盐酸林可霉素与头孢拉定对BALB/c小鼠肠道菌群影响的比较研究

目的:比较盐酸林可霉素(LIH)与头孢拉定(CED)对BALB/c小鼠肠道菌群的影响。方法:将BALB/c小鼠随机分为LIH(330mg·kg-1)组和CED(165mg·kg-1)组,每组10只,分别灌服相应药物10d,停药7d,应用聚合酶链式反应-变性梯度凝胶电泳(PCR-DGGE)技术,对给药前和给药3、10d以及停药7d后2组小鼠粪便中的肠道菌群进行相似性、多样性分析及优势条带的序列分析。结果:2组给药前和停药7d后的肠道菌群结构相似,给药3、10d的肠道菌群结构相似,但2组给药前后菌群结构差异较大。实验期间2组肠道菌群均分为4个菌簇,其中LIH组给药前粪便标本中Clostridium carboxidivorans是定植菌,给药3d后卟啉单胞菌成为定植菌,Clostridium carboxidivorans消失;CED组给药前和给药3d的粪便标本中Clostridium carboxidivorans是定植菌,给药10d后卟啉单胞菌成为定植菌,Clostridium carboxidivorans消失;另2个菌簇在2组给药前后均变化不大。结论:2种药均可杀灭肠道中的定植菌Clostridium carboxidivorans,并在用药过程中产生致病菌卟啉单胞菌,导致肠道菌群失调。     

芒硝对正常小鼠肠道菌群的影响

目的：探究芒硝对小鼠肠道菌群的影响。方法：将SPF级ICR小鼠分为空白对照组、芒硝低剂量组和芒硝高剂量组。在灌胃3周后,无菌条件下收集小鼠粪便,扩增肠道菌群16SrRNA基因高变域V3-V4,检测小鼠肠道菌群的Alpha多样性、Beta多样性,线性判别筛选差异肠道菌群。结果：与对照组相比,高芒硝组小鼠肠道菌群丰富度提高;Beta多样性结果显示各组层级聚类均能较好地分开;线性判别分析显示在门、纲、目、科、属水平上,经芒硝处理后小鼠肠道菌群相对丰度会发生变化,其中高剂量芒硝组的Ruminococcus丰度明显提高。结论：芒硝能够调整肠道菌群内组成结构,提高菌群丰度,特别是益生菌的水平。     

丹参破壁饮片、常规饮片及传统粉末对小鼠肠道菌群的影响

目的研究丹参破壁饮片、丹参常规饮片及丹参传统粉末对小鼠肠道菌群的影响。方法 C57BL/6小鼠50只,随机分为5组,分别为空白组、常规饮片组、低剂量破壁饮片组、高剂量破壁饮片组及传统粉末组。连续灌胃给药14 d后,选择性分离培养粪便中双歧杆菌、乳酸杆菌、肠球菌及肠杆菌,鉴定和计数;并提取回盲部粪便的总DNA,进行PCR-DGGE(PCR-梯度凝胶电泳)分析,以观察小鼠肠道菌群的变化。结果细菌培养结果显示低剂量破壁饮片组及常规饮片组双歧杆菌及乳酸杆菌数量增加、肠球菌和肠杆菌数量则减少,差异有显著性意义;高剂量破壁饮片组及传统粉末中4种菌均无显著性差异。PCRDGGE结果显示,低剂量破壁饮片组的物种丰度和多样性指标均高于其他各组。结论丹参破壁饮片、常规饮片及传统粉末对肠道菌群无不良影响,且低剂量长期服用丹参破壁饮片对肠道菌群具有调整作用。     

饮水摄入抗生素对小鼠肠道菌群的影响

目的 采用抗生素饮水饲喂小鼠,观察抗生素对肠道菌群的影响。方法 高通量测序,分析肠道菌群的共有和特有OTUs、多样性和复杂度;PCA、NMDS、PCoA和UPGMA聚类树作多样本比较分析;聚类热图和柱状图分析小鼠肠道菌群相对丰度并预测肠道菌群功能的改变。结果 饮水摄入抗生素能够显著降低肠道菌群的物种丰富度、多样性、复杂度,升高优势菌群的总体占比,变形菌门的肠道细菌对抗生素的拮抗能力更强,并可能影响其功能。结论 抗生素具备改变肠道菌群的作用,需做好食品特别是饮用水受其污染的防控工作。     

中药903对实验性脾虚小鼠肠道菌群的影响

本实验用大黄水煎液造成小鼠实验性脾虚模型,引起小鼠肠道内菌群失调,再用中药9O3给小鼠灌胃,结果中药903Ⅰ号、Ⅱ号及促菌生均能使厌氧菌增加,对体内菌群失调具有调节作用。     

扶正固本丸对小鼠肠道菌群的影响

本文报告应用扶正固本丸对小鼠肠道内与人类关系密切的主要菌群的影响。用大黄水煎液灌胃予小鼠,造成实验性脾虚模型,引起小鼠肠道内菌群紊乱,其中双歧杆菌、乳杆菌菌量均下降,与对照组相比有显著性差异。当服用扶正固本丸后,双歧杆菌、乳杆菌均上升至正常值水平。本研究表明,扶正固本丸对小鼠肠道菌群的失调具有一定的促进作用。     

肠道菌定植饮对调节小鼠和斑马鱼肠道菌群功能的影响

目的：探讨肠道菌定植饮（DZY）对小鼠和斑马鱼的肠道菌群的调节作用。方法：设置DZY 3个剂量组0.41、0.82、2.46 g·kg-1·BW,连续灌胃30 d,测定灌胃前后小鼠粪便中肠杆菌、肠球菌、产气荚膜梭菌、乳杆菌、双歧杆菌菌落数;使用CM-DiI红色荧光标记青春双歧杆菌,DiO绿色荧光标记短乳杆菌;同时饲喂受精后5天（5 dpf）野生型AB品系斑马鱼,建立斑马鱼肠道菌群模型。将模型斑马鱼培养至6 dpf,移除短乳杆菌和青春双歧杆菌,分别给予DZY（1000、2000、4000 μg·mL-1）、阳性对照常欣卫口服液（8.30 μg·mL-1）,并设置模型对照组。24 h后,每个实验组随机取10尾斑马鱼置于荧光显微镜下拍照,分析肠道短乳杆菌、青春双歧杆菌的荧光强度。结果：DZY对小鼠肠道中的肠杆菌、肠球菌、乳杆菌数量无明显影响;但显著增加了双歧杆菌的数量,抑制了产气荚膜梭菌的生长。给予1000、2000、4000 μg·mL-1 DZY都能显著增加斑马鱼肠道中短乳杆菌、青春双歧杆菌的数量。结论：DZY能够在抑制条件致病菌的同时,增加有益菌的数量,具有调节肠道菌群的作用。     

中药903对抗生素脱污染小鼠肠道菌群的影响

本实验用抗生素给小鼠脱污染后,肠道菌群发生变化,尤其是乳杆菌和拟杆菌下降明显。中药903Ⅰ号、Ⅱ号对此有调节作用。均能使厌菌氧增加,需氧菌减少。     

两种泻药的安全性及对肠道菌群影响的对比研究

目的明确两种导泻药物对肠道菌群的影响以及是否会导致迟发性药物不良反应,探讨其相关性。方法将 2018年 10月至 2019年 6月深圳市龙岗中心医院收治的 61例拟行结肠镜检查的病人按随机数字表法、双盲分成两组, A组 31例、 B组 30例分别采用复方聚乙二醇电解质散、 20%甘露醇清洁肠道,于导泻前、导泻后 d1、d14取粪便送检,标本直接涂片法检测细菌总数、革兰阳性菌数量,稀释性平板菌落计数法 +快速细菌鉴定法检测肠球菌、大肠杆菌数量;导泻后 d14电话随访病人是否出现迟发性药物不良反应。结果导泻后 d1,两组细菌总数［ A组:(127.5±30.6)个/油镜比( 3 409.7±734.6)个 /油镜, B组:(110.9±     

Toxic effects of the food additives titanium dioxide and silica on the murine intestinal tract: Mechanisms related to intestinal barrier dysfunction involved by gut microbiota

This study aimed to compare the effects of three food-grade particles (micro-TiO₂, nano-TiO₂, and nano-SiO₂) on the murine intestinal tract and to investigate their potential mechanisms of action. A 28-day oral exposure murine model was established. Samples of blood, intestinal tissues and colon contents were collected for detection. The results showed that all three particles could cause inflammatory damage to the intestine, with nano-TiO₂ showing the strongest effects. Exposure also led to changes in gut microbiota, especially mucus-associated bacteria. Our results suggest that the toxic effects on the intestine were due to reduced intestinal mucus barrier function and an increase in metabolite lipopolysaccharides which activated the expression of inflammatory factors downstream. In mice exposed to nano-TiO₂, the intestinal PKC/TLR4/NF-κB signalling pathway was activated. These findings will raise awareness of toxicities associated with the use of food-grade TiO₂ and SiO₂.     

罗红霉素胶囊溶出度考察

目的:对不同厂家的罗红霉素胶囊进行溶出度比较。方法:采用2000年药典规定的方法测定溶出度,并对其溶出参数(Td、T50、m)进行统计处理。结果:不同厂家之间溶出速率相差很大(P<0.01),B厂最快,C厂最慢。结论:不同厂家的产品内在质量有显著差别。     

Immunosuppressive effects of rutaecarpine in female BALB/c mice

Rutaecarpine is a major quinazolinocarboline alkaloid isolated from Evodia rutaecarpa. It was reported to possess a wide spectrum of pharmacological activities, such as vasodilation, antithrombosis, and anti-inflammation. In the present study, adverse effects of rutaecarpine on immune functions were determined in female BALB/c mice. Rutaecarpine had no effects on hepatotoxicity parameters in mice, as measured by serum activities of aminotransferases. Meanwhile, rutaecarpine significantly decreased the number of antibody-forming cells and caused weight decrease in spleen in a dose-dependent manner, when mice were administered with rutaecarpine at 10mg/kg, 20mg/kg, 40 mg/kg or 80 cmg/kg once intravenously. In addition, rutaecarpine administered mice exhibited reduced splenic cellularity, decreased numbers of total T cells, CD4(+) cells, CD8(+) cells, and B cells in spleen. IL-2, interferon-gamma and IL-10 mRNA expressions were suppressed significantly by rutaecarpine treatment. The number of CD4(+)IL-2(+) cells was reduced significantly following administration of mice with rutaecarpine. Furthermore, rutaecarpine caused the cell cycle arrest in G(0)+G(1) phase in a dose-dependent manner. Rutaecarpine caused significant inductions of hepatic cytochrome P450 (CYP) 1A, 2B, and 2E1 activities dose-dependently. In the splenic lymphocyte proliferation assay, rutaecarpine inhibited proliferation by LPS and Con A ex vivo, whereas it had no effects on in vitro proliferation. These results suggested that a single bolus intravenous injection of rutaecarpine from 20mg/kg might cause immunosuppressive effects, and that rutaecarpine-induced immunosuppression might be mediated, at least in part, through the inhibition of cytokine production and cell cycle arrest in G(0)+G(1) phase, and caused possibly by mechanisms associated with metabolic activation.     

罗红霉素薄层层析方法的比较及应用

建立了罗红霉素新的ＴＬＣ法，并与《日本抗生物质医药品基准解说》１９９３年版收载的方法进行了比较。认为新法较之原法具有分离效果好、灵敏度高、背景浅等优点。将新的ＴＬＣ法用于罗红霉素的有关物质及分解产物检查，结果令人满意。     

In vitro potential cytogenetic and oxidative stress effects of roxithromycin

Macrolide antibiotic roxithromycin was evaluated in terms of its genotoxic, cytotoxic and oxidative stress effects. For this purpose; 25, 50, 100 and 200?μg/mL concentrations of roxithromycin were dissolved in dimethyl sulfoxide and treated to human peripheral blood lymphocytes for two different treatment periods (24 and 48?h). In chromosome aberration (CA) and micronucleus (MN) tests, roxithromycin did not show genotoxic effect. But it induced sister chromatid exchange (SCE) at the highest concentration (200?μg/mL) for the 24-h treatment period and at all concentrations (except 25?μg/mL) for the 48-h treatment period. Looking at cytotoxic effect of roxithromycin, statistically insignificant decreases on mitotic index and proliferation index were observed. Roxithromycin decreased nuclear division index (NDI) at highest two concentrations (100 and 200?μg/mL) for the 24-h treatment period and at all concentrations (expect 25?μg/mL) for the 48-h treatment period. Total oxidant values, total antioxidant values and oxidative stress index did not change with roxithromycin treatment. Eventually, roxithromycin did not have genotoxic and oxidative stress effects in human-cultured lymphocytes.     

The paradoxical effects of lead in interferon-gamma knockout BALB/c mice.

It has been reported that lead (Pb) exposure enhances interleukin (IL)-4 and inhibits interferon-gamma (IFNgamma) production in wild-type (WT) BALB/c mice. Here, we examined Pb effects on immunity in IFNgamma knockout (KO) mice. Lead significantly enhanced serum IgG1 anti-keyhole limpet hemocyanin (KLH) levels in WT mice compared to the controls; Pb also increased serum IgG2a anti-KLH levels, but the IgG1:IgG2a ratio was greater with Pb. In addition, total serum IgE levels, but not IgE anti-KLH levels, were increased. In the KO mice, the serum IgG1, IgG2a, IgE anti-KLH, and total IgE levels were significantly lower than those of WT mice. Surprisingly, Pb significantly enhanced IgG1 and IgG2a anti-KLH levels in the KO mice. However, for these mice, unlike the WT mice, Pb caused a greater percentage change in IgG2a than in IgG1 anti-KLH, indicating less skewing toward type-2 immunoglobulins. Lead also enhanced the delayed-type hypersensitivity (DTH) response in WT mice. Not surprisingly, very low DTH occurred in the KO mice; however, Pb induced a strong KLH-specific DTH response. The in vivo Pb exposure significantly increased in vitro production of IL-4, IL-5, and IL-10, but not IFNgamma, IL-2 and IL-12, by KLH-induced WT and KO spleen cells. In contrast to KLH, dinitrofluorobenzene contact hypersensitivity (DNFB CHS) was detected in all groups, and Pb did not affect this response, which suggests that Pb has only a slight effect on CD8+ T cell-related responses. As previously reported, Pb enhances Th2 responses in WT mice; however, in the KO mice, Pb enhanced Th1-related anti-KLH production and a Th2-related DTH. The Pb enhancement of DTH in IFNgamma-deficient mice is likely due to promotion of type-2 cytokines and enhancement of major histocompatibility complex (MHC) class II expression.     

Studies on the effects of pharmacological agents on antigen-induced arthritis in BALB/c mice

The model of antigen-induced monoarticular arthritis in BALB/c mice, originally described by Brackertz et al. (1), has been examined with regard to disease pathogenesis and the activities of established antirheumatic agents. The acute phase of the arthritis, up to 7 days after intra-articular (IA) challenge, was characterized by intense polymorphonuclear leukocyte infiltration into the challenged joint, synovial lining cell hypertrophy and hyperplasia, accumulation of mononuclear cells within the subsynovial tissue, and pannus formation. Erosions of articular cartilage and bone commenced 7-14 days after IA challenge and progressed with time. Chronic synovitis was still evident 56 days after IA challenge. Prednisolone at 1 and 5 mg/kg, when administered against an established arthritis (dosing days 14-42), suppressed the histopathological changes. A similar level of suppression was observed when prednisolone was administered from days 0-42, indicating that the drug had no additional effect on the development phase of the arthritis. The non-steroidal anti-inflammatory agents (NSAIAs) indomethacin, ibuprofen and flurbiprofen failed to suppress either the established or developing disease. Daily treatment with D-penicillamine, tiopronin or chloroquine on days 14-42 had no significant effect on the arthritis; treatment with either D-penicillamine or chloroquine on days 0-56 was also ineffective. When administered on days 14-42 or 0-42 neither gold thiomalate nor auranofin were able to suppress the erosive changes. Sulphasalazine (10-30 mg/kg) suppressed the arthritis whereas sulphapyridine was inactive. Azathioprine (20 mg/kg) suppressed the erosive changes when administered over days 14-42 or 0-42; this activity was associated with toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)     

罗红霉素治疗细菌性感染临床疗效观察

用印度Ｔｏｒｒｅｎｔ公司所生产的罗红霉素治疗细菌性感染共６０例，进行开放性临床试验。罗红霉素剂量为１５０ｍｇ，每日２次，疗程７～１４ｄ。结果总有效率为９１．７％（５５／６０），其中呼吸道感染、泌尿生殖道感染、皮肤软组织感染有效率各为９１．４％、９１．７％和１００％。细菌清除率为８８％。４例（６．７％）有轻度不良反应，其中１例为轻度皮疹，３例为胃肠道反应。本研究证明罗红霉素有较好的临床效果，可用以治疗敏感菌引起的轻、中度感染