微米大黄炭联合三联疗法治疗幽门螺杆菌阳性活动期胃溃疡的临床观察

目的：研究微米大黄炭联合三联疗法治疗幽门螺杆菌（Hp）阳性活动期胃溃疡的临床疗效、溃疡愈合质量及对肿瘤坏死因子-α（TNF-α）、白介素-8（IL-8）的影响。方法：将72例Hp阳性活动期胃溃疡患者随机分为观察组和对照组各36例。对照组予以三联疗法根除Hp治疗2周后,给予埃索美拉唑治疗6周;观察组在对照组基础上加用微米大黄炭口服。2组总疗程均为8周。观察治疗前后2组患者的临床症状积分、Hp根除情况、内镜及组织学再生黏膜成熟度以及血清TNF-α、IL-8的变化。结果：在改善患者临床症状方面,两组临床症状积分无明显差异（P>0.05）;在内镜下再生黏膜成熟度、组织学再生黏膜成熟度、Hp根除率方面,观察组均明显优于对照组（P<0.05）;在血清TNF-α、IL-8水平方面,观察组明显低于对照组（P<0.05）。结论：微米大黄炭联合三联疗法治疗Hp阳性活动期胃溃疡可提高Hp清除率,提高再生胃黏膜成熟度,提高溃疡愈合质量,其作用机制可能与降低炎症因子TNF-α、IL-8水平相关。     

参麦注射液联合双抗治疗对老年非ST段抬高型急性冠脉综合征患者血清MMP-9、TNF-α及IL-6水平的影响

目的：探讨参麦注射液联合双抗治疗对老年非ST段抬高型急性冠脉综合征患者血清MMP-9、TNF-α及IL-6水平的影响。方法：研究对象为80例老年非ST段抬高型急性冠脉综合征患者,均接受常规治疗,对照组给予阿司匹林及氯吡格雷双抗治疗,研究组在此基础上再予参麦注射液静点,连续治疗4 d。检测治疗前、后血清炎性因子及心肌损伤标志物,胸痛发作情况及出血情况,血小板聚集率及主要心血管发生率,比较临床疗效。结果：与治疗前比较,两组血清血清肿瘤坏死因子α（tumor necrosis factor,TNF-α）、白介素-6（interleukin-6,IL-6）及C反应蛋白（C-reactionprotein,CRP）水平均显著降低（P<0.01）,肌钙蛋白T（cardiac troponin T,cTnT）、肌酸激酶同工酶（isoenzyme of creatine kinase,CK-MB）水平均明显升高（P<0.05）,基质金属蛋白酶-9（matrix metallo preteinases-9,MMP-9）水平明显降低（P<0.05）,胸痛发作频率显著降低（P<0.01）,持续时间显著缩短（P<0.01）;与对照组比较,研究组血清TNF-α、IL-6及CRP水平较低（P<0.01）,cTnT、CKMB水平较低,MMP-9水平较低（P<0.05）,胸痛发作频率较低（P<0.01）,持续时间较短（P<0.01）,血小板聚集率较低（P<0.01）,主要心血管发生率较低（P<0.01）,治疗有效率较高（P<0.01）。结论：参麦注射液联合双抗治疗老年非ST段抬高型急性冠脉综合征有显著疗效,能明显改善胸痛,且能降低血清MMP-9、TNF-α及IL-6水平。     

微米大黄炭对乙醇性急性胃黏膜损伤大鼠脂氧素A4合成途径的影响

目的:研究微米大黄炭对乙醇诱导急性胃黏膜损伤模型大鼠黏膜的保护作用及脂氧素A₄合成途径的影响。方法:将32只SD大鼠随机分为空白组、模型组、铝镁加混悬液组和微米大黄炭组，每组8只，各组分别予以相应浓度药物灌胃1 h后，采用无水乙醇法制备急性胃黏膜损伤大鼠模型，观察各组大鼠胃黏膜组织PGE₂、LXA₄、LTA₄、LTB₄水平，检测各组大鼠胃黏膜组织5-LOX、12-LOX、15-LOX及LXA₄受体FPR2的蛋白表达水平。结果:各给药组大鼠黏膜损伤指数显著低于模型组。与模型组相比，铝镁加组PGE₂、LXA₄、15-LOX表达水平显著上升，LTA₄、LTB₄表达水平均显著下降，5-LOX、12-LOX、FPR2表达水平差异无统计学意义；微米大黄炭组PGE₂、LXA₄、5-LOX、15-LOX、FPR2表达水平显著上升，LTA     

TAK-242通过调控JAK2/STAT3通路抑制小鼠心肌缺血再灌注损伤炎症反应

目的：探讨Toll样受体4拮抗剂TAK-242抑制小鼠心肌缺血/再灌注损伤（ischemia/reperfusion,I/R）炎症反应的分子机制。方法：选用48只雄性C57BL/6小鼠随机分为4组：假手术组（sham）、模型组（I_30min /R_24h）、给药组[I/R+TAK-242（3 mg·kg^-1）]、干预组[I/R+TAK-242+AG490（15 mg·kg^-1）]。再灌注24 h后心脏超声检测小鼠心功能,氯化三苯基四氮唑（TTC）染色法测定心肌梗死面积,HE染色观察心肌病理改变,WB检测心肌JAK2/STAT3磷酸化水平,ELISA检测血清IL-6、TNF-α、IL-10和高迁移率族蛋白B1（HMGB1）浓度。结果：与sham组比较,I/R组小鼠左心室收缩期直径（LVIDs）延长（P<0.01）,左心室射血分数（LVEF）和左心室短轴缩短分数（LVFS）显著降低（P<0.001或P<0.01）,心梗面积明显增加并出现心肌炎性浸润,心肌p-JAK2/p-STAT3表达明显升高（P<0.01或P<0.05）,血清IL-6、IL-10、TNF-α和HMGB1水平显著升高（P<0.001或P<0.01）。与I/R组比较,TAK-242给药组小鼠LVIDs缩短（P<0.05）,LVEF和LVFS显著升高（P<0.01或P<0.05）,心梗面积缩小（P<0.01）,心肌炎症浸润减轻,心肌p-JAK2/p-STAT3表达降低（P<0.01或P<0.05）,血清IL-6和TNF-α水平明显下降（P<0.001或P<0.01）,而IL-10和HMGB1浓度进一步升高（P<0.01）。与TAK-242给药组比较,AG490干预可显著加强TAK-242治疗作用,包括心肌收缩功能增强,心梗面积缩小及炎性浸润程度减轻,心肌p-JAK2/p-STAT3表达降低（P<0.05）,血清IL-6、TNF-α浓度下降而IL-10、HMGB1浓度升高（P<0.01或P<0.05）。结论： Toll样受体4拮抗剂TAK-242抑制小鼠I/R炎症反应与JAK2/STAT3信号通路失活有关。     

阿魏酸钠对慢性不可预知温和刺激抑郁症大鼠抑郁行为的影响及其机制

目的：研究阿魏酸钠能否改善慢性不可预知温和刺激（chronic unpredicted mild stress,CUMS）抑郁大鼠的抑郁样行为并探讨其机制。方法：将SD大鼠随机分为正常对照组、CUMS模型组、CUMS+氟西汀（10 mg· kg^-1）组、CUMS+阿魏酸钠（50,100,150 mg· kg^-1）组。采用慢性温和不可预知应激方法建立大鼠抑郁模型,造模完成后,连续灌胃给药21 d。旷场实验、糖水偏爱实验、强迫游泳实验检测大鼠的行为学变化;生物化学方法检测大鼠海马超氧化物歧化酶（superoxide dismutase,SOD）和过氧化氢酶（catalase,CAT）活性及活性氧（reactive oxygen species,ROS）含量。实时荧光定量PCR（q-PCR）法检测海马炎症因子IL-1β、TNF-α、PGE₂及IL-10基因的mRNA转录水平;酶联免疫吸附试验检测海马炎症因子IL-1β、TNF-α、PGE₂及IL-10含量的变化。结果：行为学检测结果显示,与正常对照组相比,旷场实验中模型组大鼠水平运动和垂直运动得分降低（P<0.01）,糖水偏爱实验中糖水偏爱度显著下降（P<0.01）,强迫游泳实验中不动时间明显延长（P<0.01）;分子生物学检测结果显示,模型组大鼠海马内ROS含量显著升高（P<0.01）,SOD和CAT的活性显著降低（P<0.01）,海马IL-1β、TNF-α、PGE₂和IL-10 mRNA和蛋白水平明显升高（P<0.05,P<0.01）。阿魏酸钠和氟西汀均能不同程度地改善CUMS诱导的上述改变。结论：阿魏酸钠能明显改善CUMS所致的大鼠抑郁样行为,其机制可能与降低海马氧化应激水平和改善炎症反应相关。     

法舒地尔治疗慢性心力衰竭临床观察

目的：观察法舒地尔对心力衰竭患者心脏功能及炎症因子的影响。方法：连续入选2009年1月-2012年12月住院的慢性心力衰竭患者86例,随机分为法舒地尔治疗组与对照组,连续治疗14 d,观察治疗前后患者血压、心率、舒张早期左心室充盈峰速度（E）、心房收缩期左心室充盈峰速度（A）、左室射血分数（LVEF）、6 min步行试验（6MWT）、血浆BNP、CRP、IL-6、IL-10、TNF-α水平。结果：与对照组相比,治疗组患者EF改善显著（P<0.05）;6MWT显著增加（P<0.05）,收缩压、舒张压降低（P<0.05）,及心率无明显变化（P>0.05）,血浆BNP、IL-6、TNF-α水平明显降低（P<0.05,P<0.01）。结论：法舒地尔在治疗慢性心力衰竭有一定疗效,可能与其降低血压和干预炎症细胞因子相关。     

初诊2型糖尿病短期胰岛素泵强化治疗对血清炎症因子及胰岛功能的影响

目的：观察短期胰岛素泵强化治疗对初诊2型糖尿病患者（T2DM）血清C反应蛋白（CRP）、肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）水平及胰岛β细胞功能的影响。方法：初诊T2DM患者64例,应用胰岛素泵强化治疗14 d,比较治疗前后血清CRP、TNF-α、IL-6、胰岛素分泌指数（HOMA-IS）、胰岛素抵抗指数（HOMA-IR）的变化,并与38例健康对照组人群进行比较。结果：T2DM患者治疗前血清CRP、TNF-α、IL-6水平较正常对照组明显升高（P<0.01）;强化治疗后较治疗前血清CRP、TNF-α、IL-6水平明显降低（P<0.01）,HOMA-IS明显升高（P<0.01）,而HOMA-IR则明显降低（P<0.01）。结论：初诊T2DM患者存在慢性炎症反应,胰岛素具有抗炎作用,胰岛素强化治疗可改善患者糖代谢,减轻胰岛素抵抗,从而降低炎症因子的表达。     

罗格列酮对脓毒症大鼠肠道黏膜组织中PepT1蛋白表达的干预

目的：探讨罗格列酮对脓毒症大鼠凝血功能、炎性介质及对肠道黏膜组织中PepT1蛋白表达的干预。方法：将45只SD大鼠随机均分为3组：假手术组、模型组和实验组,模型组和实验组采用盲肠结扎穿孔法建立脓毒症大鼠模型,假手术组仅进行盲肠探查。实验组术前给予20 mg·kg^-1罗格列酮灌胃,其余各组大鼠均灌胃等量生理盐水。分别于术后0,24,48 h采用全自动血凝分析仪检测大鼠凝血功能指标水平、酶联免疫吸附试验（ELISA）检测大鼠血清炎性介质水平;蛋白免疫印迹（WB）法检测大鼠空肠黏膜组织中寡肽转运蛋白1（PepT1）蛋白表达。结果：术后24 h、48 h模型组和实验组大鼠PAI-1水平高于假手术组,PT、APTT较假手术组延长（P<0.05）,其中实验组大鼠PT、APTT较模型组缩短、PAI-1水平均低于模型组（P<0.05）。术后24 h、48 h模型组和实验组大鼠血清IL-10水平低于假手术组,TNF-α水平高于假手术组（P<0.05）,且实验组大鼠血清IL-10水平高于模型组,TNF-α水平低于模型组（P<0.05）。假手术组、模型组和实验组大鼠空肠黏膜组织中PepT1蛋白相对表达量分别为0.86±0.29、0.52±0.13、0.79±0.22。与假手术组比,模型组和实验组大鼠空肠黏膜组织中PepT1蛋白相对表达量降低（P<0.05）;与模型组比,实验组大鼠空肠黏膜组织中PepT1蛋白相对表达量升高（P<0.05）。结论：罗格列酮可调控脓毒症大鼠炎性介质水平,改善凝血功能,其干预机制与增加肠道黏膜组织中PepT1蛋白表达、改善肠道功能有关。     

川芎嗪对内毒素诱导的急性肺损伤大鼠肺纤维化和炎症反应的调节作用

目的：探索川芎嗪对内毒素诱导的急性肺损伤大鼠肺纤维化和炎症反应的影响及其机制。方法：大鼠随机分为5组：对照组、LPS模型组、LPS+川芎嗪（50,100,200 mg·kg^-1）组。苏木素伊红（HE）染色观察肺组织病变。Masson染色分析肺纤维化。酶联免疫吸附实验（ELISA）检测白细胞介素（interleukin,IL）-6,IL-1β,肿瘤坏死因子（tTNF-α）和IL-18水平。蛋白印记检测α平滑肌肌动蛋白（α-SMA）,转化生长因子β1（TGF-β1）,Ⅰ型胶原蛋白（collagen type Ⅰ）,Ⅲ型胶原蛋白（collagen type Ⅲ）,PI3K,P-PI3K,AKT,P-AKT,mTOR和P-mTOR的蛋白水平。结果：LPS模型组大鼠肺组织湿/干重之比高于对照组（P<0.01）。与LPS模型组相比,LPS+川芎嗪（100,200 mg·kg^-1）组大鼠肺组织湿/干重之比降低（P<0.01）。川芎嗪处理可改善LPS模型组大鼠肺组织病变及纤维化。LPS模型组大鼠α-SMA,TGF-β1,collagen type Ⅰ和collagen type Ⅲ表达高于对照组（P<0.01）。与LPS模型组相比,LPS+川芎嗪（50,100,200 mg·kg^-1）组大鼠α-SMA、TGF-β1、collagen type Ⅰ和collagen type Ⅲ表达降低（P<0.01）。与对照组相比,LPS模型组大鼠IL-6、IL-1β、IL-18和TNF-α水平升高（P<0.01）。LPS+川芎嗪（50,100,200 mg·kg^-1）组大鼠IL-6、IL-1β、IL-18和TNF-α水平低于LPS模型组（P<0.01）。LPS模型组大鼠P-PI3K/PI3K,P-AKT/AKT和P-mTOR/mTOR比值高于对照组（P<0.01）。与LPS模型组相比,LPS+川芎嗪（50,100,200 mg·kg^-1）组大鼠P-PI3K/PI3K,P-AKT/AKT和P-mTOR/mTOR比值下降（P<0.01）。结论：川芎嗪可通过抑制PI3K/AKT/mTOR信号通路活化减轻内毒素诱导的急性肺损伤大鼠肺纤维化和炎症反应。     

瑞舒伐他汀对慢性阻塞性肺疾病大鼠气道炎症的抑制作用及对TLR4/NF-κB信号通路的影响

目的：分析瑞舒伐他汀对慢性阻塞性肺疾病（COPD）大鼠气道炎症的抑制作用及对TLR4/NF-κB信号通路的影响。方法：利用烟熏及气道灌入脂多糖的方法建立大鼠COPD模型。60只SD大鼠随机分为对照组（n=20）、COPD组（n=20）、瑞舒伐他汀组（n=20）。瑞舒伐他汀组大鼠5.0 mg·kg^-1的瑞舒伐他汀,每日灌胃1次。检测各组大鼠的肺功能指标如肺活量（FVC）、呼气峰值流速（PEF）以及0.1 s呼气量（FEV0.1）及肺组织病理变化。酶联免疫吸附法检测血清白细胞介素（IL）-6、IL-8与肿瘤坏死因子（TNF）-α含量。Western印迹法检测肺组织NF-κB、黏附分子1、黏蛋白5AC、TLR4蛋白表达。荧光定量PCR法检测肺组织NF-κB、黏附分子1、黏蛋白5AC、TLR4 mRNA表达。结果：COPD组各项肺功能指标显著低于对照组（P<0.05）,瑞舒伐他汀组显著高于COPD组（P<0.05）。显微镜下观察,对照组肺泡组织结构正常。COPD组肺泡壁显著变薄,且肺泡出现破裂、融合,肺大疱形成,周围可见炎细胞浸润。瑞舒伐他汀组肺损伤明显轻于COPD组。COPD组IL-6、IL-8与TNF-α的含量显著高于对照组（P<0.05）,而瑞舒伐他汀组显著低于COPD组（P<0.05）。COPD组大鼠肺组织中黏附分子1、黏蛋白5AC、NF-κB及TLR4蛋白及mRNA水平均显著高于对照组（P<0.05）,而瑞舒伐他汀组显著低于对照组（P<0.05）。结论：瑞舒伐他汀可有效降低COPD大鼠气道炎性反应,其机制可能与降低NF-κB及TLR4表达,抑制TLR4/NF-κB信号通路活性,并降低黏液蛋白的高分泌状态,减轻气道炎性介质的释放有关。     

Gastroprotective effect of 2-mercaptoethane sulfonate against acute gastric mucosal damage induced by ethanol

Gastric mucosal damage induced by ethanol is a serious medical problem. Recent evidences suggest that reactive oxygen species and inflammatory mediators play a key role in the destruction of gastric mucosa. The present study was aimed to evaluate the potential beneficial effect of MESNA (2-mercaptoethane sulfonate) against ethanol-induced gastric mucosal damage in mice. The animals were orally pretreated with vehicle or MESNA and then treated with acidified ethanol to induce gastric mucosal damage. One hour after ethanol ingestion mice were euthanized and stomach samples were collected for biochemical analysis. Macroscopic and histopathological evaluation of gastric mucosa showed that pretreatment with MESNA attenuated gastric lesions induced by ethanol. Administration of MESNA significantly increased glutathione content and superoxide dismutase and catalase activity in the gastric tissues. In addition, MESNA markedly reduced ethanol-induced lipid peroxidation, myeloperoxidase activity, tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, and monocyte chemotactic protein-1 levels. These findings suggest that the thiol-containing compound MESNA is able to decrease alcohol-induced oxidative stress and inflammation in the gastric tissue. It seems that MESNA may have a protective effect against ethanol-induced gastric mucosal damage.     

Protective effect of l-citrulline against ethanol-induced gastric ulcer in rats

We examined the protective effect of l-citrulline on ethanol-induced gastric ulcer in rats. Administration of l-citrulline at doses of 300, 600 and 900mg/kg body weight prior to ethanol ingestion protected the stomach from ulceration. The gastric lesions were significantly attenuated by all doses of l-citrulline as compared to the ethanol group. Pre-treatment with l-citrulline prevented the oxidative damage and the decrease of nitric oxide content as well as the increase of the myeloperoxidase activity. Consequently, significant changes observed included the attenuation in the elevation in total nitric oxide synthase activity and inducible nitric oxide synthase activity as well as the decrease in constitutive nitric oxide synthase activity in the gastric mucosa induced by ethanol. Analysis of serum cytokines of ethanol-induced rats showed a moderate decrease in interleukin-10 with considerable increase of interleukin-6 while l-citrulline inhibited the acute alteration of cytokines. These results suggested the gastroprotective effect of l-citrulline.     

Gastric mucosal protection by acetazolamide derivatives: role of carbonic anhydrase and sulfhydryls

Acetazolamide, a carbonic anhydrase inhibitor, prevents acute gastric hemorrhagic lesions induced by ethanol. We used acetazolamide and other carbonic anhydrase inhibitors to correlate their gastroprotective effects with the degree of inhibition of carbonic anhydrase. Since acetazolamide is a thiadiazole, we also investigated structurally related thiadiazoles that contain sulfhydryls to test the hypothesis that the protection against ethanol-induced gastric erosions is related to the presence of sulfhydryls. Dose-response studies with acetazolamide revealed that the protection did not correlate with the inhibition of carbonic anhydrase in the rat gastric mucosa. The carbonic anhydrase inhibitors sulfanilamide and ethoxzolamide, did not offer protection. Bismuthiol I, a thiadiazole with two sulfhydryls, was twice as protective as 2-amino-5-mercapto-1,3,4-thiadiazole with only one sulfhydryl group. We conclude that the protection by acetazolamide against ethanol-induced lesions is not related to the inhibition of carbonic anhydrase in the gastric mucosa. The gastroprotective effect of acetazolamide and its derivatives may be related to their content of sulfhydryls in an oxidized or reduced state.     

Dual effects of zinc sulphate on ethanol-induced gastric injury in rats: possibly mediated by an action on mucosal blood flow

The present study examines the protective effect of zinc sulphate against ethanol-induced gastric mucosal ulcers in rats. Absolute ethanol decreased the gastric mucosal blood flow and produced haemorrhagic lesions in the glandular mucosa. Zinc sulphate preincubation in an ex-vivo stomach chamber preparation prevented the formation of ethanol-induced lesions and attenuated the decrease of blood flow produced by ethanol. Subcutaneous injection of the same doses of the drug at 15 and 30 min before ethanol exposure, markedly reduced the blood flow and also aggravated ethanol-induced gastric injury; however, when injected at 23 and 24 h before ethanol administration, zinc sulphate protected against lesion formation but had no effect on the vascular changes induced by ethanol in the gastric glandular mucosa. These findings show that the antiulcer effect of zinc sulphate occurs only when the drug is given orally, or injected s.c. 23 and 24 h before ethanol challenge. Furthermore, this protective action is probably not entirely mediated by preservation of the gastric mucosal blood flow.     

Gastroprotective effects of bitter principles isolated from Gentian root and Swertia herb on experimentally-induced gastric lesions in rats

Gentianae Radix, the dried root and rhizoma of Gentiana lutea L. (Gentianaceae), has long been used as a remedy for liver and stomach inflammation, eye troubles, etc. In this paper, the gastroprotective effects of the methanol extract of Gentian root (GM) were studied using different gastric lesion models. In pylorus-ligated rats, administration of GM in the duodenum suppressed gastric juice secretion and total acid output in a dose-dependent manner. Oral or duodenum administration of GM showed significant protection against acute gastric ulcer induced by aspirin plus pylorus ligation, water-immersion restraint stress-induced ulcers, and gastric mucosal injury induced by ethanol. Furthermore, four secoiridoid glycosides, amarogentin (A1), gentiopicroside (A2), amaroswerin (A3), and swertiamarin (A4), were obtained from Gentian root or Swertia herb, and their protective effects against stress-induced ulcers and ethanol-induced gastric mucosal injury were evaluated. The doses required for 50% inhibition (ID₅₀) of A1, A3, and A4 on stress-induced ulcers were calculated to be 5.76, 2.58, and 167 mg/kg respectively. The protective effect of A2 at 250 mg/kg was 26.5%. On ethanol-induced gastritis, 5.0 mg/kg of A1 and A3 showed remarkable suppressive effects (33.7 and 45.4%, respectively), and 20 mg/kg of A4 exhibited a suppressive effect (30.8%). The effects of A1, A3, and A4 on ethanol-induced gastric lesions were canceled by 5.0 mg/kg indomethacin pretreatment. These results suggest that the therapeutic effects of Gentian root on gastric lesions are associated with enhanced mucosal defensive factors via the prostaglandin pathway in the cell membrane, and that secoiridoid glycosides contribute to this activity.     

Vanillyl nonanoate protects rat gastric mucosa from ethanol-induced injury through a mechanism involving calcitonin gene-related peptide

Previous studies have demonstrated that capsaicin-sensitive sensory nerves are involved in the protection of gastric mucosa against damage by various stimuli and calcitoin gene-related peptide (CGRP) is a potential mediator in this process. This study was performed to explore the effect of vanillyl nonanoate, a capsaicin analog, on ethanol-induced gastric mucosal injury and the possible underlying mechanisms. A rat model of gastric mucosal injury was induced by oral administration of acidified ethanol and gastric tissues were collected for analysis of gastric ulcer index, cellular apoptosis, the activities of caspase-3, catalase and superoxide dismutase (SOD), levels of CGRP, TNF-α and malondialdehyde (MDA). The results showed that acute administration of ethanol significantly increased gastric ulcer index concomitantly with increased cellular apoptosis, caspase-3 activity, TNF-α and MDA levels as well as decreased activities of catalase and SOD. Pretreatment with 1mg/kg vanillyl nonanoate significantly attenuated ethanol-induced gastric mucosal injury and cellular apoptosis accompanied by increase of CGRP expression, and SOD activity and decrease of caspase-3 activity, TNF-α and MDA levels. The effects of vanillyl nonanoate were inhibited by capsazepine, an antagonist of capsaicin receptor. Our results suggested that vanillyl nonanoate was able to protect the gastric mucosa against ethanol-induced gastric mucosal injury. The underlying mechanism is related to stimulation of CGRP release and subsequent suppression of ethanol-induced inflammatory reaction, cellular apoptosis and oxidative stress.     

Effects of sucralfate on gastric irritant-induced necrosis and apoptosis in cultured guinea pig gastric mucosal cells

We previously reported that several gastric irritants, including ethanol, hydrogen peroxide, and hydrochloric acid, induced both necrosis and apoptosis in cultured gastric mucosal cells. In the present study, we examined the effects of sucralfate, a unique gastroprotective drug, on gastric irritant-induced necrosis and apoptosis produced in vitro. Sucralfate strongly inhibited ethanol-induced necrosis in primary cultures of guinea pig gastric mucosal cells. The preincubation of cells with sucralfate was not necessary for its cytoprotective effect to be observed, thus making its mechanism of action different from that of other gastroprotective drugs. Necrosis of gastric mucosal cells induced by hydrogen peroxide or indomethacin was also suppressed by sucralfate. On the other hand, sucralfate only weakly inhibited ethanol-induced apoptosis. These results suggest that the cytoprotective effect of sucralfate on gastric mucosa in vivo can be explained, at least in part, by its inhibitory effect on gastric irritant-induced necrosis.     

Effects of the synthesized prostaglandin E2-analogue arbaprostil on gastric mucosal lesions in rats

The effects of arbaprostil (CU-83), a newly synthesized prostaglandin (PG) E2 analogue, on gastric lesions were investigated. Experiment 1: The animals were divided into 3 groups: 1. the control group: untreated, 2. 50% ethanol group: rats were given 1 ml of 50% ethanol intragastrically, and 3. arbaprostil + 50% ethanol group: arbaprostil (10 micrograms/kg) was administered p.o. 30 min before 50% ethanol administration. 1 h after ethanol administration, stomachs were isolated, and gastric mucosal lesions were observed. Experiment 2: Rats were divided into 4 groups; 1. the control group; untreated, 2. 6 h stress group; animals were placed in a stress cage and immersed into a water bath (23 degrees C) for 6 h, 3. arbaprostil (10 micrograms/kg) + 6 h stress group, and 4. arbaprostil (100 micrograms/kg) + 6 h stress group; arbaprostil 10 micrograms/kg or 100 micrograms/kg was administered 30 min before 6 h of water immersion stress, respectively. In each experiment, stomachs were isolated and gastric mucosal lesions were observed. Immediately after the observation of lesions, the fundic mucosal layer was separated from the muscle layer, and mucosal PGs levels were measured by high performance liquid chromatography. Four kinds of PGs, i.e., 6-keto-PG F1 alpha, PGF2 alpha, PGE2, and PGD2 were detected in gastric mucosa. Administration of 50% ethanol and water immersion stress induced gastric lesions and decreased all 4 mucosal PGs levels. Arbaprostil, 10 micrograms/kg, reduced ethanol-induced gastric lesions and maintained mucosal PGs levels, concomitantly, however, the same doses of arbaprostil did not show a protective effect against water immersion stress-induced gastric lesions or decreases in PGs levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

The antioxidative and antihistaminic effect of Nigella sativa and its major constituent, thymoquinone on ethanol-induced gastric mucosal damage

The aim of this study was to assess the possible protective effects of Nigella sativa (NS) and its constituent, thymoquinone (TQ) on ethanol-induced gastric mucosal damage in an experimental model. Forty male rats aged four months were divided into four groups (each group containing ten animals); the control group received physiologic saline (10 ml kg⁻¹) and the ethanol group had taken 1 ml (per rat) absolute alcohol by gavage. The third and fourth groups also received NS (500 mg kg⁻¹) and TQ (10 mg kg⁻¹) by gavage 1 h before alcohol administration, respectively. Both drugs (NS and TQ) could protect the gastric mucosa against the injurious effect of absolute alcohol and promote ulcer healing as evidenced from the ulcer index values. Gastric damage was confirmed histomorphometrically by significant increases in the number of mast cells (MC) and gastric erosions in ethanol treated rats. The NS treatment significantly decreased the number of MC and reduced the area of gastric erosions. Likewise, TQ treatment was also able to reduce the number of MC and the gravity of gastric mucosal lesions, but to lesser extent compared to NS. Gastric tissue histamine levels and myeloperoxidase activities were found to be increased in ethanol treated rats, and NS or TQ treatment reversed these increases. Results obtained from this study suggest that both drugs, particularly NS could partly protect gastric mucosa from acute alcohol-induced mucosal injury, and these gastroprotective effects could be due to their antiperoxidative, antioxidant and antihistaminic effects.