二苯乙烯苷预防性干预大鼠动脉硬化对其一氧化氮合酶表达的影响

目的探讨二苯乙烯苷(TSG)对动脉粥样硬化(AS)大鼠一氧化氮(NO)含量及主动脉一氧化氮合酶(NOS)表达的影响。方法SD大鼠60只,♂,随机分为6组:①正常对照组;②模型组;③TSG低剂量组;④TSG中剂量组;⑤TSG高剂量组;⑥辛伐他汀阳性对照组。造模12wk后,颈动脉取血,检测血清NO含量。取血后分离主动脉,保存于-70℃,检测主动脉组织中NOS含量,RT-PCR检测大鼠主动脉eNOS和iNOS mRNA表达。实验数据采用STATA8.0软件进行统计分析。结果与模型组相比,辛伐他汀组和TSG各剂量组均能增加血清及主动脉组织NO的含量、主动脉组织NOS的水平、主动脉组织eNOS mRNA的表达及降低主动脉组织iNOS mRNA的表达,并呈剂量依赖性。结论TSG能上调AS大鼠动脉壁eNOS mRNA的表达,抑制AS大鼠动脉壁iNOS mRNA的表达,这可能是TSG抗AS的机制之一。     

5/6肾切除对尿毒症心衰大鼠主动脉NO病理生理机制的影响研究

目的探讨5/6肾切除对尿毒症心衰大鼠一氧化氮(NO)病理生理机制的影响。方法将50只雄性SD大鼠随机分为肾切除(NX)组30只和假手术(Sham)组20只。2组常规检测血清尿素氮(BUN)、肌酐(Scr)及24h尿蛋白定量,采用Griess法测定NO含量和一氧化氮合酶(NOS)活性,实时定量聚合酶链式反应(RT-PCR)检测内皮型NOS(eNOS)和诱导型NOS(iNOS)的基因表达。结果 NX组术后第6、8周血清BUN、肌酐Scr及24h尿蛋白定量均高于Sham组;eNOS活性低于Sham组;eNOSmRNA的表达水平低于Sham组,iNOSmRNA的表达水平高于Sham组,差异均有统计学意义(P<0.05和P<0.01)。结论主动脉(包括血管内皮细胞)被损伤后,iNOS增加,而eNOS减少,从而使主动脉的舒张度降低而最终导致心衰。对于5/6肾切除大鼠,受损的主动脉NO途径可能是尿毒症诱发心衰的机制之一。     

雄激素对大鼠主动脉一氧化氮合酶/一氧化氮体系的调节

目的：研究雄激素对大鼠主动脉一氧化氮合酶／一氧化氮(NOS／NO)体系的影响，以探讨雄激素对心血管系统的作用。方法：将30只雄性大鼠随机分为三个组，每组10只，去卵巢组(A组)、去卵巢 雄激素组(B组)、假手术组(C组)。正常饮食2个月后处死大鼠，测血清雄激素、主动脉匀浆一氧化氮合酶活性及一氧化氮含量。结果：同假手术组相比。去势大鼠主动脉匀浆NOS活性及NO含量显著降低，在补充适量的雄激素后．主动脉匀浆NOS活性及NO含量显著上升。结论：雄激素可以调节大鼠动脉内一氧化氮合酶／一氧化氮体系，可能是其调节血管张力的作用机制。     

二苯乙烯苷对动脉硬化大鼠NO含量及主动脉NOS表达的影响

目的探讨二苯乙烯苷(TSG)对动脉粥样硬化(As)大鼠一氧化氮(NO)含量及主动脉一氧化氮合酶(NOS)表达的影响.方法雄性SD大鼠采用高脂饲料喂饲 维生素D3复制大鼠动脉粥样硬化模型后,灌胃TSG 120,60,30 mg·kg-1·d-1,qd,连续6周.颈动脉穿刺取血,检测血清NO含量.取血后分离主动脉,保存于-70℃,检测主动脉组织中NOS含量,RT-PCR检测大鼠主动脉内皮型一氧化氮合酶(eNOS)和诱导型一氧化氮合酶(iNOS)mRNA表达.实验设辛伐他汀2 mg·kg-1·d-1作阳性对照组.结果与模型组相比,TSG给药组呈剂量依赖性地增加血清及主动脉组织NO的含量,显著提高主动脉组织NOS的水平和eNOS mRNA的表达(P＜0.05),显著降低主动脉组织iNOS mRNA的表达(P＜0.05).TSG高剂量组的作用与辛伐他汀组相近.结论TSG抗大鼠AS的可能机制在于TSG能上调动脉壁eNOS mRNA的表达,抑制iNOSmRNA的表达.     

地高辛抗体对大鼠再灌注心肌一氧化氮合酶同工酶表达的影响

目的：观察心肌缺血再灌注（myocardial ischemia reperfusion,MIR）时大鼠心肌组织、血清NO水平及一氧化氮合酶（NOS）同工酶蛋白表达的变化和内洋地黄素特异性抗体对MIR时心肌NO系统损伤的保护作用。方法：采用左冠状动脉前降支结扎30min,复灌45min建立在体大鼠MIR模型,Sprauge-Dawley大鼠随机分成7组,每组10只：假手术组,MIR模型组,生理盐水组,维拉帕米组,小、中、高剂量地高辛抗血清组（9、18、36mg/kg）。各组于再灌注45min后立即取左室心尖部缺血区心肌并断尾取血,检测心肌匀浆和静脉血中NO含量,心肌匀浆中的内皮型一氧化氮合酶（eNOS）、诱导型一氧化氮合酶（iNOS）水平,免疫组织化学SABC法检测心肌组织eNOS、iNOS;光镜下观察心肌组织形态学变化。结果：MIR时心肌组织NO水平明显降低,但血清中NO水平无明显变化;eNOS表达明显减少,iNOS表达明显增加,心肌组织结构发生明显损伤;中、高剂量地高辛抗血清能有效降低心肌组织iNOS表达,恢复心肌细胞eNOS活性,提高心肌组织和血液中的NO水平,减轻MIR导致的心肌组织结构损伤。结论：内洋地黄素特异性抗体对MIR造成的心肌NO系统损伤具有明显的保护作用,其作用机制可能通过拮抗内洋地黄素,调节心肌NOS同工酶的表达紊乱而实现。     

地骨皮醇提物对糖尿病模型大鼠的保护作用

目的:研究地骨皮醇提物对糖尿病模型大鼠的保护作用。方法:高脂饲料喂养4周后腹腔注射链脲佐菌素以复制大鼠糖尿病模型。50只SD大鼠随机均分为正常对照(等容生理盐水)组、模型(等容生理盐水)组与地骨皮醇提物高、中、低剂量(40、20、10 g/kg)组,灌胃给药,每天1次,连续4周。测定超氧化物歧化酶(SOD)、丙二醛(MDA)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、一氧化氮(NO)水平,观察大鼠主动脉血管形态学,实时荧光定量聚合酶链反应(RT-PCR)法测定诱导型一氧化氮合酶(iNOS)、内皮型一氧化氮合酶(eNOS)mRNA的表达。结果:与正常对照组比较,模型组大鼠SOD活性减弱,NO含量减少,MDA含量增加,ALT、AST活性增强,eNOS mRNA表达减弱,iNOS mRNA表达增强,差异有统计学意义(P<0.01);大鼠主动脉血管形态学呈病理状态。与模型组比较,地骨皮醇提物高、中剂量组大鼠SOD活性增强,NO含量增加,MDA含量减少,ALT、AST活性减弱,iNOS mRNA表达减弱,eNOS mRNA表达增强,差异有统计学意义(P<0.01或P<0.05);大鼠主动脉血管形态学病理状态得到一定改善。结论:地骨皮醇提物对糖尿病模型大鼠有一定保护作用。     

氯沙坦对糖尿病大鼠肾皮质血管紧张素Ⅱ2型受体及诱生型一氧化氮合酶基因表达的影响

目的 研究氯沙坦对糖尿病大鼠肾组织血管紧张素系统与一氧化氮系统的影响及其二者之间的关系。方法 SD大鼠随机分成3组：对照组、糖尿病组和氯沙坦（30 mg·kg^-1·d^-1×8周, ig）治疗组。应用RT-PCR技术检测大鼠肾皮质血管紧张素Ⅱ2型受体(AT₂)、Ⅳ型胶原及诱生型一氧化氮合酶（iNOS）mRNA表达。并同时检测大鼠肾皮质血管紧张素Ⅱ(AngⅡ)、NO含量及一氧化氮合酶（NOS）活性。结果 糖尿病组大鼠尿蛋白排泄率、肾皮质AngII含量、Ⅳ型胶原mRNA及iNOS mRNA表达较对照组明显升高；糖尿病大鼠肾皮质NOS活性也较对照组明显增强；然而糖尿病大鼠肾皮质NO含量及AT₂ mRNA水平却较对照组大鼠明显降低；氯沙坦治疗能显著降低糖尿病大鼠尿蛋白排泄率及肾皮质Ⅳ型胶原mRNA表达；并能明显增加肾皮质AT₂及iNOS mRNA表达及总NOS活性及NO含量。结论 AT₂的激活与氯沙坦的肾脏保护作用有关，并可能参与了对肾脏iNOS mRNA表达的上调。     

银杏叶提取物对糖尿病大鼠一氧化氮水平的影响

目的研究银杏叶提取物(EGb)对糖尿病大鼠心肌、睾丸、脑组织一氧化氮水平的影响。方法用链脲佐菌素制备SD大鼠糖尿病模型。测定EGb对糖尿病大鼠心肌、睾丸、脑组织一氧化氮(NO)的含量及一氧化氮合酶(NOS)、诱导型一氧化氮合酶(iNOS)、结构型一氧化氮合酶(cNOS)的活性的影响。结果与正常组相比,糖尿病大鼠心肌、睾丸组织NO含量及NOS、iNOS活性升高,脑组织NO含量及NOS活性升高。与糖尿病组相比,EGb治疗组大鼠心肌、睾丸组织NO含量及NOS、iNOS活性下降。结论EGb能够对抗糖尿病大鼠过量NO对心肌、睾丸组织的损伤。     

葛根素对高胰岛素环境下大鼠肝细胞一氧化氮合成的影响

目的：观察葛根素对高胰岛素环境下大鼠肝细胞一氧化氮（NO）合成的影响。方法：体外培养BRL大鼠肝细胞株，用高胰岛素诱导其形成胰岛素抵抗细胞模型，观察葛根素对肝细胞一氧化氮合成的影响。结果：葛根素可调节高胰岛素环境下大鼠肝细胞一氧化氮合酶（NOS）的活性，增加肝细胞NO的合成。结论：葛根素可通过适度调节肝细胞NO的产生，从而促进肝细胞对葡萄糖转化，改善肝细胞胰岛素抵抗的作用。     

氯沙坦对糖尿病大鼠肾皮质血管紧张素Ⅱ2型受体及诱生型一氧化氮合酶基因表达的影响

目的研究氯沙坦对糖尿病大鼠肾组织血管紧张素系统与一氧化氮系统的影响及其二者之间的关系。方法SD大鼠随机分成3组:对照组、糖尿病组和氯沙坦(30 m.gkg-1.d-1×8周,ig)治疗组。应用RT-PCR技术检测大鼠肾皮质血管紧张素Ⅱ2型受体(AT2)、Ⅳ型胶原及诱生型一氧化氮合酶(iNOS)mRNA表达。并同时检测大鼠肾皮质血管紧张素Ⅱ(AngⅡ)、NO含量及一氧化氮合酶(NOS)活性。结果糖尿病组大鼠尿蛋白排泄率、肾皮质AngII含量、Ⅳ型胶原mRNA及iNOS mRNA表达较对照组明显升高;糖尿病大鼠肾皮质NOS活性也较对照组明显增强;然而糖尿病大鼠肾皮质NO含量及AT2mRNA水平却较对照组大鼠明显降低;氯沙坦治疗能显著降低糖尿病大鼠尿蛋白排泄率及肾皮质Ⅳ型胶原mRNA表达;并能明显增加肾皮质AT2及iNOS mRNA表达及总NOS活性及NO含量。结论AT2的激活与氯沙坦的肾脏保护作用有关,并可能参与了对肾脏iNOS mRNA表达的上调。     

急性一氧化碳中毒心肌损害的探讨

目的探讨急性一氧化碳（CO）中毒对心肌的损害,使急性CO中毒患者得到更全面的治疗。方法分析急性CO中毒153例患者的临床表现、心电图及心肌酶改变。结果153例急性CO中毒患者中86.3%出现昏迷,13.7%出现心力衰竭,随机将其中65例中毒患者作心电图及心肌酶检查,发现86.2%出现心电图改变,67.7%出现心肌酶改变。结论急性CO中毒不仅对神经系统造成损害,对心肌的损害也很严重,需要给予相应的治疗。     

纳洛酮治疗急性一氧化碳中毒

目的：探索纳洛酮对急性一氧化碳中毒的疗效。方法：治疗组２１例（男性１６例，女性５例；年龄３９±ｓ１９ａ）除常规治疗外，加用纳洛酮１．２～１．６ｍｇ溶于５％葡萄糖２０ｍＬ中静脉推注，ｑｈ，直至病人清醒；对照组２０例（男性１５例，女性５例，年龄４１±２０ａ）用纠正缺氧、预防脑水肿、保持呼吸道通畅等常规治疗。结果：治疗组与对照组平均促醒时间对中度中毒分别为１．２±０．４ｈ和２．６±０．６ｈ（Ｐ＜０．０１），重度中毒分别为８．７±１．２ｈ和１３±４ｈ（Ｐ＜０．０５）。结论：纳洛酮在急性一氧化碳中毒的治疗上有效。     

Carbon monoxide poisoning during camping in Korea

Objective: The aim of this study was to evaluate the epidemiology and characteristics of unintentional carbon monoxide (CO) poisoning during camping in Korea.

Methods: We performed a retrospective observational study on patients with unintentional camping-related CO poisoning who were admitted to the emergency department (ED) from 1 January 2010 to 31 December 2014. News reports about incidents of camping-related CO poisoning were collected using news search engines.

Results: A total of 72 patients (29 patients involved in 12 incidents, who were admitted to our ED, and 43 victims involved in 17 incidents reported in the media) were identified. Accidental camping-related CO poisoning occurred most frequently in May, late spring in Korea. Gas stove use and the burning of charcoal for tent heating were responsible for camping-related CO exposure. Seventeen victims (39.5%) were found dead when an ambulance arrived at the scene, in the cases reported in the media. In contrast, all the victims at our hospital were alive on hospital discharge. Twelve of the 17 incidents (70.6%) reported in the media were accidental fatalities. The majority of our patients (83.4%) were not aware of the potential danger of charcoal as a source of CO.

Conclusion: Accidental camping-related CO poisoning occurred because of an ongoing lack of awareness about the potential danger of charcoal grills and stoves, and this caused prehospital mortality. Such accidents could be prevented by increasing the awareness of the potential danger of using charcoal grills and stoves during camping, as well as by establishing appropriate safety regulations.     

Carbon monoxide as a novel central pyrogenic mediator

Carbon monoxide (CO) are produced by heme oxygenase (HO), and HO was detected in hypothalamus. However, the roles of CO produced in hypothalamus was not fully elucidated. So, we tested the effects of CO on body temperature because preoptic-anterior hypothalamus was known as the presumptive primary fever-producing site. CO-saturated aCSF (4 microl, i.c.v.) and hemin (10 microg, i.c.v.) elicited marked febrile response. Pretreatment with indomethacin completely inhibited CO- and hemin-induced fever. Zinc protoporphyrin-IX (10 microg, i.c.v.) or ODQ (50 microg, i.c.v.) partially reduced hemin-induced febrile response. Dibutyryl-cGMP (100 microg, i.c.v.) produced profound febrile response and this febrile response was attenuated by indomethacin. These results indicate that endogenous CO may have a role as a pyrogenic mediator in CNS and CO-mediated pyresis is dependent on prostaglandin production and partially on activation of soluble guanylate cyclase.     

Xanthine oxidoreductase and neurological sequelae of carbon monoxide poisoning

Neurological sequelae (NS) is a common complication of carbon monoxide (CO) poisoning and structural alterations of myelin basic protein have been proven to initiate immunological reactions leading to NS. To determine whether xanthine oxidoreductase (XOR) participates in the pathophysiology of CO-mediated NS, we examined myelin basic protein in CO poisoned XOR-depleted rats and performed radial maze studies to evaluate the alteration of cognitive function. Carbon monoxide poisoned XOR-depleted rats did not exhibit myelin basic protein alterations or impaired cognitive function, both found in CO poisoned control rats. These results indicate that XOR is essential to the pathological cascade of CO-mediated NS.     

Therapeutic applications of the gaseous mediators carbon monoxide and hydrogen sulfide

Background: Hydrogen sulfide (H₂S) and carbon monoxide (CO) are endogenously produced gaseous autacoids that regulate a number of physiological processes, including the inflammatory response, cell death and proliferation, neural transmission and smooth muscle tone. Objective/methods: The current review aims to provide a comprehensive overview of all recent patent applications that address the potential therapeutic applications of CO and H₂S. Results/conclusion: Beyond the direct administration of CO and H₂S, this review highlights the therapeutic applications of a variety of gas-releasing molecules that are being developed to deliver CO and H₂S to diseased tissues at therapeutic doses. The term autacoid, which, in addition to its pharmacological use to describe a locally-acting hormone, literally translates from Greek as ‘self-drug’, seems to particularly well describe the current approach to capture the potential therapeutic use of these two gasotransmitters. In summary, we can conclude that there is a markedly growing interest in harnessing the tissue-protective actions of CO and H₂S.     

Noninvasive measurement of carbon monoxide levels in ED patients with headache

Objectives

Carbon Monoxide (CO), the third most common cause of acute poisoning death, is easily overlooked in the emergency department (ED). Nonspecific complaints such as headache, weakness, or malaise may easily result in misdiagnosis. The objectives of this study are to determine the frequency of CO poisoning in patients presenting to the ED complaining of headaches and to determine the feasibility of using noninvasive CO analyzers as a screening tool.

Methods

This prospective controlled study examined, during the winter months, adult patients presenting with a complaint of atraumatic, afebrile headaches. All subjects submitted a sample for a CO breath analyzer. Participants with elevated carboxyhemoglobin (COHb) levels (nonsmoker > 2%, smokers > 5%) underwent venous COHb testing. Control patients, without headaches, presenting to the ED were similarly studied.

Results

We enrolled 170 subjects and 98 controls. Of the 170 subjects, 12 (7.1%) had elevated COHb levels confirmed by venous COHb levels. Of the 98 controls, 1 (1.0%) had an elevated COHb level (p<0.05). There were no differences in demographic factors between the two groups (p > 0.16).

Conclusions

Noninvasive measurement of CO levels in ED patients with headaches is rapid and specific. During winter months, elevated CO levels are present in over 7% of ED patients with headaches.     

一氧化碳中毒迟发性脑病的临床分析

目的分析探讨一氧化碳中毒后迟发性脑病的发病特征与机制,总结临床诊治经验。方法收集我院2007年1月至2011年1月期间因急性一氧化碳中毒迟发性脑病住院的患者共76例,对其临床资料进行回顾性调查分析。结果患者有众多临床表现:精神淡漠、痴呆、小便失禁、缄默、偏瘫、癫痫发作等;76例患者治疗后经疗效判定,其中治愈24例,显效26例,好转12例,无效14例,总有效率为81.6%。结论 DEACMP发病机制尚不明了,临床表现众多,影像学检查有助于提高对患者的诊断,减少误诊率,给予患者及时、足疗程的治疗可最大限度的促进患者预后。     

蝮蛇抗栓酶治疗急性一氧化碳中毒性痴呆

急性一氧化碳中毒性痴呆１９例，男性１１例，女性８例，年龄６２±ｓ７ａ，用精制蝮蛇抗栓酶较大剂量治疗，１．０Ｕ于生理盐水５０ｍＬ，ｉｖ，ｂｉｄ，１０ｄ为一个疗程，共用６个疗程。结果痊愈１６例，显著进步２例，无效１例，总有效率为９５％。