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1.
The susceptibility of several wild-type bacteria to ciprofloxacin and accumulation of the drug in these bacteria were evaluated. Species studied included Escherichia coli, Serratia marcescens, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis and Bacillus cereus. Ciprofloxacin susceptibility was measured for each strain using two different methods: the minimal inhibitory concentration and the bactericidal index. Significant differences were observed between the results derived from these two methods. Whereas the minimal inhibitory concentration was low in all strains tested, ciprofloxacin’s bactericidal activity, as indicated by the bactericidal index, varied with the species studied. To determine whether this finding was due to variations in cell envelope permeability to ciprofloxacin (i.e. to combined cell uptake and efflux), we studied ciprofloxacin accumulation using spectrofluorometry. In Gram-negative bacteria, differences in permeability can lead to altered susceptibility to antibiotics. In fact, the combination of slow uptake and efficient efflux seems to be crucial to the characteristic poor susceptibility of P. aeruginosa to ciprofloxacin. However, the low level of activity of ciprofloxacin against S. aureus and two Bacillus species may have resulted from the drug’s interaction with its target enzymes (i.e. topoisomerase IV in S. aureus and DNA gyrase in Bacillus spp.) rather than diminished permeability.  相似文献   

2.
The intestinal epithelium is exposed to oxygenated cholesterol products present in foodstuffs. In vitro studies demonstrate the effect of oxysterols on cytokine release by intestinal cells cultured alone. However, physiologically, the response of the intestinal epithelium to external agents occurs in the presence of dendritic cells (DCs). The aim of the study was to analyze the effect of 7-ketocholesterol on the barrier functions and IL-10 mRNA expression of Caco-2 cells in the presence of DCs, and secondly, on IL-10 mRNA expression in DCs. Caco-2 cells were co-cultured with monocyte-derived dendritic cells and induced with 7-ketocholesterol in a transwell system. DCs did not affect the transepithelial electrical resistance (TER) of the Caco-2 cell monolayer, but increased IL-10 mRNA expression in Caco-2 cells. 7-ketocholesterol decreased the TER of Caco-2 cells co-cultured with DCs and diminished IL-10 mRNA expression in Caco-2 cells induced by the presence of DCs. IL-10 mRNA expression fell in DCs co-cultured with Caco-2 cells after treatment with 7-ketocholesterol. Oxidized cholesterols present in gut mucosa may contribute to the decrease of epithelial barrier functions and the inappropriate development of an inflammatory response to food compounds.  相似文献   

3.
目的研究丹参茎叶总酚酸及其主要效应成分丹酚酸B和迷迭香酸组分单独或混合使用对溃疡性结肠炎(ulcera-tive colitis,UC)模型小鼠的保护作用,以期为丹参茎叶酚酸类成分的资源化利用提供科学依据。方法小鼠自由饮用2%葡聚糖硫酸钠7 d建立UC模型,再连续灌胃给药7 d,给药期间记录小鼠体重变化及疾病活动指数(DAI)评分。实验结束后,取结肠分别进行长度测量,HE染色,ELISA法测TNF-α、IL-6和IL-4含量,实时荧光PCR测IL-6、COX2和IL-17A mRNA水平。结果与正常对照组相比,模型组小鼠体重明显减轻,结肠明显短缩,结肠组织TNF-α、IL-6和IL-4水平及IL-6、COX2和IL-17A mRNA表达明显升高,丹参茎叶总酚酸及其主要效应成分丹酚酸B和迷迭香酸单独或混合给药干预后上述指标得到改善。结论丹参茎叶总酚酸及丹酚酸B和迷迭香酸单独或混合给药均能够改善UC模型小鼠肠道症状和减轻炎症反应,为丹参茎叶抗UC研究与开发利用提供了科学依据。  相似文献   

4.

Aim:

To explore the pathogenic role of Th17 cells and interleukin-17A (IL-17A)-associated signaling pathways in spontaneous pulmonary emphysema induced by a Toll-like receptor 4 mutant (TLR4mut).

Methods:

Lungs were obtained from wild-type (WT) or TLR4mut mice that were treated with or without recombinant mouse IL-17A (1 μg·kg−1·d−1, ip) from the age of 3 weeks to 3 months. Pulmonary emphysema was determined using histology, immunochemistry, and biochemical analysis. T cell polarization was determined with flow cytometry, the levels of cytokines were measured using ELISA, and the levels of IL-17A-associated signaling molecules were detected using Western blot.

Results:

Compared to WT mice, 3 month-old TLR4mut mice were characterized by significantly reduced infiltration of Th17 cells into lungs (2.49%±1.13 % νs 5.26%±1.39%), and significantly reduced expression levels of IL-17A (3.66±0.99 pg/μg νs 10.67±1.65 pg/μg), IL-23 (12.43±1.28 pg/μg νs 28.71±2.57 pg/μg) and IL-6 (51.82±5.45 pg/μg νs 92.73±10.91 pg/μg) in bronchoalveolar lavage fluid. In addition, p38 MAPK phosphorylation and AP-1 expression were decreased to 27%±9% and 51%±8%, respectively, of that in WT mice. Treatment of TLR4mut mice with IL-17A increased the infiltration of Th17 cells into lungs and expression levels of IL-17A, IL-6, and IL-23 in bronchoalveolar lavage fluid, attenuated MDA and apoptosis, and improved emphysema accompanied with increased phosphorylation of p38 MAPK and expression of AP-1.

Conclusion:

Th17 cells, in particular the cytokine IL-17A, play a crucial role in the pathogenesis of TLR4mut-induced spontaneous pulmonary emphysema. Both of them are potential targets for therapeutic strategies for pulmonary emphysema.  相似文献   

5.
目的探讨IL-17对人表皮细胞DNA荧光密度的影响。方法将正常人皮肤移植于裸鼠,建立人皮肤一裸鼠嵌合模型60只;按配对设计要求随机分成实验组30只和对照组30只,实验组注射IL-170.1ml(10ng/m1)于裸鼠移植皮肤内,对照组注射0.9%氯化钠0.1ml于裸鼠移植皮肤内,均1次,d,连续使用28d,最后以激光扫描共聚焦显微镜测移植皮肤人表皮细胞DNA荧光密度值。结果IL-17可使人表皮细胞DNA荧光密度值显著增加[实验组(2414.1667±309.4520)μ㎡VS.对照组(1865.8667±244.8843)μ㎡,t=7.6102,P〈0.05]。结论IL-17可促进人表皮细胞增殖过程中DNA含量升高。  相似文献   

6.
Composition of the gut microbiota changes with aging and plays an important role in age-associated disease such as metabolic syndrome, cancer, and neurodegeneration. The gut microbiota composition oscillates through the day, and the disruption of their diurnal rhythm results in gut dysbiosis leading to metabolic and immune dysfunctions. It is well documented that circadian rhythm changes with age in several biological functions such as sleep, body temperature, and hormone secretion. However, it is not defined whether the diurnal pattern of gut microbial composition is affected by aging. To evaluate aging effects on the diurnal pattern of the gut microbiome, we evaluated the taxa profiles of cecal contents obtained from young and aged mice of both sexes at daytime and nighttime points by 16S rRNA gene sequencing. At the phylum level, the ratio of Firmicutes to Bacteroidetes and the relative abundances of Verrucomicrobia and Cyanobacteria were increased in aged male mice at night compared with that of young male mice. Meanwhile, the relative abundances of Sutterellaceae, Alloprevotella, Lachnospiraceae UCG-001, and Parasutterella increased in aged female mice at night compared with that of young female mice. The Lachnospiraceae NK4A136 group relative abundance increased in aged mice of both sexes but at opposite time points. These results showed the changes in diurnal patterns of gut microbial composition with aging, which varied depending on the sex of the host. We suggest that disturbed diurnal patterns of the gut microbiome can be a factor for the underlying mechanism of age-associated gut dysbiosis.  相似文献   

7.
目的 分析甲泼尼龙冲击治疗对复发缓解型多发性硬化患者血清中IL-23及IL-17A水平的影响,为临床治疗复发缓解型多发性硬化提供参考.方法 选取我院2013年1月至2016年6月收治的52例复发缓解型多发性硬化患者作为观察组,并给予甲泼尼龙冲击治疗,选取同期于我院进行健康体检的52例志愿者作为对照组,比较两组阳性检出率、血清和脑脊液IL-23和IL-17A水平.结果 观察组治疗前血清中IL-23、IL-17A阳性检出率高于对照组,差异有统计学意义(P<0.05).治疗前观察组血清和脑脊液IL-23和IL-17A水平均高于对照组,差异有统计学意义(P<0.05);观察组治疗后血清和脑脊液IL-23和IL-17A水平均低于治疗前,差异有统计学意义(P<0.05).结论 复发缓解型多发性硬化患者血清和脑脊液IL-23及IL-17A呈高表达状态,这可能与其发病有关,甲泼尼龙冲击治疗可有效降低IL-23和IL-17A水平.  相似文献   

8.
目的比较不同剂量scBsAb1/17对Ⅱ型胶原(CII)诱导类风湿性关节炎(CIA)模型小鼠的治疗效果,及scBsAb1/17双特异性抗体与单价抗体(anti-IL-1βscFv和anti-IL-17scFv)在CIA模型小鼠中的治疗效果。方法利用CII建立小鼠类风湿性关节炎模型,小鼠成模后开始治疗,每2 d给药1次,治疗29 d。治疗结束后对小鼠关节炎指数进行临床评分,检测各组小鼠血清中CII抗体、CII特异性刺激的脾细胞增殖指数和脾脏中IL-2、IL-1β、IFN-γ、IL-6和TNF-α等细胞因子的表达水平。结果与CIA模型对照组相比,所有治疗组都能明显减轻CIA小鼠的临床症状,并明显降低血清中CII抗体水平、脾细胞增殖指数及脾脏中TNF-α、IL-6、IL-2、IL-1β和IFN-γ的表达量。相同剂量下scBsAb1/17治疗组的脾细胞增殖指数明显低于anti-IL-1βscFv治疗组(P<0.05);并且scBsAb1/17治疗组小鼠脾脏中IL-6、IL-2、IL-1β和IFN-γ的表达量明显低于anti-IL-1βscFv和anti-IL-17AscFv单独治疗组(P<0.01或P<0.05)。结论 scBsAb1/17及单价抗体对CIA模型小鼠都有治疗效果;不同剂量scBsAb1/17对CIA模型鼠的治疗效果呈剂量依赖性;相同剂量条件下,scBsAb1/17的治疗效果要优于单价抗体。  相似文献   

9.
目的探讨纤溶酶对在体小鼠肺泡液体清除率(AFC)的作用。方法应用考马斯亮蓝法测定小牛血清白蛋白浓度的方法测定小鼠在体AFC。结果特异性上皮细胞钠通道阻断剂阿米洛利组能明显降低AFC,气管内注入60μg/mL纤溶酶后,AFC明显增加(38.2±2.1)%,与对照组相比P<0.05,n=6)。纤溶酶+阿米洛利组对AFC的影响与对照组相比差异无统计学意义(P>0.05,n=5),与单独使用纤溶酶比较差异有统计学意义(P<0.05)。结论纤溶酶能明显增加肺泡上皮液体的清除,可能通过增强阿米洛利敏感性钠通道活性而影响AFC。  相似文献   

10.
Ochratoxin A (OTA) is a secondary metabolite produced by fungi of Aspergillus and Penicillium genra. OTA is mainly nephrotoxic but can also cause hepatotoxicity, mutagenicity, teratogenicity, neurotoxicity and immunotoxicity. As recent studies have highlighted the close relationship between gastrointestinal tract and kidney, as principal organs involved in absorption and respective excretion of xenobiotics, the aim of the present study was to analyze the effect of a subchronic exposure (30 days) to 0.05 mg/kg OTA on immune response and oxidative stress parameters at the level of intestine and kidney of young swine. The experiment was realised on twelve crossbred weaned piglets randomly allotted to both control group or toxin group fed 0.050 mg OTA/kg feed. Our results have shown that a subchronic intoxication with a low dose of OTA for 30 days affected the immune response and the anti-oxidant self-defense at gut and kidney level. The gene expression of both markers of signaling pathways involved in inflammation and inflammatory cytokines were affected in a much higher extent in the gut than in the kidney Of OTA intoxicated piglets.  相似文献   

11.
徐嘉琦  林以宁 《药学研究》2023,42(7):489-494
肥胖是全球性健康问题,与多种代谢疾病相关。肠道菌群的特定改变是肥胖和肥胖相关的代谢疾病的重要特征之一。近年来,肠道菌群在肥胖及相关代谢疾病中的作用受到了越来越多的关注,被认为是肥胖潜在的治疗靶点。肠道菌群的组成丰富,其参与宿主脂质代谢机制复杂。本文介绍了肥胖发生发展过程中的代表性菌种,概述了肠道微生物调控宿主脂质代谢的潜在机制的研究进展,以期为基于肠道菌群为靶点的治疗手段和药物研发提供思路。  相似文献   

12.
Sildenafil is the first oral therapeutic agent for the management of male erectile dysfunction. Its oral bioavailability is only 40% due to extensive presystemic elimination, mainly by CYP3A4. This study examined the effect of coadministration of ciprofloxacin or clarithromycin, which inhibit CYP3A4, on the bioavailability and pharmacokinetics of sildenafil. Twelve healthy male volunteers received sildenafil alone or after pretreatment with the inhibitors in a balanced three-way crossover design. The pharmacokinetic analysis showed that ciprofloxacin coadministration with sildenafil significantly increased the AUC from 1407 +/- 380 to 2986 +/- 917 microg h/l (90% confidence interval 119%-159%) and the Cmax from 287 +/- 67 to 623 +/- 192 microg/l (90% confidence interval 127%-152%). Similarly, clarithromycin coadministration increased sildenafil AUC from 1407 +/- 380 to 3209 +/- 762 microg h/l (90% confidence interval 127%-161%) and Cmax from 287 +/- 67 to 694 +/- 259 microg/l (90% confidence interval 132%-157%). Ciprofloxacin coadministration and clarithromycin coadministration with sildenafil did not affect the rate of sildenafil absorption significantly. These results indicate that coadministration of ciprofloxacin and clarithromycin significantly increased sildenafil bioavailability which can be attributed to the inhibitory effect of ciprofloxacin and clarithromycin on CYP3A4. Dose adjustment of sildenafil is thus necessary when administered with such drugs.  相似文献   

13.
Microbial components activate the host's innate immunity via interactions with molecules including TLRs and NODs. We previously reported that in mice (i) Escherichia coli lipopolysaccharide (LPS; TLR4 agonist) promotes Ni-allergy even in T-cell-deficient mice, (ii) E. coli LPS reduces the minimum allergy-inducing concentrations of Ni at both the sensitization and elicitation steps, and (iii) various microbe-related substances promote sensitization to Ni. Here, we examined the effects of microbe-related substances at the elicitation step. Mice (except for TLR4-mutated C3H/HeJ mice) were sensitized to Ni by intraperitoneal injection of NiCl2 + E. coli LPS. Ten days later their ear-pinnas were challenged with 1 μM NiCl2 with or without a test substance. Although NiCl2 alone at this concentration does not induce Ni-allergy, its combination with the following substances induced Ni-allergy in BALB/c mice: LPS preparations from oral Gram-negative bacteria (Prevotella intermedia and Porphyromonas gingivalis), a mannan preparation from a fungus (Saccharomyces cerevisiae), and synthetic NOD2 and TLR2 agonists. The effect of the mannan preparation was small in C3H/HeJ mice (sensitized with NiCl2 + the P. intermedia preparation). The P. intermedia preparation promoted Ni-allergy in C3H/HeJ and nude mice, but not in mice deficient in either TLR2 or histidine decarboxylase. Intragingival injection of the P. intermedia preparation and later challenge with NiCl2 alone to ear-pinnas also promoted Ni-allergy. These results indicate that (i) in Ni-allergy, a microbial milieu or innate immunity is important at the elicitation step, too, and (ii) some oral bacteria may promote Ni-allergy via TLR2-stimulant(s) production.  相似文献   

14.
目的:通过观察金乌健骨方含药血清对人类风湿关节炎滑膜细胞IL-17、IL-1α、IL-1β、TNF-α、IL-6分泌的影响,探讨其抗炎作用。方法:选取符合类风湿关节炎诊断标准的手术患者关节滑膜组织,进行原代滑膜细胞培养,并制备金乌健骨方兔含药血清,取3代对数生长期滑膜细胞加入不同浓度含药血清冻干粉,采用ELISA法检测IL-17、IL-1α、IL-1β、TNF-α、IL-6的分泌情况。结果:兔血清组IL-17、IL-1α、IL-1β、TNF-α、IL-6分泌量较空白对照组降低,但2组比较均无统计学差异(P>0.05)。各治疗组IL-17、IL-1α、IL-1β、TNF-α、IL-6的分泌量均较空白对照组降低(P<0.01,或P<0.05),金乌健骨方高剂量组(43 g·kg-1)对各炎性因子的降低最明显,对IL-17、IL-1β和TNF-α的降低作用优于雷公藤多苷组和强的松对照组(P<0.01,或P<0.05)。结论:苗药金乌健骨方能够抑制类风湿关节炎滑膜细胞的IL-17、IL-1α、IL-1β、TNF-α、IL-6的分泌。  相似文献   

15.
目的:观察三叶青藤正丁醇部位(nbuIR)对胶原性关节炎小鼠关节病变及血清炎症因子的抑制作用。方法:用DBA/1小鼠建立胶原性关节炎(CIA)动物模型,将造模成功小鼠随机分为模型对照组、甲氨蝶呤组、nbuIR低、中、高剂量组,另设正常对照组。灌胃给药,给药期间每周进行一次关节炎指数评分。干预结束后,ELISA法检测各组小鼠血清IL-23和IL-17水平,H-E染色观察各组小鼠踝关节组织病理学改变。结果:与模型对照组比较,nbuIR高剂量组血清IL-23和IL-17水平明显降低(P<0.01),滑膜细胞增生与炎症细胞浸润程度明显减轻。结论:nbuIR能改善CIA小鼠局部关节肿胀,下调血清IL-23和IL-17水平,减少滑膜炎症程度,其机制可能与调节IL-23/IL-17轴有关。  相似文献   

16.
In the present study, the influences of diets (i.e. chow and AIN-93 diets) on the interpretation of various fecal parameters including viable microbiota, moisture, weight, and short-chain fatty acids in rats fed different amounts of inulin (0.5–2 g/kg). Eight groups of rats (n = 8/group) were fed, for 4 weeks, chow or AIN-93 diets with or without inulin supplementation. Fecal samples were analyzed for different fecal parameters. After a 2-week adaptation, apparent differences in some fecal parameters were observed between the chow and AIN-93 diet groups. Throughout the 4-week intervention period, significantly (p < 0.05) higher Lactobacillus spp. counts, fecal moisture (∼2.7-fold), and fecal weight (∼5.8-fold) were observed with chow diet over AIN-93 diet. More specifically, significant elevations in the levels of Bifidobacterium spp., Lactobacillus spp., fecal moisture, and fecal weight could be observed at low-dose (0.5 g/kg) of inulin in chow diet groups, while most of these changes could merely be seen at medium-dose (1 g/kg) in AIN-93 diet groups. These results demonstrated that the choice of experimental diets would affect the comparison of fecal parameters as well as the interpretation of effective dosage of prebiotic in intestinal health assessments.  相似文献   

17.
海力特抗肿瘤作用及其对免疫功能的影响   总被引:2,自引:1,他引:2  
观察海力特(Hailite)的抗肿瘤作用及对机体免疫功能的影响。结果表明,海力特60,120mg·kg~(-1)对小鼠S_(180)实体瘤及小鼠肝癌H_(22)均有明显抑制作用(P<0.01);海力特10,20,40,80mg·kg~(-1)能明显促进小鼠腹腔巨噬细胞吞噬功能及提高血清溶血素含量,并能显著增强T淋巴细胞增殖活性及NK细胞杀伤靶细胞的活性,明显增加脾脏T细胞产生IL-2的能力。  相似文献   

18.
周丽俐  张婷  王佳 《现代药物与临床》2023,38(10):2405-2409
目的 研究六神丸对小鼠口腔溃疡的疗效及可能的作用机制。方法 将32只C57BL/6JGpt级小鼠随机分成对照组、模型组、六神丸组、桂林西瓜霜组,每组8只。于小鼠口腔左侧颊部黏膜上使用氢氧化钠片状晶体灼烧构建口腔溃疡模型。对口腔溃疡造模成功的小鼠分别外敷涂抹给予六神丸和桂林西瓜霜粉末0.375 g,连续5 d。观察小鼠口腔溃疡的恢复状态,用ELISA试剂盒检测血清白细胞介素(IL)-6、IL-8水平。取口腔溃疡部位组织,将溃疡组织制备匀浆,用二喹啉酸(BCA)法测定总蛋白浓度,并用Western blotting方法检测细胞外调节蛋白激酶(ERK)磷酸化水平。结果 与模型组比较,六神丸组小鼠口腔溃疡部位组织恢复情况较好,IL-6、IL-8水平显著降低(P<0.05),局部组织中ERK磷酸化水平降低。结论 六神丸对氢氧化钠灼烧的口腔溃疡小鼠模型具有一定治疗作用,且可能的机制是通过降低血液中IL-6和IL-8水平,进而导致局部组织中ERK磷酸化水平降低改善病理状态。  相似文献   

19.
Permeability edema is a life-threatening complication accompanying acute lung injury (ALI), severe pneumonia and the acute respiratory distress syndrome (ARDS), which can be associated with a reduced alveolar liquid clearance (ALC) capacity, a disruption of the alveolar epithelial barrier, and an increased capillary endothelial permeability. Bacterial and viral infections can directly promote pulmonary endothelial hyperpermeability and indirectly decrease the function and/or expression of ion transporters regulating ALC in type II alveolar epithelial cells, by means of inducing a strong inflammatory and oxidative stress response in the infected lungs. Apart from ventilation strategies, no standard treatment exists for permeability edema, making the search for novel regulators of endothelial and epithelial hyperpermeability and dysfunction important. Here, we present an overview of recently identified substances that inhibit and/or reverse endothelial barrier disruption and permeability or alveolar epithelial dysfunction: (1) zinc chelators, which were shown to attenuate the effects of oxidative stress on the pulmonary endothelium; (2) peroxisome proliferator activated receptor (PPAR) ligands, which have been shown to exert anti-inflammatory effects, by decreasing the expression of pro-inflammatory genes; (3) extracellular ATP, produced during inflammation, which induces a rapid and dose-dependent increase in transendothelial electrical resistance (TER) across pulmonary endothelial cells; (4) the lectin-like domain of TNF, which is spatially distinct from the receptor binding sites and which protects from hydrostatic and permeability edema and (5) Hsp90 inhibitors, which prevent and repair toxin-induced hyperpermeability. Unraveling the mechanism of action of these agents could contribute to the development of novel therapeutic strategies to combat permeability edema.  相似文献   

20.
目的 探讨蒲地蓝消炎口服液联合硫酸羟氯喹片治疗口腔扁平苔藓的效果。方法 选择唐山市人民医院在2020年11月—2023年6月收治82例口腔扁平苔藓患者,将所有患者根据随机数字表法分为对照组(41例)和治疗组(41例)。对照组口服硫酸羟氯喹片,1片/次,2次/d。治疗组在对照组基础上口服蒲地蓝消炎口服液,10 mL/次,3次/d。两组持续治疗4周。比较两组的临床疗效、体征积分、疼痛程度、口腔黏膜病损面积和血清指标。结果 治疗后,治疗组的总有效率(92.68%)明显高于对照组(75.61%),差异有统计学意义(P<0.05)。治疗后,两组的体征积分、数字疼痛强度量表(NRS)评分、病损面积均明显低于治疗前(P<0.05),治疗组的体征积分、NRS评分、病损面积均低于对照组(P<0.05)。治疗后,两组的血清白细胞介素-17(IL-17)、神经生长因子(NGF)、白细胞介素-12(IL-12)水平均低于治疗前(P<0.05),治疗组血清IL-17、NGF、IL-12水平均低于对照组(P<0.05)。结论 蒲地蓝消炎口服液联合硫酸羟氯喹片可提高口腔扁平苔藓的治疗效...  相似文献   

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