目的:探究活动期溃疡性结肠炎(UC)寒热错杂证患者寒热偏盛不同之间肠道菌群结构的差异性.方法:39例UC寒热错杂证患者分为偏寒组19例,偏热组20例,收集两组患者粪便标本,利用16S rDNA高通量测序技术研究分析两组之间肠道菌群的差异性.结果:活动期UC寒热错杂证寒热不同偏盛两组患者之间肠道菌群的物种多样性与物种丰富度之间差异无统计学意义;但在微生物群落构成之间存在一定的差异(P＜0.05).门水平上偏寒组可能以变形菌门所占比例为主,偏热组可能以拟杆菌门所占比例为主;其他水平上偏寒组可能以埃希氏菌-志贺氏菌属所占比例为主,偏热组可能以拟杆菌目所占比例为主.结论:活动期UC寒热错杂证患者寒热不同偏盛之间可能存在代表寒热不同偏盛的菌种.

目的 探讨青黛从抑制中性粒细胞迁移浸润结肠的角度,治疗溃疡性结肠炎(UC)的作用机制.方法 选取C57BL/6小鼠40只,分为空白组、模型组、青黛组和阳性药组,每组各10只.用葡聚糖硫酸钠(DSS)诱导小鼠UC急性模型.造模7d后给药,再连续给药7d后麻醉处死.记录疾病活动指数评分、组织病理学观察结肠黏膜病理变化及中性粒细胞浸润情况;流式细胞术检测结肠固有层及肠系膜淋巴结中性粒细胞比例;ELISA检测结肠组织中的肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)及髓过氧化物酶(MPO)含量.结果 病理观察青黛组及阳性药组可见黏膜屏障修复,中性粒细胞浸润减少;青黛组肠固有层中性粒细胞比例较模型组明显降低,而肠系膜淋巴结中中性粒细胞较模型组比例升高;青黛组结肠TNF-α、IL-6及MPO含量较模型组明显下降(均P＜ 0.05或P＜0.01).结论 青黛能够减少中性粒细胞向肠固有层的迁移浸润,增加肠系膜淋巴结中中性粒细胞比例,显著降低炎性因子TNF-α、IL-6和MPO表达从而发挥抗炎、促进组织修复而治疗UC的作用.

痞满乃因气机升降失常,中焦气机壅滞为病,升为阳,降为阴,升降失常即阴阳失调,与否卦象之义同.通过扭转乾坤,即调整阴阳,将否卦爻为泰卦,将脾胃功能恢复至阴阳平衡的状态则是治疗痞满的根本目的.李军祥教授认为造成"气机不通"的病因病机各异,不能仅着眼于气机升降本身.因此,治疗痞满一病,以恢复气机正常升降为基本,通过燮理脾胃升降、纳运、润燥、寒热、气血之阴阳,从而达到阴阳平衡的状态,即泰卦之象.

目的:观察清肠温中方对缓解期溃疡性结肠炎患者维持缓解、预防复发的疗效以及用药安全性,为临床广泛应用提供科学依据.方法:采用前瞻性研究的方法,纳入缓解期溃疡性结肠炎患者50例,予清肠温中方治疗(1剂/d),治疗1年,患者每2个月接受随访,填写中医证候积分量表、生存质量积分表.治疗满1年时接受肠镜检查,患者纳入研究时及治疗满1年时均行安全性检查.结果:接受清肠温中方治疗1年后,患者维持缓解率为81.4％.治疗期间,患者便溏、腹痛、腹胀、食少、肢体倦怠、神疲懒言的症状较治疗前明显改善(P＜0.05或P＜0.01);患者的生存质量包括肠道症状、社会能力、情感能力、全身症状较治疗前明显提高(P＜0.05或P＜0.01).结论:清肠温中方能够有效维持缓解期溃疡性结肠炎的长期缓解,显著改善患者腹痛、便溏、腹胀、食少等临床症状,提高生存质量,且无明显不良反应.

目的 探讨青黛通过影响GPR41/43信号通路调控溃疡性结肠炎大鼠Treg/Th17免疫平衡的机制.方法 将24只健康的SPF级雄性SD大鼠随机分为空白组、模型组与青黛组.模型组和青黛组大鼠自由饮用4.5％DSS溶液以制备结肠炎模型,空白组自由饮用去离子水作为对照,同时青黛组大鼠给予青黛(600 mg/kg)灌胃,模型组、空白组大鼠给予去离子水处理,每天观察大鼠一般情况,记录体质量、粪便性状,检测粪便潜血,计算疾病活动指数,干预7 d,麻醉后处死大鼠,取血及结肠组织.RT-qPCR法检测结肠RORγt mRNA、Foxp3 mRNA的表达;Western Blotting法检测结肠GPR41、GPR43、RORγt、Foxp3蛋白的含量,ELISA法检测血清IL-10、IL-17水平.结果 与空白组相比,DSS诱导的结肠炎大鼠结肠GPR41、GPR43、FOXP3,血清IL-10的表达明显降低(P＜0.05或P＜0.01),结肠RORγt、血清IL-17表达明显升高(P＜0.05或P＜0.01);青黛干预后,大鼠结肠GPR41、GPR43、FOXP3、FOXP3 mRNA,血清IL-10的表达较模型组明显升高(P＜0.05或P＜0.01),结肠RORγt、RORγt mRNA、血清IL-17表达较模型组明显降低(P＜0.05).结论 青黛能够上调GPR41、GPR43的表达,进而调节Treg/Th17免疫平衡治疗溃疡性结肠炎.

Inflammatory bowel disease (IBD), a group of multifactorial and inflammatory infirmities, is closely associated with dysregulation of gut microbiota and host metabolome, but effective treatments are currently limited. Qingchang Wenzhong Decoction (QCWZD) is an effective and classical traditional herbal prescription for the treatment of IBD and has been proved to attenuate intestinal inflammation in a model of acute colitis. However, the role of QCWZD in recovery phase of colitis is unclear. Here, we demonstrated that mice treated with QCWZD showed a faster recovery from dextran sulfate sodium (DSS)-induced epithelial injury, accompanied by reduced mucosal inflammation and attenuated intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing compared to those receiving sterile water. The protective effects of QCWZD are gut microbiota dependent, as demonstrated by fecal microbiome transplantation and antibiotics treatment. Gut microbes transferred from QCWZD-treated mice displayed a similar role in mucosal protection and epithelial regeneration as QCWZD on colitis in mice, and depletion of the gut microbiota through antibiotics treatments diminished the beneficial effects of QCWZD on colitis mice. Moreover, metabolomic analysis revealed metabolic profiles alternations in response to the gut microbiota reprogrammed by QCWZD intervention, especially enhanced tryptophan metabolism, which may further accelerate intestinal stem cells-mediated epithelial regeneration to protect the integrity of intestinal mucosa through activation of Wnt/β-catenin signals. Collectively, our results suggested that orally administrated QCWZD accelerates intestinal mucosal healing through the modulation of dysregulated gut microbiota and metabolism, thus regulating intestinal stem cells-mediated epithelial proliferation, and hold promise for novel microbial-based therapies in the treatment of IBD.

目的 探讨虎地肠溶胶囊对溃疡性结肠炎(UC)小鼠黏液屏障功能的保护作用.方法 20只雌性C57BL/6小鼠随机分为空白组、模型组、虎地肠溶胶囊组以及美沙拉嗪组.除空白组外,其余小鼠连续7 d采用2.5％葡聚糖硫酸钠(DSS)溶液构建UC模型,同时,各组小鼠以相应药物灌胃干预,空白组和模型组灌胃灭菌蒸馏水.末次给药后取结肠组织,HE染色观察结肠组织病理变化,ELISA测定小鼠血清白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)含量,AB-PAS染色观察结肠黏膜中杯状细胞形态、数量.结果 与空白组比较,模型组小鼠疾病活动指数(DAI)评分显著下降(P＜0.01);结肠黏膜上皮损伤并可见黏膜以及黏膜下层炎性细胞的浸润;血清IL-6、TNF-α表达量显著升高(P＜0.05);黏膜上皮杯状细胞形态、数量有显著差异;结肠长度显著缩短(P＜0.01).与模型组比较,美沙拉嗪组、虎地肠溶胶囊组DAI评分有明显改善(P＜0.01),结肠组织损伤明显改善,血清IL-6、TNF-α表达量显著下降(P＜0.01),结肠长度明显增长(P＜0.05).虎地肠溶胶囊组黏膜上皮杯状细胞数量显著增加,细胞形态明显改善;美沙拉嗪组增加不明显.结论 虎地肠溶胶囊能够促进杯状细胞的生长,修复肠黏液屏障;抑制炎性细胞因子的表达,改善肠道炎症,缓解肠黏膜损伤,从而达到治疗溃疡性结肠炎的目的.

目的:基于古今医案云平台系统分析李军祥教授治疗溃疡性结肠炎的用药规律.方法:随机收集近2年来李军祥教授有效治疗的171例溃疡性结肠炎患者中药处方(一患一方,不分首诊及复诊),将171份处方录入到古今医案云平台系统中,经过医案标准化处理后,建立标准化的数据库,通过频数统计以及数据挖掘方法,分析方剂数据库中各中药用药频率、四气、五味、归经分布及药物功效分布,以明确李军祥教授治疗溃疡性结肠炎的诊疗思路.结果:所采集的171张处方中,涉及药物112种,其中使用频次超过110次的药物有18种;运用关联法则分析药对得到核心处方:木香、苦参、黄连、炮姜、白术、青黛、炙甘草、陈皮、地榆炭、三七、白及、白芍;用药以寒、温两性为主,味多属苦、辛、甘,药物主归脾、胃、肝、大肠、肺、肾经.所用药物主要功效以清热祛湿、清热解毒、温脾补肾、凉血化瘀、行气活血为主.结论:从用药、性味归经、功效主治上体现了李军祥教授治疗溃疡性结肠炎时以脾胃为中心,兼及五脏论治;清温并用,注重阴阳平调;重视清热祛湿解毒,不忘调畅气与血;注重整体辨证论治以提高临床疗效.

Background: Hudi enteric-coated capsule (HDC) is a Chinese medicine prescribed to treat ulcerative colitis (UC).However, its anti-inflammatory active ingredients and mechanisms remain unknown.This study aimed to investigate the active components of HDC and explore its potential mechanisms against UC by integrating network pharmacology and experimental verification.Methods: A DSS-induced colitis murine model was established to validate the efficacy of HDC by detecting disease activity index (DAI) and histopathological changes.Network pharmacological analysis was performed to identify the active compounds and core targets of HDC for the treatment of UC.The main compounds in HDC were identified by highperformance liquid chromatography.The relative expressions of HDC's core targets were also determined in vivo.Finally, molecular docking was applied to model the interaction between HDC and target proteins.Results: In an in vivo experiment, HDC, especially the middle-dose HDC, effectively reduced clinical symptoms of UC, including weight loss, bloody stool, and colon shortening.Besides, the severity of colitis was considerably suppressed by HDC as evidenced by reduced DAI scores.A total of 118 active compounds and 69 candidate targets from HDC closely related to UC progression were identified via network pharmacology.Enrichment analysis revealed that the key targets of HDC correlated with the expressions of PTGS2, TNF-α, IL-6, and IL-1β.Meanwhile, these cytokines were enriched in various biological processes through the IL-17/JAK2/STAT3 signaling pathway.The middle-dose HDC contributed more to ameliorating DSS-induced colitis through this signaling pathway than other dosages.Nine components binding to JAK2, STAT3, IL-17 and IL-6 were identified by molecular docking, confirming again the inhibition effects of HDC on the IL-17/JAK2/ STAT3 signaling pathway. Conclusion:The HDC treatment, particularly the middle-dose, exerted an anti-UC effect in a multi-component, multi-target, and multi-mechanism manner, especially inhibiting the IL-17/ JAK2/STAT3 signaling pathway to downregulate the secretion of proinflammatory cytokines.

2018年9月13日在重庆召开中华中医药学会团体标准指南第三次专家论证会,形成《消化系统常见病胃食管反流性病中医诊疗指南(基层医生版)》终稿.前期编写、修改流程见参考文献[1]. 胃食管反流病(gastroesophageal reflux disease,GERD)是临床的常见病、多发病.中华医学会消化病分会曾于2014年组织制定了《2014年中国胃食管反流病专家共识意见》,对胃食管反流病的诊疗起到了一定的规范作用.近年来,随着人们对胃食管反流病认识的提高和内镜与病理诊断技术的进步,有必要对该病的诊疗指南进行修订和更新.

目的 从细胞骨架破坏、炎症反应和缺氧环境角度开展清肠温中方的拆方研究,阐明该方在溃疡性结肠炎(ulcerative colitis,UC)治疗中,针对不同病机更加有效的药物组成单元,为其药物配伍和临床应用提供科学依据.方法 79只SD大鼠随机分10组,其中空白组7只,模型组、温中健脾组、清热燥湿组、凉血化瘀组、温中健脾合清热燥湿组、温中健脾合凉血化瘀组、清热燥湿合凉血化瘀组、全方组和美沙拉秦组,每组8只.除空白组外,其余大鼠连续7天自由饮用4％葡聚糖硫酸钠(dextran sulfate sodium,DSS)溶液以建立急性UC模型.随后7天按不同分组灌胃给药,与此同时,除空白组外的所有大鼠,仍继续饮用1％DSS溶液以维持小剂量刺激引起的病变.通过组织学病变评分、结肠低氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)蛋白电泳、波形蛋白(vimentin,VIM)和角蛋白8(cytokeratin 8,K8)免疫组化染色、血清干扰素γ诱导蛋白10(interferon-γ-inducible protein 10,IP10)、趋化因子受体3(chemokine receptor 3,CXCR3)Elisa检测,开展清肠温中方拆方的拆方研究.结果 与模型组相比,清热燥湿、温中健脾合清热燥湿、温中健脾合凉血化瘀和全方组能明显降低组织学病变评分(P<0.05).全方及拆方各组均能降低结肠中VIM/K8蛋白表达比值,其中以温中健脾合凉血化瘀组效果更明显(P<0.05).全方及拆方各组均能减少血清中IP10含量,温中健脾合凉血化瘀和温中健脾合清热燥湿组效果更为明显(P<0.05);除凉血化瘀组外各组均能降低血清CXCR3含量,其中以清热燥湿合凉血化瘀和温中健脾合凉血化瘀组降低更多,且联合组疗效优于美沙拉秦(P<0.05).全方及拆方各组均能减少结肠中HIF-1α表达,以温中健脾合凉血化瘀、温中健脾合清热燥湿和全方组的下降趋势更明显,但各组间不存在统计学差异.结论 清肠温中方全方的作用优于温中健脾合凉血化瘀和温中健脾合清热燥湿组,而两组又比单用温中健脾、清热燥湿或凉血化瘀有更明显的调控作用.进一步证实了在UC的治疗中,清热燥湿或凉血化瘀的祛邪治法,只有在联合了温中健脾的扶正药物后,才能更好地发挥修复细胞骨架、减轻炎症反应和改善缺氧环境的作用.提示在UC的临床治疗中,需要重视顾护正气,即温中健脾,才能取得更好的疗效.

功能性便秘(Functional constipation,FC)是常见的肠道功能性疾病,研究表明其发病与盆底肌协调障碍、肛门内括约肌功能障碍、肠道神经系统病变、肠道菌群失调等有关.随着微生物研究技术的发展,肠道微生态多样性与FC的相关性成为临床研究的热点,逐渐揭示了肠道微生态在FC中的重要作用.本文结合FC患者肠道微生态的变化,对微生态制剂(益生菌、益生元、合生元)、粪菌移植和中医药治疗FC的研究及其作用机制作一综述,以期为FC的治疗及后续研究方向提供参考.

Ulcerative colitis is a gastrointestinal disorder intricately associated with intestinal dysbiosis, but effective treatments are currently limited. Indigo naturalis, a traditional Chinese medicine derived from indigo plants, has been widely used in the treatment of ulcerative colitis. However, the specific mechanisms have not yet been identified. Accordingly, in this study, we evaluated the effects and mechanisms of indigo naturalis on dextran sulfate sodium (DSS)-induced colitis in rats. Our results showed that indigo naturalis potently alleviated DSS-induced colitis in rats, and reversed DSS-induced intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing. The protective effects of indigo naturalis were gut microbiota dependent, as demonstrated by antibiotic treatments and fecal microbiota transplantation. Depletion of the gut microbiota through a combination of antibiotic treatments blocked the anti-inflammatory effect of indigo naturalis on the DSS-induced colitis, and the recipients of the gut microbiota from indigo naturalis-treated rats displayed a significantly attenuated intestinal inflammation, which was actively responsive to therapeutic interventions with indigo naturalis. Notably, supplement with indigo naturalis greatly increased the levels of feces butyrate, which was positively correlated with the relative abundances of Ruminococcus_1 and Butyricicoccus. We further showed that indigo naturalis-dependent attenuation of colitis was associated with elevated expression of short-chain fatty acid-associated receptors GPR41 and GPR43. Collectively, these results suggested that indigo naturalis alleviates DSS-induced colitis in rats through a mechanism of the microbiota-butyrate axis, particularly alterations in Ruminococcus_1 and Butyricicoccus abundances, and target-specific microbial species may have unique therapeutic promise for ulcerative colitis.

Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by a relapsing-remitting course owing to recurrent intestinal inflammation. UC often has symptoms such as intermittent rectal bleeding, diarrhea, and abdominal pain. As the precise etiology of UC has not completely clarified, UC has become a public health challenge worldwide. According to an epidemiological survey, there were about 350,000 new cases of IBD in China from 2005 to 2014. By 2025, the number of IBD patients in China will reach 1.5 million. Traditional Chinese medicine (TCM) has been widely used to treat UC in China, however, it is still challenging to systematically determine the efficacy of in UC. Therefore, this trial aims to evaluate the clinical efficacy and safety of CHM in the treatment of mild active UC patients. Methods: A multi-center, double-blinding, double-dummy, active-controlled, randomized trial will be established. A total of 240 patients in 6 centers with mild active UC (Mayo score is 3-5 points) and TCM syndrome of damp-heat stasis blocking and spleen-qi deficiency will be randomly allocated in the ratio of 1:1 to 2 groups: the experimental group and the control group. The experimental group will receive Hudi enteric-coated capsules (HEC) and enteric-coated mesalazine tablets placebo; the control group will receive enteric-coated mesalazine tablets and HEC placebo. Each group will be treated for 8 weeks. The primary therapeutic outcome: the rate of clinical efficacy and clinical remission at 8 weeks of treatment (last survey point) according to the modified Mayo score. The secondary outcomes: individual symptom score, TCM syndrome score, endoscopic response rate, mucosal healing rate, and quality of life scale score. Outcomes will be assessed at baseline and the end of the trial. Besides, intestinal mucosa, stools and blood biopsies from the mild active UC patients before and after treatment will be collected to reveal the underlying mechanisms. Discussion: The results of this trial will provide compelling evidence of the efficacy and safety of HEC for treatment of mild active UC and preliminarily show the potential mechanism of how HEC acts. Finally, it will widen treatment options for patients with mild active UC.

Heweijiangni decoction (HWJND) is an effective traditional Chinese medicine prescription in clinical treatment of nonerosive reflux disease (NERD). Esophageal hypersensitivity and acid contribute to the disease. However, the exact underlying mechanism of action remains unclear. In this study, we observed the effect of HWJND on esophageal morphology in a rat model of ovalbumin (OVA)-induced visceral hypersensitivity followed by acid exposure. Esophageal morphology was assessed by measuring the extent of dilated intercellular spaces (DIS), desmosome disruption, and mitochondrial fragmentation. HWJND in low, moderate, and high doses relieved DIS and desmosome disruption in esophageal epithelium compared with model group (P<0.05 for all doses). In addition, HWJND in high dose protected mitochondria from fragmentation (P<0.05). Other findings suggest that DIS and mitochondrial fragmentation are independent events, and that omeprazole protects mitochondria. Overall, HWJND significantly resists esophageal morphology changes in OVA-induced and acid exposure rat model.

目的 研究清肠温中方调控DSS诱导溃疡性结肠炎(UC)大鼠Th17/Treg免疫平衡及肠黏膜屏障的作用机制.方法 24只SPF级雄性SD大鼠,按体质量依照随机数字表将其随机分为空白组、模型组、清肠温中方组.空白组自由饮用去离子水,同时予去离子水灌胃;模型组和清肠温中方组自由饮用4.5％ DSS溶液制备UC模型,同时模型组给予去离子水,清肠温中方组予清肠温中方灌胃.7d后麻醉大鼠后取血及结肠组织,应用Real time-PCR法检测结肠miR-675-5p、VDR mRNA、RORγt mRNA、Foxp3 mRNA的表达,ELISA法检测血清IL-10、IL-17的表达,免疫组织化学法检测ZO-1、Occludin的蛋白表达及分布.结果 与空白组比较,DSS诱导的UC大鼠结肠miR-675-5p、RORγt mRNA及血清IL-17的表达较空白组明显升高(P＜ 0.05或P＜0.01),VDR mRNA、Foxp3 mRNA、ZO-1、Occludin、血清IL-10的表达较空白组明显降低(P＜ 0.05或P＜0.01);清肠温中方干预后,大鼠结肠miR-675-5p、RORγt mRNA、血清IL-17的表达较模型组明显降低(P＜0.05),VDR mRNA、Foxp3 mRNA、ZO-1、Occludin、血清IL-10的表达较模型组明显升高(P＜ 0.05或P＜0.01).结论 清肠温中方可能通过降低miR-675-5p的表达,靶向调控VDR信号通路,从而调控溃疡性结肠炎Th17/Treg免疫平衡、修复肠黏膜屏障损伤,达到治疗UC的目的.

目的 观察清肠温中方联合粪菌移植对葡聚糖硫酸钠(DSS)诱导的溃疡性结肠炎(UC)大鼠肠黏膜的保护作用以及作用机制.方法 将48只SD大鼠适应性饲养7d后随机分为供菌组、干预组,其中供菌组大鼠(8只)正常进食饮水,每天早上10点采集新鲜粪便,制作粪便滤液.干预组大鼠(40只)随机分为5组:空白组、模型组、中药组、粪菌移植组、联合组.空白组自由饮用去离子水,同时予去离子水(1 mL/100 g)灌胃,模型组、中药组、粪菌移植组、联合组给予4.5％ DSS溶液自由饮用7d制备UC模型,同时于下午2点分别给予去离子水(1 mL/100 g)、清肠温中方(1 mL/100 g)、粪便滤液(1 mL/100 g)、清肠温中方(1 mL/100 g)联合粪便滤液(1 mL/100 g)进行灌胃.各组干预治疗7d,每日测量大鼠体质量,检测大鼠粪便潜血、记录粪便性状,计算大鼠疾病活动指数(DAI).干预结束后麻醉大鼠,腹主动脉取血,取结肠组织,光镜下观察大鼠结肠病理损伤并进行结肠组织病理学(HS)评价,化学比色法检测髓过氧化物酶(MPO)的活性,ELISA检测血清白细胞介素-6(IL-6)、转化生长因子-β(TGF-β)的表达.结果 与空白组相比,模型组大鼠毛色、活动度、粪便潜血、粪便性状等一般情况较差,DAI最大,病理损伤明显,HS评分最重,血清IL-6、TGF-β,结肠MPO的表达水平明显升高.经过干预,中药组、粪菌移植组、联合组大鼠上述指标均有不同程度的好转,并下调血清IL-6、TGF-β,结肠MPO的表达,差异均有统计学意义(P＜0.05或P＜0.01).在改善粪便潜血方面,联合组显著优于中药组及粪菌移植组(P＜ 0.05或P＜ 0.01).结论 清肠温中方、粪菌移植以及两者联合应用均可明显缓解DSS诱导UC大鼠的症状,并可通过下调IL-6、TGF-β的表达而发挥作用,且联合应用效果在改善便血方面优于两者单独应用,中西医结合势必将成为未来UC的治疗方向.

目的 探讨和胃降逆方对非糜烂性反流病(NERD)大鼠血清P物质(SP)、降钙素基因相关肽(CGRP)、特异性激活蛋白激酶2(PAR2)及食管黏膜组织中肥大细胞类胰蛋白酶(MCT)表达的影响.方法 采用随机数字表法将48只无特定病原体级雄性Sprague Dawley大鼠分为空白组、模型组、奥美拉唑组、和胃降逆配方颗粒组(配方颗粒组)、和胃降逆方水煎剂组(水煎剂组)及和胃降逆方颗粒剂高、中、低剂量组(颗粒剂高、中、低剂量组),每组6只.模型组、奥美拉唑组、配方颗粒组、水煎剂组及和胃降逆方颗粒剂高、中、低剂量组大鼠腹腔注射卵清蛋白和氢氧化铝佐剂混悬液,构建内脏高敏感性NERD大鼠模型;空白组大鼠腹腔注射等量生理盐水;24 h后,奥美拉唑组、配方颗粒剂组、水煎剂组及和胃降逆方颗粒剂高、中、低剂量组大鼠按照10 mL·kg-1分别给予840 mg·L-1奥美拉唑溶液、850 g·L-1和胃降逆配方颗粒溶液、850 g·L-1和胃降逆方水煎剂溶液及440、220、140 g·L-1和胃降逆方颗粒剂溶液灌胃,空白组、模型组大鼠给予10 mL·kg-1的蒸馏水灌胃,每日1次,连续2周.灌胃后第14天,模型组及各干预组大鼠给予弱酸食管滴注,空白组大鼠给予蒸馏水食管滴注,然后处死大鼠,取血清及食管黏膜组织;苏木精·伊红染色观察大鼠食管黏膜鳞状上皮层病理变化,酶联免疫吸附试验法检测大鼠血清SP、CGRP、PAR2的表达,免疫组织化学法检测大鼠食管黏膜组织中MCT的表达.结果 空白组大鼠食管黏膜鳞状上皮细胞间隙紧密,无明显炎性细胞浸润、鳞状上皮层增生等表现;模型组大鼠食管黏膜鳞状上皮细胞间隙明显增宽,鳞状上皮层存在少量炎性细胞浸润,乳突出现一定延长;奥美拉唑组及各中药干预组大鼠可见增宽的细胞间隙不同程度减小或恢复,炎性细胞及鳞状上皮层增生均不明显.与空白组比较,模型组大鼠血清SP、CGRP蛋白表达水平和食管黏膜组织中MCT相对表达量显著升高(P＜0.01),2组大鼠血清PAR2蛋白表达水平比较差异无统计学意义(P＞0.05).与模型组比较,奥美拉唑组、颗粒中剂量组大鼠血清SP蛋白表达水平下降(P＜0.05),其余各用药组大鼠血清SP蛋白表达水平与模型组比较差异无统计学意义(P＞0.05).与模型组比较,奥美拉唑组及颗粒剂高、中剂量组大鼠血清CGRP蛋白表达水平显著下降(P＜0.01),其余各用药组大鼠血清CGRP蛋白表达水平与模型组比较差异无统计学意义(P＞0.05).与模型组比较,颗粒剂高剂量组大鼠血清PAR2蛋白表达水平升高(P＜0.05),其余各用药组大鼠血清PAR2蛋白表达水平与模型组比较差异无统计学意义(P＞0.05).与模型组比较,奥美拉唑组、水煎剂组及颗粒剂中、低剂量组大鼠食管黏膜组织中MCT相对表达量显著降低(P＜0.01),配方颗粒剂组、颗粒剂高剂量组大鼠食管黏膜组织中MCT相对表达量与模型组比较差异无统计学意义(P＞0.05).其余各用药组大鼠血清SP蛋白表达水平与奥美拉唑组比较差异无统计学意义(P＞0.05).水煎剂组和颗粒剂低剂量组大鼠血清CGRP蛋白表达水平高于奥美拉唑组(P＜0.05,P＜0.01),其余各用药组大鼠血清CGRP蛋白表达水平与奥美拉唑组比较差异均无统计学意义(P＞0.05).和胃降逆方各用药组大鼠血清PAR2蛋白表达水平与奥美拉唑组比较差异均无统计学意义(P＞0.05).配方颗粒剂组、颗粒剂高剂量组大鼠食管黏膜组织中MCT相对表达量与奥美拉唑组比较显著增高(P＜0.01);水煎剂组及颗粒剂中、低剂量组大鼠食管黏膜组织中MCT相对表达量与奥美拉唑组比较差异无统计学意义(P＞0.05).结论 和胃降逆方可抑制大鼠食管黏膜组织中肥大细胞激活,降低血清神经肽类物质SP、CGRP表达,一定程度减轻NERD大鼠食管黏膜组织炎性增生及细胞间隙增宽状态,从而调整内脏高敏感状况;其中220 g·L-1和胃降逆方颗粒剂对NERD大鼠的改善效果最佳.

溃疡性结肠炎(ulcerative colitis,UC)是一种累及直肠和结肠慢性非特异性炎症性疾病,临床以腹痛、腹泻、黏液脓血便、里急后重为主要临床表现[1],该病病程较长,日久可出现关节炎、虹膜炎、原发性硬化性胆管炎、骨质疏松、贫血等肠外表现[2],严重影响患者的生活质量.其病变范围广、呈连续性和弥漫性分布,如未能进行积极治疗,可并发中毒性巨结肠、肠穿孔、下消化道大出血及癌变等并发症.

[目的]观察健胃消食口服液对脾虚食滞型老年人功能性消化不良(FD)患者的临床疗效.[方法]将240例FD患者随机分为试验组120例,对照组120例,由4家中心分别承担.试验组健胃消食口服液,口服,每次1支,1日3次,对照组消化酶片,口服,每次3片,1日3次.服药4周后,观察2组临床疗效.[结果]2组最终纳入229例受试者,试验组114例,对照组115例,与本组治疗前比较,2组治疗后脘腹胀满、疲乏无力、嗳腐吞酸、暖气倒饱、恶心呕吐、食欲不振、大便稀溏症状有明显改善(P＜0.01),2组治疗后各项评分及疗效比较,差异有统计学意义(P＜0.01).[结论]健胃消食口服液能够明显改善老年人FD的临床症状,提高患者生活质量.