芸香苷对实验性急性胰腺炎的保护作用与抗氧化的关系

目的 :探讨芸香苷 (Rutoside ,Ru )对大鼠实验性急性胰腺炎 (AP)的保护作用与抗氧化作用的关系。方法 :脱氧胆酸钠逆行胆胰管注射诱发大鼠AP模型。观察造模后不同时间血清淀粉酶活性及胰腺组织病理组织学改变 ,检测血清一氧化氮 (NO)水平以及造模后 2 4h胰腺组织中超氧化物歧化酶(SOD)活性和丙二醛 (MDA)含量。结果 :Ru(30 ,6 0 ,12 0mg·kg-1,sc) 3个剂量可不同程度地降低模型大鼠血清淀粉酶活性 ,改善胰腺组织病理组织学损伤 ,恢复升高的血清NO水平 ,提高SOD活性和减少MDA生成。结论 :Ru对实验性急性胰腺炎具有一定的保护作用 ,其作用机制可能与改善机体内源性抗氧化系统、提高血清NO水平和清除氧自由基对胰腺组织的损伤有关。     

芸香苷对小鼠脑缺血损伤保护作用的实验研究

目的　研究芸香苷对脑缺血损伤的保护作用。方法　小鼠脑缺血模型采用双侧颈总动脉结扎法 ;神经细胞凋亡用TUNEL法检测 ;组织学检查用来测定神经细胞形态学变化 ;丙二醛 (MDA)和一氧化氮 (NO)含量分别用TBA法和Green法测定。结果　 5 0、10 0mg·kg-1的Ru则可显著提高脑缺血小鼠的存活率 ,改善神经元和胶质细胞的形态学变化 ;也可显著抑制缺血脑组织中NO及MDA含量的增高及减少缺血脑组织神经元的凋亡数目。结论　Ru对小鼠脑缺血损伤具有保护作用 ,作用机制可能与其抗自由基、抗凋亡及减少NO生成有关。     

药物对乙醇所致胃粘膜损伤的保护作用

随着酒精 (乙醇 )消费人口的增多 ,乙醇对人体的损害作用日益引起人们的重视。大量乙醇摄入后可引起机体多系统损害 ,由于乙醇的局部刺激作用 ,消化道粘膜损伤较为常见。胃是乙醇较早接触的重要脏器 ,乙醇对胃粘膜的损伤机制和药物对胃粘膜的保护机制及作用 ,近年来已成为国内外学者研究的重要课题之一。１对胃粘膜的损伤机制及作用众所周知 ,正常胃粘膜的完整性是由攻击因子与防御因子的动态平衡来维持的 ,一旦这种平衡被破坏将会导致胃粘膜损伤。乙醇作为一种攻击因子 ,可使白细胞浸润于胃粘膜 ,并释放超氧化物、次氯酸等引起组织损伤［１…     

药物对乙醇所致胃粘膜损伤的保护作用

随着酒精(乙醇)消费人口的增多,乙醇对人体的损害作用日益引起人们的重视。大量乙醇摄入后可引起机体多系统损害,由于乙醇的局部刺激作用,消化道粘膜损伤较为常见。胃是乙醇较早接触的重要脏器,乙醇对胃粘膜的损伤机制和药物对胃粘膜的保护机制及作用,近年来已成为国内外学者研究的重要课题之一。     

思密达对大鼠酒精性胃粘膜损害的保护作用

采用酒精灌胃和胃外在体的大鼠动物模型，观察思密达对酒精性胃粘膜损害的保护作用。结果为思密达组胃粘膜损伤明显小于对照组；肥大细胞脱颗粒也少于对照组。同时应用激光多普勒流量仪检测胃粘膜血流，显示思密达组鼠胃粘膜基础血流增加，并减轻酒精引起的胃粘膜血流减少。     

五种不同基源石斛对小鼠胃粘膜损伤的保护作用及机制研究

目的:研究叠鞘、金钗、铁皮、马鞭和鼓槌石斛对小鼠乙醇性胃粘膜损伤的保护作用及其与氧自由基(OFR)、一氧化氮(NO)和前列腺素(PG)的关系.方法:制备小鼠乙醇性胃粘膜损伤模型,测定胃粘膜损伤指数;测定胃组织内SOD、MDA、NO和PGE2含量.结果:石斛可剂量依赖性地抑制无水乙醇诱发的小鼠胃粘膜损伤,使小鼠胃粘膜损伤过程中胃组织中升高的MDA含量降低,使降低的SOD活性和NO水平回升,对胃组织中PGE2含量无明显影响.结论:石斛对小鼠乙醇性胃粘膜损伤具有保护作用,其作用机制与石斛抗氧化作用有关,叠鞘石斛可能与促进NO水平恢复正常也有关系.     

牛磺酸对乙醇性胃粘膜损伤的保护机制初探

目的为了探讨牛磺酸抗乙醇性胃粘膜损伤的作用机制。方法采用大鼠实验性乙醇胃粘膜损伤模型，测定胃粘膜局部一氧化氮合成酶（ＮＯＳ）、内皮素（ＥＴ）和部分胃肠激素含量。结果牛磺酸可明显减轻胃粘膜损伤，抑制ＥＴ释放，增加ＮＯＳ活性及生长抑素（ＳＳ）和血管活性肠肽（ＶＩＰ）的含量。结论牛磺酸可明显减轻实验性乙醇胃粘膜损伤，其可能机制为调节胃粘膜局部ＥＴ、ＮＯＳ、ＳＳ、ＶＩＰ的活性和含量。     

银杏叶提取物对胃粘膜保护作用的机制探讨

银杏叶提取物(GbE)已被广泛用于治疗心脑血管疾病,目前国内有文献提及GbE可显著改善胃、十二指肠溃疡,笔者前期实验工作也证实了GbE具有胃粘膜保护工作,本研究旨在讨论NO在GbE胃粘膜保护机制中的作用。     

芸香苷对急性胰腺炎大鼠血浆TXB_2/6-keto-PGF1α值及胰腺组织NO的影响

目的:研究芸香苷(Ru)对大鼠急性胰腺炎模型(AP)血浆血栓素B(2TXB2)与6-酮基-前列腺素F1α(6-keto-PGF1α)及胰腺组织一氧化氮(NO)的影响。方法:SD大鼠48只,随机分为假手术、模型、丹参及Ru高、中、低剂量组。以牛磺胆酸钠溶液复制大鼠急性胰腺炎模型,测定各组大鼠血浆TXB2/6-keto-PGF1α值、酶学及胰腺组织NO,并做病理检查。结果:Ru能够有效降低AP模型大鼠血浆TXB2/6-keto-PGF1α值,降低胰腺组织的NO含量,减轻胰腺组织水肿、坏死炎症及空泡形成,明显改善胰腺的病理组织学变化。结论:Ru对胰腺组织有一定的保护作用。     

芸香甙对应激性胃粘膜损伤保护作用的机制研究

目的初步研究芸香甙（Ｒｕ）对应激性胃粘膜损伤保护作用的机制。方法采用大鼠冷冻－束缚应激模型，评价胃粘膜损伤指数的变化。ＭＤＡ和ＧＳＨ含量测定分别应用ＴＢＡ和ＤＴＮＢ法，胃粘膜局部血流量（ＧＭＢＦ）测定应用氢气清除法。结果给予Ｒｕ抗溃疡剂量（５，２０ｍｇｋｇ－１，ｉｇ）ｂｉｄ，连续５ｄ，使血清和胃粘膜中因应激而升高的ＭＤＡ含量明显降低，并可升高应激后降低的胃粘膜ＧＳＨ含量。高Ｃａ２＋／低Ｃａ２＋分别可拮抗／增强Ｒｕ的胃粘膜保护作用。Ｒｕ尚可提高应激后降低的ＧＭＢＦ。Ｒｕ的构效关系研究显示，３个剂量（８．２，１６．４，３２．８μｍｏｌｋｇ－１）的Ｒｕ和槲皮素（ｑｕｅｒｃｅｔｉｎ，Ｑｕｅ）均可减轻应激所致的胃粘膜损伤，但Ｒｕ和Ｑｕｅ相同剂量组之间的胃粘膜损伤指数差异无显著性。结论Ｒｕ对应激性胃粘膜损伤保护作用的机制可能与其抗氧化作用、Ｃａ２＋拮抗和改善ＧＭＢＦ有关。Ｒｕ结构中的甙元部分在保护胃粘膜中起主要作用。     

质子泵抑制剂的胃黏膜保护作用与环氧化酶-2表达

目的　探讨质子泵抑制剂 (PPIs)的胃黏膜保护作用与环氧化酶 2 (COX 2 )表达的关系。方法　♂SD大鼠ig给予雷巴拉唑、奥美拉唑或兰索拉唑 5 0mg·kg-1·d-1,对照组ig给予质量分数为 0 5 %羧基纤维素 5ml·kg-1·d-1,连续 2wk。Westernblot和免疫组化检测胃黏膜COX 2表达。酶免疫方法测定胃黏膜中前列腺素E2 (PGE2 )水平 ,评价兰索拉唑和特异性COX 2抑制剂NS 3 98对乙醇所致大鼠胃黏膜损伤的影响。结果　 3种PPI均增加大鼠胃黏膜COX 2的表达。兰索拉唑呈剂量依赖性地增加胃黏膜中PGE2 含量 ,有效地减轻乙醇对胃黏膜的损伤作用。NS 3 98有效地阻断了兰索拉唑诱导的PGE2 合成及胃黏膜保护作用。结论　PPIs通过诱导胃黏膜COX 2表达 ,增加PGE2 合成而发挥胃黏膜保护作用     

芸香甙对脑缺血再灌损伤的保护作用

目的研究芸香甙（Ｒｕ）对脑缺血再灌损伤的保护作用。方法小鼠脑缺血再灌模型通过结扎双侧颈总动脉并尾部放血０．３ｍｌ，再灌后，记录异常神经症状和断头后张口喘气时间，测定脑组织中乳酸脱氢酶（ＬＤＨ）含量；利用４血管模型，大鼠前脑缺血３０ｍｉｎ后再灌注４０ｍｉｎ。取脑组织测定ＬＤＨ、过氧化物歧化酶（ＳＯＤ）、丙二醛（ＭＤＡ）、一氧化氮（ＮＯ）及脑水肿。结果Ｒｕ（５０，１００ｍｇ·ｋｇ－１，ｉｖ），显著改善小鼠脑缺血再灌损伤后的异常神经症状和抑制断头后张口喘气时间的缩短及脑组织中ＬＤＨ的减少。Ｒｕ显著抑制大鼠脑缺血再灌损伤所致的脑水肿形成和脑组织中ＬＤＨ、ＳＯＤ、ＭＤＡ及ＮＯ的变化。结论Ｒｕ对脑缺血再灌损伤有显著的保护作用，其机制与抗自由基和ＮＯ有关。     

Opposite effects of endogenous nitric oxide and prostaglandin F2 alpha in the rat mesenteric bed

1. The relationship between the effects of endogenous nitric oxide (NO) and prostanoids on the noradrenaline (NA)-induced contractions and the mechanisms involved were investigated in the rat perfused mesenteric bed, using NG-nitro-L-arginine methyl ester (l-NAME), a NO synthase inhibitor and sodium nitroprusside (SNP), a NO donor. 2. The constrictor responses to NA were reduced to 50% by the cyclooxygenase inhibitor 10 microm indomethacin as well as by 1 microM SNP. When indomethacin and SNP were perfused simultaneously the contractions were further reduced. 3. The NA-induced contractions were increased by the addition of 400 microM L-NAME and the addition of either indomethacin or SNP abolished such increases. The simultaneous perfusion of both agents further reduced the contractions. 4. Removal of the endothelium increased NA-induced contractions to a similar extent as L-NAME and this increase was abolished by indomethacin as well as by SNP. 5. The perfusion of 10 microM NA augmented the release of prostaglandin (PG) F2 alpha by the mesenteric bed without modifications in any other prostanoid. In the presence of L-NAME, this effect was further increased. However, SNP abolished the NA-induced stimulation of PGF2 alpha release. 6. In de-endothelialized preparations NA also stimulated PGF2 alpha production as observed in intact preparations. This effect was more marked in the presence of L-NAME; in contrast, SNP abolished the stimulation. 7. In conclusion, the present results suggest an opposite action between NO and PGF2 alpha on the NA-induced contractions in the rat mesenteric bed.     

Oxidative stress,nitric oxide and prostaglandin E2 levels in the gastrointestinal tract of aging rats

Objectives To evaluate the presence of oxidative stress and alterations in the levels of two cytoprotective agents, prostaglandin E₂ and nitric oxide, in the gastrointestinal tract of aging rats. Methods The production of superoxide anion, lipid peroxides, levels of superoxide dismutase and catalase, and production of prostaglandin E₂ and nitric oxide in the stomach and duodenum of rats were determined at 1.5, 3, 12, 18 and 24 months of age. Key findings Oxidative stress was present in the stomach of the old rats (24 months), whereas prostaglandin E₂ and nitric oxide production remained stable at 18 and 24 months. In the duodenum, no oxidative stress was observed at 24 months, but at 18 months, an increase in superoxide anion levels was detected. Prostaglandin E₂ remained constant in the aged rats but nitric oxide decreased significantly at 24 months. Conclusions The absence of macroscopic gastric injury throughout the gastrointestinal tract indicates that the oxidative stress in the stomach and the significant decrease of nitric oxide in the duodenum in the old rats are not sufficient to disrupt the mucosal defence network. The results support the notion that the disruption of the mucosal network is essentially regulated by the cytoprotective agents prostaglandin E₂ and nitric oxide, and that injury appears only when both substances are concurrently reduced.     

Role of nitric oxide produced by constitutive and inducible nitric oxide synthases in the mouse gastric fundus

In the present study, the role of nitric oxide (NO) produced by constitutive and inducible nitric oxide synthases (cNOS and iNOS, resepctively) on the contraction and relaxation of fundus in normal and lipopolysaccharide (LPS)-treated mice was examined. A whole fundic ring isolated from mice pretreated with reserpine was mounted in an organ bath containing Krebs' solution with 0.001 mmol/L atropine. Rings were contracted initially by 5-hydroxytryptamine (5-HT; 0.03 mmol/L) before relaxation was induced using ATP (0.03 mmol/L), ADP (0.03 mmol/L), pentoxifylline (0.002 mmol/L), electrical field stimulation (EFS; 50 V, 1 msec, 50 Hz, 3 min) and L-arginine (0.05 mmol/L). All drugs and EFS induced significant relaxation of isolated rings. The relaxations induced were significantly inhibited by N(G)-nitro-L-arginine methyl ester (L-NAME; 1.0 mmol/L). However, the iNOS inhibitors L-N(6)-(1-iminoethyl) lysine hydrochloride (L-NIL; 1.0 mmol/L) and amino guanidine (AMG; 1.0 mmol/L) had no significant effect on tissue relaxation. Then, the relaxant effects of 0.03 mmol/L ATP were tested on precontracted isolated fundic rings taken from 10 mg/kg LPS-treated animals. The non-selective NOS inhibitor L-NAME (10 mg/kg), the iNOS inhibitors L-NIL (3 mg/kg) and AMG (20 mg/kg) and betamethasone (0.1 mg/kg) were used to examine the role of NO produced by iNOS in the relaxation responses. It was found that the level of contraction induced by 0.03 mmol/L 5-HT in rings isolated from LPS-treated animals was significantly (P < 0.5) less than that in rings from untreated mice. However, precontracted tissues from LPS-treated mice were significantly relaxed by ATP and the relaxation response to ATP was significantly inhibited by L-NIL, ANG and betamethasone, but not by L-NAME. We suggest that, in LPS-treated mice, the production of NO from iNOS produces a reduction in the contractile response, as well as a decrease in NO formation by cNOS, resulting in changes to smooth muscle cell function.     

Central ghrelin gastroprotection involves nitric oxide/prostaglandin cross-talk

BACKGROUND AND PURPOSE: Ghrelin, a gut-brain peptide, is considered a gastroprotective factor in gastric mucosa. We investigated the role of prostaglandins (PG) and the possible interplay between PGs and nitric oxide (NO) in ghrelin gastroprotection against ethanol (EtOH)-induced gastric lesions. EXPERIMENTAL APPROACH: We examined the effects of (1) central ghrelin (4 mug per rat) injection on PGE(2) accumulation in normal or EtOH-lesioned gastric mucosa, (2) pretreatment with indomethacin (10 mg kg(-1), p.o.), a non-selective cyclooxygenase (COX) inhibitor, and with a selective COX-1, SC560 (5 mg kg(-1), p.o.) or COX-2 inhibitor, celecoxib (3.5 mg kg(-1), p.o.) on ghrelin gastroprotection against 50% EtOH (1 mL per rat)-induced gastric lesions, (3) the NO synthase inhibitor, L-NAME (70 mg kg(-1), s.c), on gastric PGE(2) content in ghrelin-treated rats and (4) central ghrelin on the expression of constitutive and inducible NOS and COX mRNA and on the localization of the immunoreactivity for COX-2 in the gastric mucosa exposed to EtOH. KEY RESULTS: Ghrelin increased PGE(2) in normal mucosa, whereas, it reversed the EtOH-induced PGE(2) surge. Ghrelin had no effect on mucosal COX-1 expression but reduced the EtOH-induced increase in COX-2 expression and immunoreactivity. Indomethacin and SC560, but not celecoxib, removed ghrelin gastroprotection. L-NAME prevented the PGE(2) surge induced by ghrelin and, like indomethacin, reduced EtOH-induced PGE(2) increase. Ghrelin enhanced eNOS expression and reduced iNOS mRNA. CONCLUSIONS AND IMPLICATIONS: This study shows that COX-1-derived PGs are mainly involved in ghrelin gastroprotection and that the constitutive-derived NO together with PGE(2) are involved in ghrelin gastroprotective activity.     

Prostaglandins, capsaicin-sensitive sensory nerves and neutrophil infiltration, but not nitric oxide, contribute to cold restraint stress-induced gastric adaptation in rats

The aim of the present study was to determine the role of prostaglandins (PG), nitric oxide (NO) and capsaicin-sensitive sensory nerves in neutrophil infiltration in gastric adaptation to cold restraint stress in rats. Wistar rats were exposed to single or repeated cold restraint stress for 3.5 h every other day for up to 4 days. Prior to repeated stress, rats were pretreated with NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg, s.c.), indomethacin (10 mg/kg, s.c.) or capsaicin (125 mg/kg, s.c.). The extent of gastric mucosal lesions was evaluated histologically and myeloproxidase (MPO) activity, PGE2, NO and calcitonin gene-related peptide (CGRP) levels were measured in gastric tissue. Cold restraint stress produced haemorrhagic lesions and reduced PGE2 and CGRP levels in the stomach, with an increase in MPO activity and NO levels. Repeated stress insults reduced stress-induced gastric damage, NO production and MPO activity, with an increase in PGE2 and CGRP levels compared with rats exposed to single cold restraint stress. Adaptation to cold restraint stress was prevented by indomethacin and capsaicin pretreatment, but not by L-NAME. We conclude that the stomach has the ability to adapt to repeated exposure to cold restraint stress and that the adaptation, via inhibition of neutrophil infiltration, is mediated, at least in part, by endogenous PG and CGRP.