肠道细菌CGC定植及其对局部细胞活性的影响

目的:探讨肠道细菌CGC在体内定植分布的主要位置及这种定植对局部细胞活性的影响.方法:采用头孢呋辛钠诱导CGC产生,以体内细菌定植的原位检测方法对结肠各段CGC定植情况进行检测.在建立了IBS动物模型基础上,采用高效液相色谱法对CGC定植较多的回盲部肠黏膜上皮细胞的腺苷酸能荷及ATP与腺苷酸库比值进行测定,以反映细胞活性状态.结果:正常大鼠检测未见大量细菌CGC,在模型鼠标本的连续检测结果中检出大量CGC.通过肠道细菌定植检测,细菌CGC主要定植在回盲部和升结肠段;与正常组相比,IBS模型组回盲部三个肠段的细胞线粒体ATP能荷值以及ATP与总腺苷酸库比值检测结果明显降低,相应肠段之间数值差异显著(均P<0.05).结论:细菌CGC在大鼠体内定植显优势分布,在局部定植后能引起细胞活性降低.     

细菌潜生体相关的IBS动物模型建立实验研究

目的：建立一种新的IBS动物模型。方法在CGC与IBS发病相联系的临床调查基础上,建立CGC定植相关的IBS动物模型,判断指标选择了动物体内的CGC定植状况、粪便含水量、排便次数、结肠肌电特征、张力改变以及肠道组织的病理切片观察。结果上述指标在模型动物中均有特定的改变,并分别地反映出病人的腹泻特征,肠道动力异常改变特征及无明显病理损伤特征,同时在发病的特点上也显示出体内细菌CGC定植,反复应用抗生素以及反复发作的特征,并且建模阳性率在45%～50%之间。结论本文所建立的模型在与临床的相似性及模型本身的重复性方面均达到了要求,是一种理想的IBS动物模型,可以为IBS的研究提供一个新的更为合理的实验基础。     

富血小板血浆与抗生素联合应用在抑制大肠埃希菌中的作用

目的:探究富血小板血浆(platelet-rich plasma, PRP)及其与抗生素头孢呋辛钠联合应用在体外对大肠埃希菌的作用。方法:从六安市中心血站获取健康志愿者捐献的血小板作为PRP来源。将一定浓度的大肠埃希菌质控菌株与PRP及抗生素头孢呋辛钠共同培养，观察PRP单独应用及与抗生素头孢呋辛钠联合应用时的抑菌情况。结果:2 mg/L头孢呋辛钠在12 h内无抑菌作用，4 mg/L头孢呋辛钠可在24 h内发挥抑菌作用，8 mg/L头孢呋辛钠可在48 h内发挥较强抑菌作用。PRP单独应用可以在24 h内发挥抑菌作用，与2 mg/L头孢呋辛钠联合应用在12 h内可抑制大肠埃希菌生长，与4 mg/L头孢呋辛钠联合应用在24 h内可抑制大肠埃希菌生长，与8 mg/L头孢呋辛钠联合应用在36 h内可抑制大肠埃希菌生长。结论:PRP单独应用在体外可抑制大肠埃希菌的生长，与抗生素联合应用可发挥抑菌作用，并减轻抗生素的使用剂量。     

头孢呋辛钠联合清开灵治疗老年肺气肿合并感染的临床疗效观察

目的探究头孢呋辛钠联合清开灵治疗老年肺气肿合并感染的临床疗效。方法将2015年3月~2016年10月我院收治的老年肺气肿合并感染患者84例纳入研究,采用随机数值法,将之分为对照组和观察组,各42例,在基础治疗的基础上,对照组给予头孢呋辛钠治疗,观察组给予头孢呋辛钠联合清开灵治疗,对比两组临床疗效。结果在治疗总有效率上,观察组为95.24%,对照组为73.81%,明显低于观察组,两组数据对比差异显著(P0.05),有统计学意义。结论头孢呋辛钠联合清开灵治疗老年肺气肿合并感染,疗效显著,值得采纳应用。     

细菌潜生体相关的肠易激综合征动物模型的建立及细菌潜生体在肠易激综合征中的意义

目的:建立一种与细菌潜生体(cryptic growth cell,CGC)相关的肠易激综合征(IBS)动物模型,探讨细菌潜生体在IBS发病中的作用。方法:采用Wistar大鼠分组试验,对照组包括空白对照组、单纯灌喂辣椒液刺激组、甲砜霉素对照组(无     

头孢呋辛钠联合清开灵治疗老年肺气肿合并感染的疗效观察

目的研究头孢呋辛钠联合清开灵治疗老年肺气肿合并感染患者的疗效。方法选择2013年4月~2015年4月我院收治的老年肺气肿合并感染患者70例,将其随机分为观察组与对照组,各35例。对照组应用孢呋辛钠进行治疗,观察组应用头孢呋辛钠+清开灵进行治疗,比较两组疗效。结果观察组与对照组治疗缓解率分别为85.71%、97.14%,观察组明显高于对照组,差异有统计学意义(P0.05)。结论应用头孢呋辛钠+清开灵对老年肺气肿合并感染进行治疗,疗效更显著,值得临床推广。     

头孢呋辛钠联合中药治疗小儿腹泻的疗效观察

目的分析头孢呋辛钠联合自配中药进行小儿腹泻治疗的效果。方法选取2013年1月~2015年2月我院进行腹泻治疗患儿30例作为研究对象,将其平均分为观察组与对照组,各15例。观察组患儿单纯的采用头孢呋辛钠联合自配中药的方式来治疗,对照组的患儿则单纯采用头孢呋辛钠来进行治疗。对于两组患儿的疗效进行对比分析。结果与对照组患儿相比,观察组患儿在治疗的总有效率以及住院时间和症状改善时间等方面明显的好于对照组的患儿,差异有统计学意义(P0.05)。结论采用头孢呋辛钠联合中药联合治疗小儿腹泻具有良好的效果以及较高的临床推广价值。     

阿奇霉素治疗社区获得性肺炎的临床疗效及安全性评价

目的 评价阿奇霉素(希舒美)治疗社区获得性肺炎(CAP)的临床疗效及安全性.方法 对2005年12月至2007年6月中国医科大学附属第四医院呼吸科收治的218例CAP患者采用单盲、随机对照试验研究.将120例(单一用药组)轻中度CAP且无基础疾病患者随机分为希舒美治疗组(60例)及头孢呋辛钠对照组(60例);98例(联合用药组)重度CAP或合并基础疾病患者随机分为头孢呋辛钠联合希舒美治疗组成(50例)及头孢呋辛钠联合国产阿奇霉素对照组(48例).所有研究均以7～14d为1个疗程.观察治疗组与对照组的临床疗效、不良反应;比较体外分离出的135株细菌对希舒美、左氧氟沙星、头孢呋辛钠药敏情况.结果 单一用药组和联合用药组的临床有效率分别为93.33%和96.00%,均高于对照组78.33%、79.17%,临床症状改善及理化检查好转时间治疗组均低于对照组(P<0.05);希舒美对分离出细菌的敏感率最高77.04%,对左氧氟沙星、头孢呋辛钠耐药的菌株也有敏感性,其敏感率分别为42.31%、42.86%.希舒美对支原体所致CAP的治愈率为90.57%.不良反应发生率希舒美高于头孢呋辛钠(21.82%对16.67%),差异无统计学意义(P>0.05),主要不良反应为静脉滴注局部疼痛.结论 希舒美是治疗社区获得性肺炎安全有效的药物.     

头孢类抗生素在胆汁中药代动力学的动物实验研究

目的 测定头孢曲松钠等七种抗生素在胆灞占的药代动力学参数，为临床医生治疗胆道感染提供合理选择本组抗生素的理论基础。方法 犬为实验动物。行胆总管造瘘术，术后分别给犬静脉注射头孢曲松钠，先锋哌酮钠，头孢他啶，头孢唑啉钠，头孢拉定，头孢呋辛钠，头孢美唑等七种抗生素后，分别留取不同时间点的胆汁标本。用微生物法测定各份标本中抗生素的浓度，用3P87软件进行数据计算，得出各抗生素的药代动力学参数。结果 头孢哌酮钠在胆汁中的峰值浓度最高，为2464.7μg/ml；头孢曲松钠的半衰期最长，达3024.2min，头孢呋辛钠和头孢美唑两者在胆汁中的峰值浓度最低，分别为39.8和21.4μg/ml。半衰期也短。为69.3和102.1min，余者介于中等。结论 治疗胆道感染时，头孢曲松钠，头孢哌酮钠应为首选药，头孢唑啉钠，头孢拉定，头孢他啶次之，而头孢呋辛钠，头孢美唑不宜用于治疗胆道感染。     

注射用兰索拉唑与果糖二磷酸钠的配伍禁忌分析

目的：观察注射用兰索拉唑（ LSZ）与果糖二磷酸钠（ FDP）的药物配伍禁忌情况。方法将FDP配制液分别与头孢呋辛钠、LSZ混合配置成测定液，利用紫外分光光度计以及pH计进行分析，观察两组pH值变化、溶液外观及药品含量变化。结果经过不同配伍方式的放置后，虽然两组的pH值均发生变化，但相应的变化值差异无统计学意义（P＞0．05）。 FDP与头孢呋辛钠在放置4 h内溶液外观均为澄清，且无明显变化，但FDP与LSZ在放置0．5 h后溶液外观呈现为橘色，2 h 以后有黑色沉淀产生。放置4 h 后，LSZ 药品的含量变化值为（74．15±25．85）％，头孢呋辛钠为（98．63±1．37）％，两者比较有统计学差异（P＜0．05）。结论注射用LSZ与FDP有配伍禁忌，如需联用，应间隔用药，尽可能减少配伍禁忌。     

痛泻要方对醋酸-电刺激大鼠实验性肠易激综合征作用的研究

[目的]探讨痛泻要方对醋酸-电刺激大鼠实验性肠易激综合征（IBS）的作用及其机制。[方法]给予大鼠慢性反复直结肠灌注醋酸造成炎症刺激,炎症恢复后予小量电刺激诱发高敏感性的肠道发生应激反应,模拟人类IBS,观察痛泻要方对刺激期间大鼠排便量、粪便含水量、血浆P物质（SP）和血管活性肠肽（VIP）水平等各项指标的影响。[结果]模型组与正常组比较,大鼠排便量、粪便含水量增加（P〈0.01）,血浆SP和VIP减少（P〈0.05）;痛泻要方高剂量组与模型组比较,大鼠的排便量、粪便含水量减少（P〈0.05）,血浆SP和VIP增加（P〈0.05）。[结论]醋酸-电刺激大鼠模型可有效模拟人类IBS,痛泻要方能够改善该模型的排便加速、粪便含水量增加、血浆SP和VIP水平紊乱等症状。     

Daily Intake of High Dietary Fiber Slows Accelerated Colonic Transit Induced by Restrain Stress in Rats

Background Stress and central corticotropin releasing factor (CRF) are contributing factors to the pathogenesis of irritable bowel syndrome (IBS). It has been shown that restraint stress and central CRF stimulate colonic motility in rats. Short-chain fatty acids (SCFAs) are produced by bacterial fermentation from dietary fibers. It is controversial whether daily intake of dietary fiber is beneficial for patients with diarrhea-predominant IBS. We studied whether dietary fiber intake affects colonic transit and motility stimulated by restraint stress and central CRF in rats. Methods Corn starch is digested almost completely in the small intestine, while potato starch shows substantial resistance to α-amylase and its consumption leads to stimulation of large-bowel fermentation. Four weeks after a corn starch, potato starch, or usual diet (rat chow), colonic transit and motility stimulated by restraint stress and intracisternal (ic) injection of CRF were studied. Fecal concentration of SCFAs in the cecum was measured by high-performance liquid chromatography (HPLC). Results Four-week treatment with potato starch diet significantly increased cecal concentrations of SCFAs, compared to treatment with corn starch diet. Accelerated colonic transit induced by stress and ic injection of CRF (1 μg) were significantly attenuated in rats receiving potato starch diet compared to rats receiving corn starch diet. The incidence of unformed stool (diarrhea) induced by stress and CRF was also reduced in rats receiving potato starch diet compared to rats receiving corn starch diet and usual diet. Conclusion It is suggested that daily intake of a high-fiber diet may prevent stress- and CRF-induced acceleration of colonic transit and diarrhea. This study may contribute to treatment for the patients of diarrhea-predominant IBS.     

Altered vasoactive intestinal peptides expression in irritable bowel syndrome patients and rats with trinitrobenzene sulfonic acid-induced colitis

AIM: To investigate the vasoactive intestinal peptides(VIP) expression in irritable bowel syndrome(IBS) and trinitrobenzene sulfonic acid(TNBS) induced colitis.METHODS: The VIP gene expression and protein plasma levels were measured in adult participants(45.8% male) who met Rome Ⅲ criteria for IBS for longer than 6 mo and in a rat model of colitis as induced by TNBS.Plasma and colons were collected from naive and inflamed rats.Markers assessing inflammation(i.e.,weight changes and myeloperoxidase levels) were assessed on days 2,7,14 and 28 and compared to controls.Visceral hypersensitivity of the rats was assessed with colo-rectal distension and mechanical threshold testing on hind paws.IBS patients(n = 12) were age,gender,race,and BMI-matched with healthy controls(n = 12).Peripheral whole blood and plasma from fasting participants was collected and VIP plasma levels were assayed using a VIP peptide-enzyme immunoassay.Human gene expression of VIP was analyzed using a custom PCR array.RESULTS: TNBS induced colitis in the rats was confirmed with weight loss(13.7 ± 3.2 g) and increased myeloperoxidase activity.Visceral hypersensitivity tocolo-rectal distension was increased in TNBS treated rats up to 21 d and resolved by day 28.Somatic hypersensitivity was also increased up to 14 d post TNBS induction of colitis.The expression of an inflammatory marker myeloperoxidase was significantly elevated in the intracellular granules of neutrophils in rat models following TNBS treatment compared to naive rats.This confirmed the induction of inflammation in rats following TNBS treatment.VIP plasma concentration was significantly increased in rats following TNBS treatment as compared to naive animals(P 0.05).Likewise,the VIP gene expression from peripheral whole blood was significantly upregulated by 2.91-fold in IBS patients when compared to controls(P 0.00001; 95%CI).VIP plasma protein was not significantly different when compared with controls(P = 0.193).CONCLUSION: Alterations in VIP expression may play a role in IBS.Therefore,a better understanding of the physiology of VIP could lead to new therapeutics.     

感觉神经损伤性盐敏感性高血压大鼠血浆血管紧张素Ⅱ和内皮素的变化

目的观察感觉神经损伤性盐敏感性高血压大鼠模型血浆血管紧张素Ⅱ和内皮素-1的变化,并探讨该模型形成的可能机制。方法新生Wistar大鼠皮下注射辣椒辣素（50mg／Kg）,对照组则皮下注射对照液,哺乳期后挑选出雄性大鼠分成4组分别给予含盐不同的饮食4周,检测鼠尾收缩压、体重、血浆血管紧张素Ⅱ浓度、内皮素-1浓度和24h尿量、饮水量、尿钠、尿钾。结果辣椒辣素新生处理大鼠在高盐饮食时鼠尾收缩压明显增高,肾排钠和水功能降低、血浆血管紧张素Ⅱ和内皮素-1浓度明显升高。结论感觉神经损伤性盐敏感性高血压大鼠新模型的形成可能与肾素一血管紧张素一醛固酮及内皮素系统有关。     

Visceral hypersensitive rats share common dysbiosis features with irritable bowel syndrome patients

AIM: To evaluate gut microbial dysbiosis in two visceral hypersensitive models in comparison with irritable bowel syndrome(IBS) patients and to explore the extent to which these models capture the dysbiosis of IBS patients. METHODS: Visceral hypersensitivity was developed using the maternal separation(MS) rat model and post-inflammatory rat model. The visceral sensitivity of the model groups and control group was evaluated using the abdominal withdraw reflex score and electromyography in response to graded colorectal distention. The 16 S ribosomal RNA gene from fecal samples was pyrosequenced and analyzed. The correlation between dysbiosis in the microbiota and visceral hypersensitivity was calculated. Positive findings were compared to sequencing data from a published human IBS cohort.RESULTS: Dysbiosis triggered by neonatal maternal separation was lasting but not static. Both MS and postinflammatory rat fecal microbiota deviated from that of the control rats to an extent that was larger than the co-housing effect. Two short chain fatty acid producing genera, Fusobacterium and Clostridium XI, were shared by the human IBS cohort and by the maternal separation rats and post-inflammatory rats, respectively, to different extents. Fusobacterium was significantly increased in the MS group, and its abundance positively correlated with the degree of visceral hypersensitivity. Porphyromonadaceae was a protective biomarker for both the rat control group and healthy human controls. CONCLUSION: The dysbiosis MS rat model and the post-inflammatory rat model captured some of the dysbiosis features of IBS patients. Fusobacterium, Clostridium XI and Porphyromonadaceae were identified as targets for future mechanistic research.     

丁酸钠溶液灌肠对大鼠内脏感觉的影响

对于肠易激综合征（IBS）内脏感觉功能异常的研究，需建立合适的动物模型。目的：以丁酸钠溶液灌肠建立大鼠结肠感觉过敏模型，观察其内脏感觉功能和结肠黏膜改变。方法：16只大鼠随机分为实验组和对照组。实验组予1 ml 200mmol／L丁酸钠溶液灌肠，对照组予1 ml 0.9％NaCl溶液灌肠，每天2次，连续3d。分别于灌肠前和实验开始后第3、6、9、12、15、18d行结直肠扩张（CRD），观察腹壁回撤反射（AWR）评分和内脏感觉压力闽值，以反映内脏感觉功能。实验结束后处死大鼠，行结肠黏膜大体形态观察和组织学检查。结果：实验第3-12d．实验组不同CRD压力下AWR评分均显著高于对照组（P〈0.05），疼痛感觉压力阈值显著低于对照组（P〈0.05）；第15-18d，上述指标恢复至初始状态。实验结束后,实验组与对照组结肠黏膜大体形态和组织学改变均无明显差异。结论：丁酸钠溶液反复灌肠可诱导大鼠结肠感觉过敏，内脏感觉功能恢复后，结肠黏膜改变同步恢复。该模型可用于IBS病理生理机制的研究。     

肠易激综合征内脏感觉过敏大鼠脊髓诱发电位的研究

背景:内脏感觉过敏是肠易激综合征(IBS)的主要发病机制之一,临床上缺乏客观、无创的内脏敏感性检测方法。目的:建立直肠球囊扩张下脊髓诱发电位(SEP)的检测方法,并通过IBS内脏感觉过敏大鼠与正常大鼠的比较以及雌雄大鼠之间的比较,取得IBS存在内脏感觉过敏的客观证据。方法:通过直肠球囊有节律的充气、放气,给予直肠一定频率的反复刺激,记录诱发得到的脊髓相应节段(L6～S2)的SEP。结果:实验组雌雄大鼠分别与对照组同性别大鼠相比,SEP各波潜伏期显著缩短(P<0.05),峰间波幅显著增高(P<0.01)。实验组雌性大鼠的各波潜伏期显著短于雄性大鼠(P<0.05),峰间波幅也低于雄性大鼠(P<0.05);对照组雌性与雄性大鼠的各波潜伏期和峰间波幅无显著差异。结论:通过有节律的直肠球囊扩张,能诱发得到重复性好、易识别的SEP,可作为内脏敏感性的客观依据。     

直肠扩张刺激引起IBS大鼠痛行为学以及腹肌电活动的变化

目的观察直肠扩张刺激对IBS大鼠痛行为以及腹部肌电活动的影响,为探讨IBS发生机制提供理论依据。方法48只旋毛虫感染大鼠,随机均分为8组:空白对照组、放置气囊对照组、0.6ml组、0.8ml组、1.0ml组、1.2ml组、1.4ml组和1.5ml组。应用疼痛行为学观察方法,观察各组动物1h的痛行为学和腹外斜肌电活动变化。结果空白对照组和单纯放置气囊对照组无明显痛行为变化。正常大鼠痛行为表现最为明显的为1.2ml组(疼痛评分范围为72.66±8.75至53.67±5.84),它与1.4ml和1.5ml组的痛行为无明显差异(疼痛评分范围为68.36±6.24至48.55±6.01和70.15±6.57至47.18±6.66)。而1.0ml组大鼠的痛行为表现比1.2ml组为低(疼痛评分范围为44.16±6.34至35.11±6.27),0.8ml组的痛行为表现最低(疼痛评分范围为32.53±6.06至29.46±6.17)。实验组IBS大鼠,0.6ml时即出现明显的痛行为学表现(痛行为评分为51.55±7.57至53.23±5.46)与单纯给与气囊之对照组的痛行为(17.16±3.12至19.23±4.54)相比有显著性差异。0.8ml组的痛行为学最为明显(痛行为评分为93.53±4.07至90.33±4.79),基本上达到痛行为学反应的高峰,与0.6ml组相比,存在显著性差异,而与1.0ml组及以后各组相比无明显差异。正常大鼠中,未放置球囊及单纯直肠放置气囊组腹外斜肌电活动少而规律,1.2ml组正常大鼠腹外斜肌电活动最为明显,与1.4ml、1.5ml组相比没有显著性差异,而与其它组相比,均有显著性差异(P<0.05)。实验组IBS大鼠中,0.8ml组的腹外斜肌电活动明显有变化,基本趋于高峰,与0.6ml组有差异(P<0.05),但与1.0ml及以后各组没有显著性差异(P>0.05)。结论结肠扩张刺激明显引起IBS鼠痛行为和腹部肌电活动的变化,与其内脏敏感性增高有密切关系。     

Effect of electro-acupuncture on substance P, its receptor and corticotropin-releasing hormone in rats with irritable bowel syndrome

AIM: To investigate the effect and mechanism of electro-acupuncture (EA) at ST25 and ST37 on irritable bowel syndrome (IBS) of rats. METHODS: A total of 21 male Sprague-Dawley rats were randomly divided into normal group, model group and EA group. A rat model of IBS was established by constraining the limbs and distending the colorectum of rats. Rats in EA group received bilateral EA at ST25 and ST37 with a sparse and intense waveform at a frequency of 2/50 Hz for 15 min, once a day for 7 d as a course. Rats in normal and model groups were stimulated by distending colorectum (CR). An abdominal withdrawal reflex (AWR) scoring system was used to evaluate improvements in visceral hypersensitivity. Toluidine blue-improved method, immunohistochemistry and radioimmunoassay were used to observe mucosal mast cells (MC), changes of substance P (SP) and substance P receptor (SPR) in colon and change of corticotropin-releasing hormone (CRH) in hypothalamus. RESULTS: The threshold of visceral sense was significantly lower in model group than in normal group, and significantly higher in EA group than in model group. The number of mucosal MC was greater in model group than in normal group and significantly smaller in EA group than in model group. The CRH level in hypothalamus of rats was significantly higher in model group than in normal group, which was remarkably decreased after electro-acupuncture treatment. The SP and SPR expression in colon of rats in model group was decreased after electro-acupuncture treatment.CONCLUSION:EA at ST25 and ST37 can decrease the number of mucosal MC and down-regulate the expression of CRH in hypothalamus,and the expression of SP and SPR in colon of rats with IBS.