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1.
目的:研究双环醇对酒精中毒小鼠肝脏细胞凋亡的保护作用,并从酒精代谢、氧化应激、硝化应激、线粒体损伤、内源性与外源凋亡信号传导通路探讨相关作用的分子机制。方法:ICR小鼠灌胃给予双环醇200,300mg/kg,连续三次。末次给药1h后给予酒精6g/kg,每12h一次,共三次,末次给予酒精10h后处死动物。采用生化法测定血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转氨酶(AST)活性:肝脏线粒体和胞浆乙醇脱氢酶(ADH)、乙醛脱氢酶活性(ALDH)、微粒体CYP2E1活性;肝脏胞浆NAD+/NADH、线粒体谷胱甘肽(GSH)含量、膜电位、肿胀度、呼吸链复合酶Ⅰ和Ⅳ(MRCⅠ、MRCⅣ)活性;肝脏诱导型一氧化氮合酶(iNOS)活性、一氧化氮(NO)含量。应用WesternBlot法检测肝脏环氧合酶.2(COX.2)、iNOS、CYP2E1、Bax、Bcl—XS/L、Fas、Fas-L、细胞色素C表达,TUNEL法检测细胞凋亡,HE染色检测病理形态学变化。结果:双环醇200,300mg/kg对酒精中毒小鼠肝脏损伤和细胞凋亡具有明显保护作用,表现为降低升高的ALT、AST水平,减轻肝细胞髓样变性和小空泡变性等病理学改变,抑制COX-2过表达,减少TUNEL阳性细胞数目。双环醇还可抑制乙醇诱导的ADH、ALDH和CYP2E1活性升高,提高线粒体GSH含量,降低胞浆NAD’/NADH比例,降低肝脏NO含量,抑制iNOS活性和表达,恢复线粒体膜电位,减轻线粒体肿胀度,维持MRC活性,抑制Bax、Fas、Fas-L表达,提高Bcl-XS/L表达,减少线粒体细胞色素C释放。结论:双环醇对酒精中毒小鼠肝脏损伤和细胞凋亡具有明显的保护作用,其作用机制与调节酒精代谢,抑制氧化和硝化应激,减轻线粒体损伤,抑制凋亡相关蛋白表达、增加抗凋亡蛋白表达,从而调控内源性与外源性细胞凋亡信号传导通路相关。  相似文献   

2.
目的:研究天麻素(Gastrodin)对谷氨酸诱导的大鼠肾上腺嗜铬细胞瘤PC12细胞损伤的影响及可能机制。方法:以谷氨酸建立体外培养PC12细胞损伤模型并采用MTT比色法测定细胞存活率;AO/EB双染法经荧光显微镜观察细胞凋亡形态;采用流式细胞术检测细胞内活性氧含量以及Annexin V/PI染色后的细胞凋亡率;Western blot法检测细胞内Caspase-3蛋白表达。结果:天麻素可明显抑制谷氨酸诱导的PC12细胞凋亡,在0.1~10μmol/L剂量呈一定的量效关系;同时,天麻素可明显抑制谷氨酸引起的活性氧(ROS)的累积,降低谷氨酸诱导的活性Caspase-3蛋白的表达,降低PC12细胞的凋亡率,在0.1~10μmol/L剂量呈量效相关性。结论:在一定剂量范围内,天麻素对谷氨酸损伤的PC12细胞具有保护作用,其机制可能与减少ROS的生成,阻止氧化损伤的发生,抑制Caspase-3途径依赖的细胞凋亡相关。  相似文献   

3.
用结扎左冠状动脉前降支法建立大鼠急性心肌缺血再灌注损伤模型 ,用免疫组织化学方法检测 HSP70表达 ,用TUNEL 技术检测心肌细胞凋亡。结果显示 ,在急性心肌缺血再灌注损伤过程中 ,HSP70和细胞凋亡均呈现明显地动态性表达并有着明显的相关性 ;HSP70的代偿性增加可能抑制细胞凋亡的发生 ;细胞凋亡的发生可能是诱发 HSP70表达的一个重要机制。  相似文献   

4.
孙乐科  胡琳凤  柯波 《江西医药》2023,(1):12-15+19
目的 建立坏死性小肠结肠炎(NEC)新生大鼠模型并研究维生素D3干预对肠道保护作用。方法 采用人工代乳品、缺氧和冷应激的方法诱导新生大鼠NEC,干预组提前给予维生素D3干预。HE病理和TUNEL染色检测肠管组织病理变化和细胞凋亡,ELISA实验和免疫组化染色分别检测肠道组织中炎症因子和凋亡蛋白的表达水平。结果 病理结果显示维生素D3干预可明显减少NEC新生大鼠肠道凋亡细胞数量,减轻组织损伤;ELISA和免疫组化染色结果显示维生素D3干预可降低肠道组织炎症因子TNF-α的表达水平,还降低Cleaved-Caspase3、iNOS和COX2表达水平。结论 维生素D3干预可降低NEC大鼠肠道组织炎症因子的表达,抑制细胞凋亡,发挥肠道保护作用。  相似文献   

5.
目的探讨沙棘原花青素对应激性胃溃疡大鼠上皮细胞凋亡与增殖的影响及其可能的机制。方法60只♂W ist-ar大鼠随机分为6组:正常组,对照组,低、中、高剂量组及雷尼替丁阳性对照组。采用束缚-浸水应激的方式造应激性胃溃疡模型,造模前灌胃不同剂量的SBPC或阳性药物。测定溃疡指数、大鼠血浆EGF及NO的水平;大鼠血浆NOS及iNOS的活性;免疫组化的方法测定胃粘膜组织中iNOS、EG-FR及PCNA的表达;采用原位末端标记法检测胃粘膜上皮细胞的凋亡。结果与对照组相比,高剂量组SBPC(150 mg.kg-1)的溃疡指数明显降低(P<0.01);血浆EGF的水平升高(P<0.05),血浆NO的浓度(P<0.01)降低;NOS及iNOS的活力降低(P<0.05);粘膜中的iNOS的表达降低(P<0.01),EGFR的表达增强((P<0.01),PCNA的表达增强(P<0.05),凋亡指数降低(P<0.05)。结论SBPC可能通过调节EGF和NO促进大鼠的细胞增殖抑制细胞凋亡,从而对应激性胃溃疡的发生起保护作用。  相似文献   

6.
目的:观察脑缺血再灌注损伤大鼠海马神经元凋亡及c-fos蛋白的表达。方法:采用大脑中动脉阻断法制备大鼠脑缺血再灌注模型,取海马组织,用免疫组织化学方法检测海马神经元c-fos蛋白表达及TUNEL法观察细胞凋亡情况。结果:脑缺血再灌注损伤大鼠与对照组比较海马区c-fos蛋白阳性细胞表达增强(P〈0.05),凋亡细胞表达增多(P〈0.05)。结论:脑缺血再灌注损伤大鼠海马区c-fos蛋白阳性细胞表达增强,凋亡细胞表达增多。  相似文献   

7.
摘要:目的:基于人趋化因子Fractalkine (CX3CL1)/人趋化因子Fractalkine受体(CX3CR1)轴探讨槲皮素对大鼠血管平滑肌细胞(VSMC)增殖的抑制作用。方法:设VSMC细胞组、西拉普利组(100.0μg·ml-1)、槲皮素低、高剂量组(槲皮素终浓度分别为100.0,200.0μg·ml-1);各组每孔设6个平行样,培养72 h。培养结束后,CCK-8溶液试剂测定细胞增殖水平,结晶紫染色测定单克隆形成数目,流式细胞仪分析细胞凋亡水平,RT-PCR法及Western-Blot法测定细胞CX3CL1、CX3CR1基因和蛋白水平。结果:与VSMC细胞组比较,西拉普利组、槲皮素低、高剂量组吸光度(A)值、存活率、单克隆形成数目、CX3CL1、CX3CR 1mRNA和蛋白表达水平降低,而凋亡率升高(P<0.05)。与西拉普利组比较,槲皮素低剂量组A值、存活率、单克隆形成数目、CX3CL1、CX3CR1 mRNA和蛋白表达水平升高,而凋亡率降低(P<0.05);槲皮素高剂量组A值、存活率、单克隆形成数目、CX3CL1、CX3CR1 mRNA和蛋白表达水平降低,而凋亡率升高(P<0.05);且槲皮素高剂量组A值、存活率水平、单克隆形成数目、CX3CL1、CX3CR1 mRNA和蛋白表达水平低于槲皮素低剂量组,而凋亡率高于槲皮素低剂量组(P<0.05)。结论:在100.0~200.0μg·ml-1的范围内,槲皮素能抑制大鼠血管平滑肌细胞增殖,促进大鼠血管平滑肌细胞凋亡;其机制可能与槲皮素能抑制大鼠血管平滑肌细胞CX3CL1、CX3CR1 mRNA和蛋白表达水平进而抑制CX3CL1/CX3CR1轴的激活有关。  相似文献   

8.
三七总皂甙对大鼠脊髓损伤后iNOS表达及细胞凋亡的影响   总被引:5,自引:0,他引:5  
目的探讨大鼠脊髓损伤后应用三七总皂甙对诱导型一氧化氮合酶(iNOS)表达及细胞凋亡的影响。方法采用Allen’s法将64,只成年SD大鼠造成脊髓中度损伤模型,再随机分为损伤组和三七总皂甙组,分别给予生理盐水及三七总皂甙注射液治疗,损伤后不同时间点(1、3、7、14d)处死大鼠,用HE染色观察损伤脊髓组织病理变化,用免疫组化染色检测iNOS阳性细胞,原位末端标记法(TUNEL法)标记凋亡细胞。结果HE染色镜检发现脊髓组织病理学改变三七总皂甙组明显轻于损伤组;两组均发现iNOS表达及凋亡细胞,且损伤组iNOS表达及神经细胞凋亡指数均高于三七总皂甙组(P<0.05)。结论三七总皂甙注射液能抑制脊髓损伤后iNOS表达及神经细胞凋亡。  相似文献   

9.
詹剑  杨丽  余昌胤  范瑞明 《贵州医药》2009,33(3):206-208
目的通过观察血管紧张素Ⅱ受体拮抗剂(ARB)对肾性高血压大鼠脑缺血再灌注后神经功能、细胞凋亡和NOS的影响,以探讨ARB的脑保护机制。方法Wistar雄性大鼠采用狭窄肾动脉方法建立肾性高血压大鼠模型,随机分为缬沙坦大剂量组(VB组)、缬沙坦小剂量组(VS组)、对照组(C组),分别采用缬沙坦12mg/kg、缬沙坦6mg/kg和生理盐水进行灌胃治疗4周;采用大脑中动脉线栓法造成大脑缺血再灌注模型,缺血时间为2h,再灌注24h,假手术组(N组)作为空白对照。进行神经功能评分后取脑,采用免疫组织化学技术检测脑组织eNOS、iNOS、nNOS的表达,TUNLE法检测脑细胞凋亡情况。结果缬沙坦大剂量组和小剂量组大鼠的神经功能评分显著低于对照组(P〈0.05,P〈0.05),细胞凋亡显著低于对照组(P〈0.05,P〈0.05),eNOS表达水平显著高于对照组(P〈0.05,P〈0.05),nNOS和iNOS表达显著低于对照组(P〈0.05,P〈0.05);缬沙坦大剂量组细胞凋亡显著低于小剂量组(P〈0.05),eNOS表达水平明显高于小剂量组(P〈0.05),nNOS、iNOS表达水平明显低于小剂量组(P〈0.05)。结论ARB能明显改善局灶性脑缺血大鼠的神经功能,减少细胞凋亡,上调脑组织eNOS的表达,抑制nNOS、iNOS表达,提示对脑缺血-再灌注损伤有脑保护作用,上述作用可能具有剂量依赖性。  相似文献   

10.
陈建  施金龙  施炜  毛伟峰  徐水珠 《江苏医药》2005,31(10):765-767
目的探讨诱导型一氧化氮合酶(iNOS)抑制剂氨基胍(AG)对大鼠创伤性脑损伤(TBI)的神经保护作用。方法采用改进的Feeney法大鼠脑损伤模型,对生理盐水(NS)组和AG组SD大鼠于伤后6h分别腹腔注射NS或AG,每隔24h注射1次,连续注射3次。分别于致伤后24h、72h、168h取样,采用iNOS免疫组化技术,研究大鼠TBI后iNOS的表达及其细胞定位,采用凋亡细胞原位缺口末端标记法(TUNEL),观察大鼠TBI后不同时点的神经细胞凋亡情况。结果大鼠TBI后24h,大脑损伤区周围皮质和伤侧海马iNOS阳性表达,TUNEL阳性细胞均明显增多,伤后72h表达最明显,伤后168h仍有表达;注射AG后,大脑损伤区周围皮质和伤侧海马的iNOS阳性细胞和TUNEL阳性细胞均明显减少(P〈0.01)。结论TBI后损伤区周围皮质和伤侧海马可出现iNOS阳性细胞高表达和神经细胞凋亡,且呈相关性变化,推测iNOS的过度表达可能参与了TBI后继发性神经细胞凋亡,使用AG能明显减少iNOS阳性细胞的表达和神经细胞的凋亡。  相似文献   

11.
目的:研究不同剂量奥美拉唑对大鼠中毒性急性胃黏膜损伤的保护作用,探讨其保护机制。方法:40只SD大鼠随机分成空白对照组,急性中毒对照组,小剂量奥美拉唑治疗组(10mg/kg)和大剂量奥美拉唑治疗组(50mg/kg)。造模后计算溃疡指数,测定血浆内皮素(ET)、血清肿瘤坏死因子α(TNF-α)及胆碱酯酶活力,镜下观察胃黏膜病理改变。结果:成功建立急性胃黏膜损伤动物模型;在此基础上采用奥美拉唑治疗可改善中毒大鼠血液相关检测指标,显著改善胃黏膜溃疡指数(UI)及组织病理情况;且大剂量奥美拉唑组的疗效优于小剂量组(P〈0.05)。结论:奥美拉唑治疗能够改善大鼠口服有机磷农药中毒所致的急性胃黏膜损伤,大剂量奥美拉唑治疗的效果更明显;ET、TNF-α不但可作为急性中毒性胃黏膜损伤时早期血液检测指标,而且可作为治疗急性中毒性胃黏膜损伤效果的监测指标。  相似文献   

12.
The pharmacology, pharmacokinetics, clinical efficacy, contraindications and precautions, adverse effects, dosage, and cost of misoprostol are reviewed. Misoprostol is a synthetic analogue of natural prostaglandin E1. It produces a dose-related inhibition of gastric acid and pepsin secretion and enhances mucosal resistance to injury. Misoprostol is extensively absorbed from the stomach and undergoes rapid de-esterification to its biologically active metabolite, misoprostol acid. The average absorption after an oral dose is 88%; peak plasma concentrations of misoprostol acid are achieved in less than 30 minutes. Clinical trials have demonstrated ulcer healing rates of approximately 60-80% in patients with duodenal ulcers who received misoprostol 800 micrograms daily for four weeks. Misoprostol was generally no more efficacious than conventional therapy with the H2-receptor antagonists cimetidine and ranitidine. The healing rate observed for gastric ulcers was less than that observed for duodenal ulcers. In trials involving healthy volunteers and patients with arthritis receiving aspirin, naproxen, tolmetin, ibuprofen, or piroxicam, misoprostol was consistently superior to placebo, cimetidine, and sucralfate in the prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. The majority of these studies have been of short duration; however, long-term studies (up to three months) have corroborated superiority over placebo. Misoprostol is an abortifacient and is contraindicated in pregnant women and women of childbearing potential not using effective contraception. The most common adverse effect of misoprostol therapy is diarrhea, which is often mild and self-limiting and can be minimized by administration of misoprostol after meals and at bedtime. The cost (based on retail price) of four weeks of therapy with misoprostol is comparable to that of other antiulcer agents. Misoprostol has been shown to be an effective agent for the prevention of NSAID-induced gastric ulcers. However, there is no evidence that it offers any clinical advantage over H2-receptor antagonists for the treatment of gastric or duodenal ulcer disease.  相似文献   

13.
The evaluation of mucosal damage in experimental models of gastric injury is commonly based on macroscopic detection of gross lesions and/or histological examination of tissue samples and is limited by the subjectivity of the examiner and by the paucity of nonrepresentative samples. This study proposes a novel method for the histomorphometric analysis of gastric damage, based on the examination of seriate parallel strips taken from whole rat stomachs. Strips were cut perpendicular to the lesser curvature, placed on a glass slide, with the side of each strip distal to the pylorus upward, and processed for routine histology. Sections were then observed by light microscopy: the length of damaged mucosa divided by the total length of mucosa, measured on a micrometric scale and expressed in percentage values, was indicated as the lesion index. Furthermore, to evaluate the severity of the damage, three types of lesions were discriminated depending on their depth: type I, lysis of luminal cells; type II, damage involving the cells lying on both surface mucosa and gastric pits; and type III, damage involving the lower part of the lamina propria with injury of glands associated with detachment of whole mucosal layers. Three models of acute gastric damage (ethanol, hemorrhagic shock, and indomethacin) were examined and treatment was also carried out with the antiulcer drugs omeprazole, ranitidine, and misoprostol, to show the advantages of this histomorphometric approach. The results indicate that this method allows an accurate quantitative analysis of gastric damage, and the effects of different antiulcer drugs can be better discriminated.  相似文献   

14.
J P Monk  S P Clissold 《Drugs》1987,33(1):1-30
Misoprostol is an analogue of prostaglandin E1 and is the first synthetic prostaglandin analogue to be made available for the treatment of peptic ulcer disease. It inhibits gastric acid secretion in man, and there is also some evidence that it limits the extent of gastrointestinal damage induced by ulcerogenic agents in animals and healthy volunteers at doses lower than those required to inhibit acid secretion. This 'cytoprotective' activity has been explained by several mechanisms, but its contribution to the clinical efficacy of misoprostol in healing established ulcers is doubtful since the drug does not appear to be effective in healing peptic ulcers at non-antisecretory dosages. In clinical trials, ulcer healing has been reported in 60 to 85% of patients with duodenal ulcers and 32 to 54% with gastric ulcers receiving misoprostol 200 micrograms 4 times daily for 4 weeks--the recommended dosage. In comparative studies, the percentage of patients with healed ulcers after misoprostol (800 micrograms daily) was not significantly different from that with cimetidine (1200 mg daily), although there was greater pain relief with cimetidine. No study has yet been published concerning the use of misoprostol as maintenance therapy for the prevention of ulcer recurrence, and no long term tolerability data are available. However, in acute ulcer healing studies (2 to 12 weeks in duration) misoprostol has been well tolerated. Diarrhoea was the most commonly reported symptom, and this was only rarely of sufficient severity to interfere with treatment. No evidence of histopathological changes in the gastric mucosa induced by misoprostol have been reported in man. Evidence of uterine stimulant effects in women receiving misoprostol during the first trimester of pregnancy has resulted in the drug being contraindicated during pregnancy. Thus, misoprostol is a new type of antiulcer drug, providing an alternative approach to the therapy of peptic ulcer disease. It has been shown to be effective and well tolerated in the healing of both gastric and duodenal ulcers. Future studies need to identify the specific types of patients likely to obtain most benefit from treatment, in order to define more clearly the place of misoprostol in the treatment of these indications, as well as addressing the possibility of ulcer prevention with lower doses of misoprostol.  相似文献   

15.
INTRODUCTION: The harmful effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the gastric mucosa and the prophylactic effects of misoprostol are both dose-dependent. AIM: To investigate whether a low-dose of misoprostol is sufficient to prevent gastric mucosal injury caused by low-dose aspirin. METHODS: We conducted a double-blind placebo controlled parallel group endoscopic study in 32 evaluable volunteers. The main outcome measure was erosive injury (ulcers and superficial erosions) in the gastric mucosa over 28 days. RESULTS: Most subjects developed erosions on aspirin 300 mg daily. This was significantly reduced by misoprostol 100 microg daily. (Odds ratio 0.18, 95% CI: 0.07-0.48). There were no drug-related or gastrointestinal adverse events in subjects receiving misoprostol. CONCLUSION: Misoprostol 100 microg daily can prevent low-dose aspirin induced gastric mucosal injury without causing identifiable adverse effects.  相似文献   

16.
17.
The effects of morphine on gastric secretion, barrier mucus and mucosal lesions were studied in pylorus-ligated rats treated with the ulcerogenic agents, indomethacin, aspirin or taurocholic acid. All three ulcerogenic agents induced significant mucosal lesions. Morphine decreased gastric acid secretion and suppressed the aspirin- and taurocholic acid-induced, but not the indomethacin-induced mucosal lesions. These results suggest that the ulcerogenic mechanisms of indomethacin and the other agents are not identical. Moreover the antiulcer effect of morphine appears to be mediated by an increased barrier mucus level: the amount of Alcian blue bound to the mucosa, an indirect estimate of the adherent mucus layer, was increased by morphine and correlated with its protective effect. All morphine effects were reversed by naloxone.  相似文献   

18.
中药胃康胶丸对急性胃损伤大鼠胃黏膜血流的影响   总被引:1,自引:0,他引:1  
刘生杰  董圣惠  王瑾  窦燕  梁浩 《中国新药杂志》2006,15(1):33-35,i0001
目的:观察中药胃康胶丸对大鼠急性胃损伤后黏膜血流的影响。方法:采用寒冷应激法诱发急性胃损伤大鼠模型,给药7d后,用激光多普勒血流仪测定胃黏膜血流。结果:胃康胶丸组大鼠胃黏膜血流明显高于模型组,胃组织损伤评分均明显低于模型组。与其他给药(L-谷氨酰胺、枸橼酸铋钾、金银花)组比较,胃康胶丸组的作用更明显(P〈0.01)。结论:胃康胶丸可以增加胃黏膜血流量,促进修复。  相似文献   

19.
BACKGROUND: Various animal models of non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulceration exist. These models have limitations, which make them less relevant to the human situation. AIM: : To develop a more simple and more relevant model of NSAID-induced gastric ulceration and adaptation. METHODS: Gastric ulceration was evaluated following the orogastric administration of naproxen (80 mg/kg b.d.) to hamsters. The effects of misoprostol and famotidine on gastric acid secretion and ulceration were also determined. Gastric adaptation was evaluated by proliferating cell nuclear antigen (PCNA) immunohistochemistry, in hamsters given naproxen for 3 weeks. Antral resistance to acute injury by NSAIDs and ethanol was also determined in these animals. RESULTS: Naproxen caused primarily gastric antral ulceration, which decreased from day 3 to day 21. This gastric adaptation was accompanied by an increase in PCNA positive cells, particularly on days 7 and 14. The adapted gastric antral mucosa was resistant to acute damage by various agents. Misoprostol (1 or 100 microg/kg) prevented antral ulceration, without affecting gastric acid secretion. Despite decreasing acid output by> 90%, famotidine (30 mg/kg) failed to prevent ulceration. CONCLUSION: The administration of naproxen (80 mg/kg b.d.) to hamsters is a simple, reliable and relevant method for evaluating NSAID-induced gastric antral ulceration and adaptation.  相似文献   

20.
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.  相似文献   

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