环氧合酶-2抑制剂对大鼠胃黏膜损伤愈合的影响

目的　环氧合酶 (COX)是合成前列腺素 (PGs)的关键酶 ,传统的非甾体抗炎药 (NSAIDs)抑制COX 1和COX 2活性 ,引起严重的胃肠道不良反应。特异性COX 2抑制剂有望成为不引起胃损伤的新型NSAIDs。本研究探讨特异性和非特异性COX 2抑制剂对盐酸诱导大鼠胃黏膜损伤愈合的影响。方法　雄性SD大鼠胃内给予 0 .6mol/LHCl1ml,Westernblot和免疫组化法分析胃黏膜COX 1和COX 2表达。盐酸灌胃后 10min ,实验组胃内给予NS 3980 .4、4、4 0mg/kg和吲哚美辛 4 0mg/kg ,对照组胃内给予 1%阿拉伯树胶 (AG) 5ml/kg。盐酸灌胃前和灌胃后 1、3、6、12、2 4及 4 8h分别处死大鼠 ,剖腹取胃 ,观察各组动物损伤指数 (LI)及光镜下的胃黏膜病理学改变。结果　盐酸灌胃后COX 2在表层上皮细胞和颈黏液细胞表达显著增加 ,NS 398和吲哚美辛均延迟胃黏膜损伤的愈合。盐酸灌胃后 12h ,NS 398组 (4和 4 0mg/kg)及吲哚美辛组的LI分别为 (1.4 2± 0 .2 3) % ,(1.4 2± 0 .2 9) %和 (1.6 2± 0 .4 4 ) % ,明显高于对照组的 (0 .5 8± 0 .2 4 ) % (P <0 .0 5 )。结论　特异性和非特异性COX 2抑制剂延迟大鼠胃损伤后的愈合 ,提示COX 2表达在胃黏膜再生过程中起重要作用     

特异性环氧合酶-2抑制剂西乐葆胃黏膜安全性实验研究

目的　比较特异性环氧合酶 2 (COX 2 )抑制剂西乐葆与传统非甾体抗炎药 (NSAIDs)对胃黏膜的损害。方法　分别以西乐葆、吲哚美辛复制大鼠NSAIDs性胃黏膜损伤模型 (n =8) ;以无水乙醇复制胃黏膜急性损伤模型 ,再以西乐葆灌胃 (n =8)。观察各组胃黏膜 6 酮 前列腺素F1α(6 keto PGF1α)、血栓素B2 (TXB2 )水平、损伤指数 (LI)及光镜、扫描电镜下的变化。结果　吲哚美辛组胃黏膜损害明显 (LI :13.38± 2 .0 6 ) ,6 keto PGF1α、TXB2 明显下降 (P <0 .0 1) ,抑制率分别为 81.6 %,81.8%,LI与 6 keto PGF1α、TXB2 水平呈负相关。西乐葆组 6 keto PGF1α、TXB2 无明显抑制 (P >0 .0 5 ) ,对健康胃黏膜无损害 (LI :0 ) ,但可加重乙醇诱导的胃损伤 (LI :37.19± 3.34比 19.90± 2 .2 8,P <0 .0 1)。结论　COX 1活性抑制是NSAIDs胃病的主要机制 ;特异性COX 2抑制剂西乐葆不造成健康鼠胃黏膜损伤 ,有较高的胃肠道安全性 ,但可加重原有胃损伤。     

胃运动功能对乙醇所致大鼠胃黏膜损伤的影响

目的研究普瑞博斯对乙醇所致胃黏膜损伤的影响,以阐明胃运动功能对胃黏膜的保护作用。方法实验包括两部分,实验1：雄性Wistar大鼠24只,随机分为对照组、普瑞博斯小剂量组和大剂量组,分别给予生理盐水、普瑞博斯0．5mg/kg和普瑞博斯1mg／kg灌胃,然后各组均给予无水乙醇灌胃,检测胃黏膜损伤的面积和深度;实验2：大鼠分组同上,实验前所有大鼠均行幽门结扎术,术后给药及胃黏膜损伤的检测方法刚上。结果于末结扎幽门的大鼠中,大剂量普瑞博斯可显著减少无水乙醇所致的胃黏膜损伤深度和面积,小剂量普瑞博斯也可减少胃黏膜损伤的深度。结扎幽门后,普瑞博斯对无水乙醇所致胃黏膜损伤的保护作用消失。结论普瑞博斯对无水乙醇所致的胃黏膜损伤有保护作用,该作用与普瑞博斯促进胃排空有关,提示胃运动功能对胃黏膜的保护作用。     

肠三叶因子在胃黏膜应激适应性细胞保护中的作用

目的　研究肠三叶因子 (ITF ,为三叶肽家族一员 )、转化生长因子α(TGFα)及环氧合酶 2(COX 2 )在水浸束缚应激 (WRS)大鼠胃黏膜中基因表达变化 ,探讨其在胃黏膜应激适应性细胞保护中的相互关系及作用。方法　采用重复WRS制作模型 ,动态监测胃黏膜血流量 (GMBF) ,大体及光镜下观察黏膜损伤程度 (UI)及组织学变化 ,RT PCR检测ITF、TGFα及COX 2基因表达变化 ,免疫组化染色进一步证实ITF ,TGFα表达。结果　单次应激造成胃黏膜广泛损伤 ,重复应激后胃黏膜产生适应性 ,胃黏膜血流量上升 ,损伤逐渐减轻 ,4次应激后 ,损伤指数降低为单次应激的 2 1.99% ,且胃腺区细胞增殖 ,ITF、TGFα基因表达增强 (分别为 0 .0 40± 0 .0 0 1比 0 .372± 0 .0 10 ,P <0 .0 1;0 .86± 0 .0 1比 0 .93± 0 .0 1,P <0 .0 1) ,免疫组化染色证实了二者的变化趋势 ,而COX 2表达逐渐减弱 (0 .45± 0 .0 2比 0 .2 2± 0 .0 1,P <0 .0 1)。结论　胃黏膜适应性细胞保护伴有细胞增殖 ,ITF、TGFα表达水平增强及COX 2表达水平逐渐减弱 ,表明三者在这一现象中有重要的调节作用。     

乙醇对大鼠胃黏膜慢性损伤及适应性细胞的保护作用

急性乙醇摄取可引起胃黏膜糜烂、出血、甚至溃疡形成,但对长期摄取乙醇对胃黏膜的影响研究较少,同时胃黏膜在损伤后的适应性细胞保护作用尚不完全清楚.本研究应用乙醇灌胃建立大鼠慢性乙醇性胃损害模型,探讨不同时期胃黏膜病理改变特点及适应性细胞保护作用.     

一氧化氮在雷贝拉唑对大鼠胃黏膜损伤保护中的作用

目的:探讨一氧化氮(NO)在雷贝拉唑对大鼠胃黏膜损伤保护中的作用．方法:在乙醇诱导大鼠胃黏膜损伤前,预先给予雷贝拉唑(20 mg/kg)灌胃,1-硝基-精氨酸甲酯(1-NAME,4 mg／kg)、1-精氨酸(250 mg／kg)及d-精氨酸(250 mg／kg)iv．采用激光多普勒血流计(LDF)测定胃黏膜血流量(GMBF),采用镉粒还原和比色法测定胃黏膜和血浆NO-2／NO-3含量,并观察胃黏膜损伤指数(UI)、溃疡坏死组织和中性粒细胞浸润严重程度的变化．结果:与模型损伤组比,雷贝拉唑组大鼠UI明显降低(5．5±0．5 vs 25．2±2.3,P<0．01),溃疡坏死组织和中性粒细胞浸润程度明显减轻(坏死物质 → ／≤ :1／9 vs 8／2,P<0．01;中性粒细胞 → ／≤ :3／7 vs 9／1,P<0．01)．预先用1-NAME处理后,雷贝拉唑保护胃黏膜损伤作用明显减弱;1-NAME抑制作用可被1-精氨酸拮抗,而不被d-精氨酸拮抗．向胃内灌注雷贝拉唑,可增加GMBF、胃黏膜和血浆NO-2／NO-3,1-NAME可逆转这种作用,但对雷贝拉唑抑制酸分泌作用无明显影响．结论:雷贝拉唑对大鼠胃黏膜损伤保护作用与NO有关,而与雷贝拉唑抑制酸分泌作用无关．     

三叶因子1在乙醇诱导的大鼠急性胃黏膜损伤中的表达

背景:三叶因子具有胃黏膜保护作用,但其在乙醇诱导的大鼠胃黏膜损伤中黏膜保护作用的研究较少.目的:观察短期灌注不同浓度乙醇大鼠胃黏膜三叶因子(TFF)1的表达情况,探讨TFF1与胃黏膜保护的相关性.方法:采用不同浓度乙醇直接灌胃制备急性胃黏膜损伤大鼠模型,以0.9%NaCl溶液灌胃作为对照,分别在肉眼和光学显微镜下观察胃黏膜形态学变化并评估黏膜损伤指数(LI),逆转录聚合酶链反应(RT-PCR)检测大鼠胃黏膜TEF1 mRNA的表达.结果:40%、70%、100%乙醇灌胃2 h后大鼠胃黏膜LI分别为38.38±6.37、70.00±8.02和118.75±14.82,显著高于对照组(P均＜0.01).在40%乙醇和70%乙醇组大鼠胃黏膜中TFF1/β-actin光密度比值分别为1.27±0.10和1.07±0.13,显著高于对照组的0.93±0.10(P均＜0.01),100%乙醇组TFF1/β-actin光密度比值为0.68±0.09,显著低于对照组(P＜0.01).结论:胃黏膜损伤程度与乙醇浓度呈正相关,乙醇浓度越高,胃黏膜损伤越严重;一定程度的胃黏膜损伤TFF1 mRNA表达升高,严重胃黏膜损伤TFF1 mRNA表达反而下降.一定程度的损伤刺激能使TFF1产生胃黏膜保护作用.     

微米大黄炭对乙醇性急性胃黏膜损伤保护作用的实验研究

[目的]观察微米大黄炭对无水乙醇所致急性胃黏膜损伤的保护作用,探讨其可能的作用机制。[方法]将32只SD大鼠随机分为空白组、模型组、奥美拉唑镁肠溶片组和微米大黄炭组共4组,每组8只,各组给予相应浓度药物灌胃1h后,采用无水乙醇法制备大鼠急性胃黏膜损伤模型,观察各组胃黏膜损伤的大体及病理改变,测定大鼠胃组织中超氧化物歧化酶(SOD)、胃黏膜组织丙二醛(MDA)及血清前列腺素E_2(PGE_2)的表达。[结果]与模型组比较,各给药组均能减轻乙醇性急性胃黏膜损伤,降低胃黏膜病理损伤程度,升高大鼠血清PGE_2的含量,提高胃组织中SOD及PGE_2的水平,降低MDA的表达,较模型组比较差异有统计学意义(P0.01),与奥美拉唑镁肠溶片组比较差异无统计学意义。[结论]微米大黄炭可有效预防乙醇所致急性胃黏膜损伤,其机制可能与调节SOD、MDA、PGE_2等的表达有关。     

埃索美拉唑对胃黏膜的保护作用及其机制

目的:探讨埃索美拉唑对大鼠胃黏膜保护的作用及其机制.方法:在乙醇诱导大鼠胃黏膜损伤前,预先给予埃索美拉唑(20 mg/kg)灌胃,L-硝基-精氨酸甲酯(L-NAME,4 mg/kg)和L-精氨酸(250 mg/kg)iv.采用激光多普勒血流计(LDF)测定胃黏膜血流量(GMBF),镉粒还原和比色法测定胃黏膜和血浆NO-2/NO-3含量,并观察胃黏膜损伤指数(ulcer index,UI)、溃疡坏死组织和中性粒细胞浸润严重程度的变化.结果:与模型损伤组比,埃索美拉唑组大鼠UI明显降低(5.6±2.2 vs 25.3±2.4,P＜0.01),溃疡坏死组织和中性粒细胞浸润程度明显减轻(P＜0.01).预先用L-NAME处理后,埃索美拉唑保护胃黏膜损伤作用明显减弱;L-NAME抑制作用可被L-精氨酸拮抗.向胃内灌注埃索美拉唑,可增加GMBF、胃黏膜和血浆NO-2/NO-3,L-NAME可逆转这种作用,但对埃索美拉唑抑制酸分泌作用无明显影响.结论:埃索美拉唑通过NO介导对大鼠胃黏膜损伤有重要的保护作用,而与埃索美拉唑抑制酸分泌作用无关.     

西沙比利通过一氧化氮影响大鼠胃HCO_3~-分泌的实验研究

本文研究了西沙比利对大鼠胃粘膜损伤的影响和对胃粘膜—氧化氮含量分泌的影响 ,结果表明 :加入无水乙醇后 ,西沙比利 1mg/kg组胃粘膜溃疡面积及溃疡深度显著低于空白对照组 ( 10 .2± 6.9mm2 vs 2 6.1± 13.5mm2 )( 18%± 3%vs 5 0 %± 2 7% ) (P <0 .0 5 ) ,西沙比利 0 .5mg/kg组溃疡深度 ( 39%± 11% )和 2mg/kg组溃疡深度 ( 18%±7% )亦显著低于空白对照组 (P <0 .0 5 )。给予西沙比利 1mg/kg后 ,其大鼠一氧化氮 ( 2 3.32± 7.40 μmol/mg)显著高于空白对照组 ( 16.93± 3.87μmol/mg) (P <0 .0 5 )。加入西沙比利 2mg/kg后 ,大鼠胃粘膜一氧化氮含量 ( 4.35± 1.5 2μmol/mg)显著低于空白对照组 (P <0 .0 5 )。西沙比利 0 .5mg/kg组一氧化氮含量与空白对照组间差异无显著意义( 16.76± 1.0 6μmol/mg) (P >0 .0 5 )。西沙比利 1mg/kg组胃HCO3-分泌率显著升高 ( 2 0 2 %± 60 %vs 119%± 40 % )。空白对照组和西沙比利 0 .5mg/kg组无此变化。西沙比利 1mg/kg组加入无水乙醇 30分钟后HCO3-恢复率为 810 %± 2 2 0 % ,与加入无水乙醇 15分钟比较 ( 12 0 0 %± 40 0 % )差异有显著意义 (P <0 .0 5 )。西沙比利 2mg/kg组HCO3-分泌率显著降低 ( 68%± 37%vs 12 7%± 2 7% ) (P <0 .0 5 ) ,加入无水乙醇 30     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.