流式细胞仪分选F4／8013220-CD11c^＋细胞,在体外加入细胞因子GM-CSF、IL4和TNFα共培养,通过形态学观察、表型分析和混合淋巴细胞反应鉴定它们是否能分化为成熟DC。将P．aches动员的DC负载胃癌抗原后致敏T细胞,观察活化的T细胞在体外对胃癌细胞的杀伤效应。结果注射P．aches1h后外周血F4／80B220-CD11c^＋细胞数量即开始升高,24h后逐渐达到高峰。新鲜分离的细胞不具有成熟DC的特征。与细胞因子共培养后即具有典型的DC形态和表型,在混合淋巴细胞反应中具有极强的刺激T细胞增殖的能力。P．aches动员的DC负载胃癌抗原后致敏T细胞对胃癌细胞的杀伤率明显高于未致敏T细胞。结论P．aches可迅速动员F4／80-B220-CD11c^＋细胞进入小鼠外周血,经细胞因子的诱导后可分化为成熟DC,并可在体外诱导出针对胃癌细胞的特异性杀伤T淋巴细胞,对胃癌细胞有明显的杀伤作用,并伴有高水平的INF-γ分泌。     

黄芪注射液对脂多糖诱导的内皮细胞炎症因子产生的影响及其机制研究

目的:观察黄芪注射液对脂多糖(LPS)诱导的内皮细胞炎症因子产生的影响,并初步探讨黄芪注射液的抗炎作用机制。方法:体外培养的人脐静脉内皮细胞(HUVECs),待细胞生长到融合状态时加入不同浓度(10、20、40 mg/L)的黄芪注射液预处理2 h,然后加入LPS(1 mg/L)作用24 h。用四唑盐比色实验(MTT)检测细胞活力;半定量逆转录-聚合酶链式反应(RT-PCR)和酶联免疫吸附法(ELISA)分别检测内皮细胞细胞间黏附分子-1(ICAM-1)、白介素-8(IL-8)和肿瘤坏死因子-α(TNF-α)mRNA的表达和其在上清液中的含量;实时荧光定量PCR(real-time PCR)检测Toll样受体4(TLR4)mRNA的表达;凝胶电泳迁移率实验(EMSA)检测NF-κB活性。结果:LPS能明显降低细胞活力,并能显著增加ICAM-1I、L-8和TNF-αmRNA的表达和含量,同时TLR4 mRNA的表达和NF-κB的活性也显著升高,而预先应用不同浓度的黄芪注射液处理后,上述效应明显减弱。结论:黄芪注射液抑制炎症因子的产生可能与其抑制TLR-4/NF-κB信号通路有关。     

积雪草苷对哮喘幼鼠肺组织炎症和Toll样受体4/核因子-κB信号影响

目的 研究积雪草苷对哮喘幼鼠肺组织炎症和Toll样受体4(TLR4)/核因子-κB(NF-κB)信号影响.方法 幼鼠分成对照组、模型组(哮喘模型)、阳性对照组(地塞米松治疗)和低(10 mg·kg-1积雪草苷)、中(15 mg·kg-1积雪草苷)、高剂量实验组(20 mg·kg-1积雪草苷).以酶联免疫吸附(ELISA...     

黄酮类化合物与大环内酯类抗生素的协同抑菌作用机制

目的:观察芒果苷对痤疮主要致病菌的抑菌作用,探讨黄酮类化合物与大环内酯类抗生素的协同抑菌作用机制。方法:采用液体试管法培养金黄色葡萄球菌及痤疮丙酸杆菌,按试管称释法调整细菌浓度,观察芒果苷的抑菌作用。结果:单药使用时,芒果苷对痤疮丙酸杆菌及金黄色葡萄球菌的MIC分别为3 378.4,8 446.0mg.L-1,抑菌效果不明显;当与红霉素联合使用时,降低了红霉素的使用量,浓度为42.23mg.L-1的芒果苷与0.117mg.L-1的红霉素配伍使用,对上述两致病菌有抑制作用。结论:黄酮类化合物与大环内酯类抗生素具有协同抑菌作用,其作用机制极有可能是两者化学结构具有互补性,黄酮类化合物氧杂蒽酮C-葡萄糖苷的部分糖性基因在大环内酯类抗生素的大环内酯环上起到了修饰基团样的作用,由此,有望成为药物工业生产抗菌新药的根据。     

Benzoyl peroxide: a review of its current use in the treatment of acne vulgaris

Background: Owing to the use of topical and systemic antibiotics for acne vulgaris, the incidence of antibiotic-resistant Propionibacterium acnes is increasing worldwide. Topical benzoyl peroxide (BPO) is an alternative to antibiotics in the treatment of acne vulgaris. Objective: This review describes and evaluates recent clinical literature regarding the efficacy and tolerability of BPO. Methods: A PubMed literature search was conducted using the keywords benzoyl peroxide, acne, and combination therapy. Results: BPO is equally effective at concentrations of 2.5, 5.0 and 10%. However, a concentration-dependent irritant dermatitis can occur with higher concentrations. The efficacy of BPO can be enhanced when used in combination with topical retinoids, antibiotics and tertiary amines. BPO-containing combinations do not induce bacterial resistance and are important first-line treatments for mild to moderate acne vulgaris.     

Combination of azelaic acid 5% and clindamycin 2% for the treatment of acne vulgaris

Context and objective: Acne vulgaris, an inflammatory skin disease with different clinical appearances, is a common problem in most adolescents. It seems that using combinations of topical agents can decrease resistance to the treatment and improve the efficacy. Therefore, we evaluated the effects of azelaic acid (AA) 5% and clindamycin (Clin) 2% combination (AA-Clin) on mild-to-moderate acne vulgaris.

Materials and methods: The efficacy and safety of 12-week treatment with AA-Clin in patients with mild-to-moderate facial acne vulgaris were evaluated by a multicenter, randomized, and double-blind study. A total of 88 male and 62 female patients were randomly assigned to one of these treatments: AA 5%, Clin 2%, and combination of them. Every 4 weeks, total inflammatory and noninflammatory lesions were counted, acne severity index (ASI) was calculated, and patient satisfaction was recorded.

Results: Treatment for 12 weeks with combination gel significantly reduced the total lesion number compared with baseline (p?<?0.01), as well as Clin 2% or AA 5% treatment groups (p?<?0.05 or p?<?0.01). The percentage of reduction in ASI in combination treated group (64.16?±?6.01) was significantly more than those in the Clin 2% (47.73?±?6.62, p?<?0.05) and 5% AA (32.46?±?5.27, p?<?0.01) groups after 12 weeks. Among the patients in the AA-Clin group, 75.86% of males were satisfied or very satisfied and 85.71% of females were satisfied or very satisfied. This trend was significant in comparison to the number of patients who were satisfied with AA 5% or Clin 2% treatment (p?<?0.01). Seven patients in AA-Clin group (incidence?=?22%) showed adverse effects that were not statistically significant compared to treatment with individual active ingredients.

Discussion and conclusion: The profound reduction in lesion count and ASI by combination therapy with AA-Clin gel in comparison to individual treatment with 5% AA or Clin 2% suggested the combination formula as an effective alternative in treatment of acne vulgaris.     

重症脓毒症患者外周血单核细胞TLR4和炎性因子的表达及临床意义

目的 观察重症脓毒症患者外周血单核细胞(PBMC)膜结合CD14(mCD14)、TLR4及炎性因子的表达及临床意义.方法 选取符合重症脓毒症患者35例和健康志愿者15例作为对照.在患者被诊断重症脓毒症的第1、3、5天测定其外周血单核细胞mCD14、TLR4的表达及血清肿瘤坏死因子(TNF-α)、白细胞介素-10(IL-...     

Isovitexin alleviates acute gouty arthritis in rats by inhibiting inflammation via the TLR4/MyD88/NF-κB pathway

ContextThe prevalence of gout has greatly increased, and it has become the most common inflammatory arthritis in men. Isovitexin possesses anti-inflammatory and antioxidant properties.ObjectiveWe explored the effects of isovitexin on rats with acute gouty arthritis (GA).Materials and methodsFifty-four Sprague-Dawley rats were assigned to five groups: sham, model, positive (colchicine, 0.3 mg/kg), isovitexin (100 mg/kg), TLR4 inhibitor (TAK-242, 3 mg/kg) and isovitexin + TAK-242. The gait of rats and the ankle joint swelling index were monitored. The levels of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6, and pathological changes in the synovial tissues were determined.ResultsIsovitexin significantly reduced the ankle joint swelling index at day 7 compared to that in the model group (4.39 ± 1.01 vs. 6.09 ± 1.31). Moreover, isovitexin alleviated the infiltration of inflammatory cells and ameliorated the proliferation of synovial cells. The levels of TNF-α (93.42 ± 5.02 pg/mL), IL-1β (25.46 ± 1.91 pg/mL) and IL-6 (194.71 ± 7.92 pg/mL) in the isovitexin group were significantly lower than in the model group (129.39 ± 5.43, 39.60 ± 2.71 and 223.77 ± 5.35 pg/mL). The expression of TLR4, MyD88 and p-NF-κB-p65 was remarkably decreased after isovitexin and colchicine treatment. The effect of isovitexin was similar to that colchicine. Furthermore, the combination of isovitexin and TAK-242 had better effect, and there was no significantly difference with colchicine treatment.Discussion and conclusionsIsovitexin ameliorates joint inflammation in acute GA via the TLR4/MyD88/NF-κB pathway. Isovitexin may be a potential substitute medicine for GA.     

胎膜早破患者胎盘组织中TLR2和TLR4的表达及与绒毛膜羊膜炎的关系

目的研究胎膜早破患者胎盘组织中Toll样受体2（TLR2）和Toll样受体4（TLR4）的表达及其与绒毛膜羊膜炎的关系,探讨胎膜早破患者胎盘中Toll样受体变化的意义。方法选择胎膜早破患者60例（研究组）,同期正常晚期妊娠妇女40例（对照组）,采用免疫组化和RT-PCR法检测胎膜早破患者和正常晚期妊娠妇女胎盘组织中TLR2和TLR4的定位及表达,同时行产后胎膜病理检查。结果 TLR2、TLR4与胎膜完整与否无关,组织绒毛膜羊膜炎组TLR2表达明显比无组织绒毛膜羊膜炎增强（P〈0.05）;组织绒毛膜羊膜炎组TLR4表达比无组织绒毛膜羊膜炎增强,但差异无统计学意义（P〉0.05）;组织绒毛膜羊膜炎组TLR2和TLR4的RNA含量明显比无组织绒毛膜羊膜炎增加（P〈0.05）。结论 TLR2、TLR4与胎膜完整与否无关,有组织绒毛膜羊膜炎的患者,与TLR2和TLR4上调表达有关。这些研究对于理解先天免疫的生物学意义极为重要。     

清开灵含药血清对小鼠巨噬细胞Toll样受体及其下游信号转导通路的影响

清开灵具有清热解毒、化痰开窍和镇静安神等作用。现代药理研究表明其主要有解热[1]、抗炎免疫、保肝等作用。聚肌胞(POLY I:C)是TLR3的特异性配体,能诱导NF-κB和MAPK的活化。TLR3介导的信号途径中存在着MyD88非依赖途径[2,3]。细菌脂多糖(Lipopolysaccharide,LPS)是G-菌细胞成分之一,是TLR4的特异性配体。本实验观察了清开灵含药血清对LPS和POLY I:C刺激的RAW264·7细胞分泌炎症因子及其TLR3、TLR4和下游信号转导通路的影响。1材料与方法1.1药品及试剂清开灵口服液,北京中医药大学药厂;LPS、POLY I:C,美国Sigma公…     

三氟柳的合成工艺研究

目的 三氟柳合成工艺的优选.方法 通过试验考察不同酰化试剂、催化剂、反应温度、反应时间对合成工艺的影响.结果 以乙酸酐为酰化试剂和多聚磷酸为催化剂在50℃下反应30 min制得了高产率且高纯度的三氟柳.结论 该工艺简单,易于控制,产率高,为89.5%.