17α—羟化酶缺陷症的诊断和治疗—13例临床经验

在先天性肾上腺皮质增生症中，１７α－羟化酶缺陷症（１７α－ＨＤ）很少见，截至１９９１年，在国外文献中只收集到１２０例，至今国内文献能查到的８例报告，作者总结了自１９７８年至１９９２年期间收治的１３例１７α的临床资料，对诊断和治疗进行了讨论。     

HCV和HIV-1合并感染标本中HCV基因分型

目的了解丙型肝炎病毒（ＨＣＶ）和人类免疫缺陷病毒Ｉ型（ＨＩＶ－１）混合感染标本中ＨＣＶ基因型情况。方法采用了根据ＨＣＶ５′端非转译区基因组所设计的反相探针杂交测定方法（ＩＮＮＯＬｉＰＡ，ＨＣＶⅡ），对来自六个地区的１７份抗－ＨＣＶ和抗－ＨＩＶ－１双阳性标本进行ＨＣＶ基因型分型研究。结果在１７份标本中，７份（４１．１８％）为Ｉ（１ｂ）型病毒，５份（２９．４１％）为Ⅱ（２ａ／２ｃ）型病毒，５份（２９．４１％）为Ｉ型（１ｂ）和Ⅱ（２ａ／２ｃ）混合型病毒。结论发现ＨＣＶ与ＨＩＶ－１合并感染标本中存在Ｉ（１ｂ）型、Ⅱ（２ａ／２ｃ）型以及Ｉ（１ｂ）型与Ⅱ（２ａ／２ｃ）型混合型ＨＣＶ。值得注意的是对α－干扰素治疗不敏感并且较易趋于导致严重的慢性肝炎、肝硬化和肝细胞癌的Ⅱ型ＨＣＶ感染的比率占７０．５８％（１２／１７）。     

“急性非甲非乙型”肝炎的病原学分析

对抗－ＨＡＶ－ＩｇＭ、ＨＢｓＡｇ和抗－ＨＢｃ－ＩｇＭ均（一）、临床诊断为急性非甲非乙肝炎７２例进一步病原学鉴定。以聚合酶链反应检出乙型和丙型肝炎病毒；血清学包括酶免疫法检测抗－ＨＣＶ、抗－ＨＤＶ－ＩｇＭ、抗ＨＥｖ－ＩｇＧ（Ｇｅｎｅｌａｂｓ）、抗－ＣＭＶ－ＩｇＭ和抗－ＥＢＶ－ＩｇＭ。结果诊断丙型肝炎１７例（２３．６％），戊型肝炎１４例（１９．５％），最多的竟是慢性无症状ＨＢＶ感染的急性活动（３４例，４７．２％），其中合并ＨＣＶ例、ＨＤＶｌ例、ＨＥＶ１０例和自发性活动１７例。因而，我国“急性非甲非乙”肝炎的病原学可能相当复杂。     

应用丁型肝炎病毒27肽抗原检测丁型肝炎病毒抗体

采用中科院上海生化所合成丁型肝炎病毒（ＨＯＶ）抗原２７肽酶联法，检测重庆地区乙型肝炎病毒（ＨＢＶ）感染者中血清丁型肝炎病毒抗体（抗－ＨＤ）结果：３００例献血员中１例阳性（此人ＡＬＴ较正常升高２倍）１１３例甲型肝炎、５８例非乙型肝炎均为阴性；ＨＢＶ标记阳性者８８２例中抗－ＨＤ（＋）１０６例（１２．０２％），其中乙型肝炎表面抗原携带者１３／４１０例（３．１７％）、急性肝炎１１／７６例（１４．４％）、慢性迁延性肝炎１／１３例（７．６９％）、慢性活动性肝炎２２／１２１例（１７．６８％）、重型肝炎１７／８６例（１９．７７％）、肝硬化２３／７８例（２９．４９％）、原发性肝细胞癌１９／９８例（１９．３９％）。结果与已往报告基本一致。与ＡｂｂｏｔｔＥＩＡ试剂相符率为７４／７８例（９４．９％）。采用天然丁型肝炎病毒抗原（ＨＯＡｇ）与之竞争抗－ＨＤ，４份阳性转为阴性，２份阴性结果不变，提示本ＨＤＶ抗原合成肽具有天然ＨＤＡｇ活性，可特异识别抗－ＨＤ，是一新的、稳定、安全、可靠的诊断用试剂。     

慢性肝病组织中肿瘤坏死因子α的免疫组化研究

用免疫过氧化物酶技术对３例慢迁肝、５例慢活肝和１７例肝硬化组织及７例正常肝组织作肿瘤坏死因子α单克隆抗体免疫组化研究。发现慢性肝病组织内肝细胞、浸润单核细胞和胆管上皮细胞合成大量肿瘤坏死因子α（ＴＮＦ－α）且主要分布在汇管区和坏死区周围，其含量与组织内炎症活动指数（ＨＡＩ）密切相关。提示ＴＮＦ－α可能与慢性肝脏损害和肝纤维化有关。     

17α-羟化酶缺陷及其分子基础

先天性肾上腺增生（ＣＡＨ）是由于肾上腺类固醇激素合成过程中酶的缺陷所导致的一组疾病，它涉及几种不同的细胞色素Ｐ４５０：Ｐ４５０ｓｃｃ，Ｐ４５０ｃ２１，Ｐ４５０１１β，Ｐ４５０ｃ１７α及３β－羟化类固醇脱氢酶，属常染色体隐性遗传病。１７α－羟化酶缺陷是...     

病毒性肝炎患者523例HCV与HAV,HBV重叠感染的临床分析

本文对５２３例各型病毒性肝炎患者进行丙型肝炎抗体（抗－ＨＣＶ）检测，阳性率为１１．６６％（６１／５２３）。抗－ＨＣＶ阳性者与ＨＡＶ和ＨＢＶ重叠感染率分别为２９．５１％和６２．３０％。急性肝炎有１７例重叠ＨＡＶ感染（１７／２６）。慢性肝炎和肝硬化重叠感染ＨＢＶ２４例（２４／２８），重型肝炎７例均重叠感染ＨＢＶ（７／７）。未发现重叠感染对ＨＢＶ复制的干扰抑制现象。     

重组干扰素治疗慢性丙型肝炎疗效评价

本文报道了２９例慢性丙型肝炎（ＣＨＣ）患者采用重组α－干扰素（α－ＩＦＮ）每日６００万单位，疗程８周，于治疗前，治疗后即刻、３个月、６个月或１年，２年采集血清，测定丙型肝炎病毒核酸（ＨＣＶＲＮＡ）并动态观察其丙氦酸转氨酶（ＡＬＴ）的变化。结果表明：１２例（４１．４％）呈持续应答，ＨＣＶＲＮＡ持续阴转２年以上，ＡＬＴ亦持续正常；９例（３１．ｏ％）呈暂时应答；８例（２７．６％）为无应答反应。并提示血液中含有高滴度ＨＣＶＲＮＡ的ＣＨＣ患者可能对干扰素治疗较为敏感。     

抗-HBs、抗-HBc阳性的临床意义

抗－ＨＢｓ、抗－ＨＢｃ阳性的临床意义山东省立医院（２５００２１）任万华赵洪涛近年来，我们在进行健康查体时发现４７例抗－ＨＢｓ、抗－ＨＢｃ阳性者（男３８例、女９例，年龄１７～４２岁），当时查肝功能均正常，且无临床症状。为了解此类人群的转归，我们对其进行...     

病毒性肝炎和肝硬化患者IL－6、TNF－α的变化

为研究白细胞介素－６（ＩＬ－６）、肿瘤坏死因子（ＴＮＦ－α）在肝炎和肝硬化（ＬＣ）患者中的作用。检测了１５例正常人，１８例急性病毒性肝炎（ＡＨ），３７例慢性肝炎（ＣＨ），２０例ＬＣ患者血清及外周血单个核细胞（ＰＢＭＣ）的ＩＬ－６、ＴＮＦ－α水平。结果以ＣＨ患者ＩＬ－６、ＴＮＦ－α水平最高（血清及ＰＢＭＣ的ＩＬ－６水平分别为７２．１±３２．９４Ｕ／ｍｌ，１４０．７±３３．５Ｕ／ｍｌ；血清及ＰＢＭＣ的ＴＮＦ－α水平为３．９７±１．３８ｎｇ／ｍｌ，６．３５±１．４１ｎｇ／ｍｌ）。恢复期或稳定期ＴＮＦ－α和ＩＬ－６水平明显低于急性期或活动期（Ｐ＜０．０１）。ＣＨ患者肝组织学活动指数（ＨＡＩ）分数与ＰＢＭＣＩＬ－６和ＴＮＦ－α水平呈正相关（γ分别为０．８９，０．６８；Ｐ＜０．０５）。提示ＩＬ－６和ＴＮＦ－α是肝脏损害重要的炎症介质，介导肝细胞损害。     

5-HD abolishes ischemic preconditioning independently of monophasic action potential duration in the heart

Objective: Blocking of the K_ATP channel with either glibenclamide or 5-hydroxydecanoate (5-HD) has been shown to abolish the infarct reducing effect of ischemic preconditioning (IPC) in hearts from several species, but the results in rat and rabbit have been equivocal. In this study we investigated if 5-HD could abolish IPC in rat and rabbit and further if IPC or IPV + 5-HD were affecting action potential duration in the rabbit heart. Methods: The rat hearts were isolated and retrogradely perfused on a Langendorff perfusion apparatus with Krebs-Henseleit buffer. The rabbit experiments were performed in an in situ model. Rat and rabbit hearts were subjected to 30 min regional ischemia by ligating a coronary artery followed by 120 min (rat) or 150 min (rabbit) of reperfusion. The preconditioning protocol was one or three cycles of 5 min ischemia plus 5 min reperfusion in the rat and one cycle of 5 min ischemia plus 10 min reperfusion in the rabbit. In the rat 5-HD was added to the reservoir before ischemic preconditioning in different concentrations, and in the rabbit 5-HD was given as a bolus 5 mg/kg intraventricularly 2 min before the preconditioning ischemia. In the rabbit epicardial monophasic action potential duration at 50% repolarization (MAPD₅₀) was measured at 1, 2 and 5 min in each of the ischemic periods using a contact pressure electrode. Infarcts were measured with tetrazolium staining and risk zone volumes with fluorescent microspheres. Results: All data are presented as infarct size in % of risk zone volume (mean ± SEM). In the rat 200 μM of 5-HD abolished the protective effect of one cycle of IPC (28.6 ± 4.7 versus 8.4 ± 0.8) and 500M of 5-HD abolished three cycles of IPC (50.7 ± 7.8 versus 8.4 ± 2.0). Control was 40.9 ± 2.8. In the rabbit 5-HD abolished IPC (41.2 ± 7.2 versus 8.1 ± 3.2). Control was 53.5 ± 12.4. MAPD₅₀ were significantly more shortened compared to control at 1 and 2 min into the 30 min ischemia for the IPC and IPC+5-HD. Conclusions: We conclude that 5-HD abolishes ischemic preconditioning when given before the preconditioning ischemia in both rat and rabbit but does not abolish into ischemia induced shortening of the action potential duration in the rabbit; thus, a role for the mitochondrial K_ATP channel and not the sarcolemmal K_ATP channel in the protective mechanism behind IPC is probable. Received: 15 July 1999, Returned for 1. revision: 17 August 1999, 1. Revision received: 13 September 1999, Returned for 2. revision: 12 October 1999, 2. Revision received: 3 November 1999, Accepted: 17 November 1999     

Cytochrome P450 omega-hydroxylase inhibition reduces infarct size during reperfusion via the sarcolemmal KATP channel

Inhibition of 20-hydroxyeicosatrienoic acid (20-HETE), by pretreatment with pharmacological inhibitors of cytochrome P450 (CYP) omega-hydroxylase, has been shown to reduce infarct size in canines when administered prior to ischemia. However, it is unknown whether these agents reduce infarct size when administered just prior to reperfusion and if the sarcolemmal and/or mitochondrial K(ATP) channels (sK(ATP) and mK(ATP)) contribute to cardioprotection. Therefore, we determined whether specific CYP inhibitors for epoxygenases and omega-hydroxylases are cardioprotective when given either prior to ischemia or prior to reperfusion and furthermore, if selective inhibition of the sK(ATP) by HMR-1098 or mK(ATP) by 5-hydroxydecanoic acid (5-HD) could abrogate this effect. Male Sprague-Dawley rats underwent 30 minutes of ischemia followed by 2 hours of reperfusion. Groups received either miconazole (MIC, non-selective CYP inhibitor, 3 mg/kg), 17-octadecynoic acid (17-ODYA, CYP omega-hydroxylase inhibitor, 0,3 or 3 mg/kg), N-methylsulfonyl-12, 12-dibromododec-11-enamide (DDMS, CYP omega-hydroxylase inhibitor, 0,4 or 4 mg/kg), N-methanesulfonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH, CYP epoxygenase inhibitor, 3 mg/kg), or vehicle either 10 minutes prior to ischemia or 5 minutes prior to reperfusion. Rats also received either HMR-1098 (6 mg/kg) or 5-HD (10 mg/kg) 10 minutes prior to reperfusion, with subsets of rats also receiving either MIC or 17-ODYA 5 minutes prior to reperfusion. DDMS and 17-ODYA dose dependently reduced infarct size. Rats treated with MIC, 17-ODYA and DDMS, but not MS-PPOH, produced comparable reductions in infarct size when administered prior to ischemia or reperfusion compared to vehicle. HMR-1098, but not 5-HD, also blocked the infarct size reduction afforded by MIC and 17-ODYA. These data suggest a novel cardioprotective pathway involving CYP omega-hydroxylase inhibition and subsequent activation of the sK(ATP) channel during reperfusion.     

Cardioprotective effects of 17 beta-estradiol produced by activation ofmitochondrial ATP-sensitive K(+)Channels in canine hearts

We have previously demonstrated the effects of estrogen on modulation of myocardial ATP-sensitive K(+)(K(ATP)) channel. Previous studies have demonstrated that activation of mitochondrial K(ATP)channel is a major contributor of ischemic cardioprotection. The purpose of the present study was to investigate the role of K(ATP)channel in estrogen-induced myocardial protection after ischemia/reperfusion in dogs. Anaesthetized dogs were subjected to 60 min of left anterior descending coronary artery occlusion followed by 2 h of reperfusion. In a first study to characterize effects of sex and the dose-response profile of estrogen on infarct size, the drug was intravenously administered at 10 or 20 microg/kg. In a second study to investigate the cardioprotective mechanisms of estrogen, vehicle, preconditioning or 17 beta -estradiol (10 microg/kg) was given, beginning 15 min prior to the 60 min occlusion period in the presence or absence of 5-hydroxydecanoate (5-HD). In the first study, administration of 17 beta -estradiol resulted in a significant, dose-dependent limitation of infarct size. Estrogen administration provided myocardial protection of similar magnitude in both males and females. In the second study, infarct size in control animals averaged 39+/-5% of the risk region, compared with 14+/-5% of the risk region in estrogen-treated dogs and 6+/-5% of the risk region in preconditioning dogs (both P<0.0001 v controls). Pretreatment with 5-HD completely abolished preconditioning- and estrogen-induced cardioprotection. Estrogen limits myocardial infarction size resulting from coronary artery occlusion and reperfusion in a dose-dependent fashion, irrespective of gender difference. The infarct size-limiting effect of estrogen++ was abolished by 5-HD, suggesting that the cardioprotective effect of estrogen may result from activation of myocardial mitochondrial K(ATP)channels.     

ATP-sensitive K+ channels mediate the delayed cardioprotective effect of adenosine A1 receptor activation.

Adenosine A1 receptor stimulation increases myocardial resilience to ischaemia many hours later but the mechanism of protection is unclear. We hypothesized that A1 receptor-induced delayed cardioprotection is mediated by KATP channel opening. Rabbits were pretreated with saline or the selective A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA), 0.1 mg/kg i.v. After 24 h, they were anaesthetized and subjected to 30 min left coronary artery occlusion (CAO) and 120 min reperfusion. Twenty minutes before CAO, either glibenclamide 0.3 mg/kg, sodium 5-hydroxydecanoate (5-HD) 5 mg/kg, or a corresponding volume of vehicle solution were given i.v. Infarct size as a percentage of ischaemic risk volume (I/R%) was assessed by triphenyltetrazolium. In the absence of either glibenclamide or 5-HD, CCPA pretreatment resulted in significant limitation of infarction (I/R 23.4+/-3.3%vs 39.6+/-2.6% in saline pretreated animals, P<0.01). Administration of glibenclamide before CAO abolished this delayed protective effect of CCPA (I/R 37.4+/-4. 7%), as did 5-HD (I/R 48.8+/-3.7%). Neither glibenclamide nor 5-HD significantly modified I/R in saline pretreated animals. Risk volume was similar in all groups (0.8-1.1 cm3). Systemic haemodynamic variables were not markedly different between any of the groups immediately before or during the ischaemia-reperfusion protocol. Thus, delayed protection following transient A1 receptor activation was abolished by pre-ischaemic treatment with either glibenclamide or 5-HD, providing pharmacological evidence that KATP channel opening mediates A1 agonist-induced delayed myocardial protection. The inhibitory effect of 5-HD suggests specific involvement of mitochondrial KATP but the mechanisms of sub-acute regulation of KATP function following A1 receptor stimulation remain to be determined.     

Mito-KATP对缺氧复氧大鼠心肌微血管内皮细胞凋亡的影响及作用机制

目的探讨线粒体ATP敏感性钾通道(mito-KATP)开放影响缺氧复氧大鼠心肌微血管内皮细胞(MMECs)凋亡的作用机制。方法培养大鼠心肌微血管内皮细胞,随机分为四组:对照组(N组)、模型组(H/R组)、开放剂组(DZ组)、阻断剂组(5-HD组)。DZ组加入100μmol/L二氮嗪预处理2 h,5-HD组在加入100μmol/L二氮嗪前,先用100μmol/L 5-羟葵酸预处理2 h,然后上述两组和H/R组同样进行缺氧2 h复氧2 h。Hoechst染色方法观察凋亡细胞形态,Annexin V-FITC/PI双标记法测定各组细胞凋亡率、RT-PCR法检测各组NF-κB、FKN和p53 mRNA转录水平。结果与N组比较,H/R组可见大量细胞坏死、脱落,细胞凋亡率升高(P<0.01),NF-κB、FKN和p53 mRNA表达上调(P<0.01);与H/R组比较,DZ组可见部分细胞坏死脱落,细胞凋亡率降低(P<0.01),NF-κB、FKN和p53 mRNA表达下调(P<0.01);5-HD组与H/R组比较无显著差异。结论 mito-KATP开放可抑制缺氧复氧所致MMECs凋亡,其机制可能与抑制NF-κB、FKN及p53 mRNA表达有关。     

Blockade of ATP-sensitive potassium channels by 5-hydroxydecanoate suppresses monophasic action potential shortening during regional myocardial ischemia

Summary We tested 5-hydroxydecanoate (5-HD), a specific blocker of ATP-sensitive potassium channels (IK.ATP), to determine if it mitigates electrophysiologic changes produced by regional myocardial ischemiain vivo. A sequence of 5-minute occlusion of the distal LAD and 30-minute reperfusion was repeated while recording the monophasic action potential (MAP) and bipolar electrogram (EG) from the epicardial center of the ischemic myocardium in anesthetized dogs. 5-HD (30 mg/kg, IV) or glibenclamide (0.15 or 0.3 mg/kg, IV) was administered before the third occlusion, and the data were compared to the second occlusion data. 5-HD did not affect baseline MAP duration at 90% and 50% repolarization (APD90, APD50) before LAD occlusion but suppressed occlusion-induced shortening of APD90 (16 ± 2% during the second occlusion vs. 5 ± 3% during the third occlusion, n=8, p<0.01) and APD50 (16 ± 3% vs. 10 ± 3%, n=8, p<0.05). Pretreatment with glibenclamide also suppressed occlusion-induced MAP shortening and eliminated an additional effect of 5-HD (n = 3). 5-HD did not affect the occlusion-induced increase in duration and activation time of EG. 5-HD, as well as glibenclamide, suppressed regional ischemia-induced MAP shortening, probably by blocking activation of IK.ATP, without affecting conduction delay. These differential effects of 5-HD on repolarization and conduction during the early phase of regional ischemia might have the potential to suppress reentrant ventricular arrhythmias.This study was supported in part by Mitsukoshi Prize of Medicine 1993 (Satoshi Ogawa, Toshihisa Miyazaki).     

庚醇预处理的心脏保护作用对细胞膜缝隙连接蛋白43的影响

目的探讨庚醇预处理对家兔心肌缺血再灌注损伤的作用及其机制。方法将50只新西兰大白兔随机分为5组:假手术组、缺血再灌注组(IR组)、缺血预处理组(IP组)、庚醇预处理组(HP组)、庚醇预处理加5-羟葵酸(5-HD)预处理组(HP+5-HD组),每组10只。所有新西兰大白兔再灌注4h后处死。分别于术前、缺血时、再灌注2、4h检测血浆肌酸激酶同工酶和心肌肌钙蛋白活性;采用免疫荧光标记检测Cx43。结果与IR组比较,IP组及HP组心肌坏死区/左心室范围明显降低(P<0.01)。与假手术组比较,IR组、HP+5-HD组Cx43mRNA表达明显降低(P<0.01);与HP+5-HD组比较,IP组、HP组Cx43mRNA表达明显升高(P<0.01);与IR组比较,IP组、HP组、HP+5-HD组Cx43mRNA表达明显升高(P<0.05,P<0.01)。结论庚醇预处理可以通过衰减由心肌缺血再灌注诱导的细胞膜Cx43表达下降,对损伤心肌起到保护作用。     

阿托伐他汀预处理对心肌保护作用的实验研究

目的观察阿托伐他汀（ATV）预处理的心肌保护效应,探讨诱导型一氧化氮合酶（iNOS）和线粒体膜ATP敏感性钾通道（KATP）在其中的作用以及这两个环节的相互关系。方法将兔随机分成缺血再灌注模型对照组（对照组）、ATV组、ATV复合iNOS阻断剂S-甲基异琉脲硫酸盐组（ATV＋SMT组）、S-甲基异琉脲硫酸盐组（SMT组）、ATV复合线粒体膜KATP通道阻断剂5-羟癸酸组（ATV＋5-HD组）、5-羟癸酸组（5-HD）组。进行40min局部缺血和240min再灌注,观察各组心肌梗死范围、血液生物化学、一氧化氮合酶、线粒体ATP合成能力。结果3天阿托伐他汀预处理（10mg·kg^-1·d^-1）使心肌梗死范围、肌酸激酶同工酶（CK—MB）、乳酸脱氢酶同工酶（LDH-1）分别下降26．3％、31．4％、19．1％,使iNOS、线粒体ATP合成能力分别提高102．6％和46．8％。ATV＋SMT组心肌梗死范围、CK-MB、LDH-1、iNOS、线粒体ATP合成能力和对照组无明显差异。ATV＋5-HD组心肌梗死范围、CK-MB、LDH-1、线粒体ATP合成能力和对照组无明显差异,ATV＋5-HD组iNOS和ATV组相似,均明显高于对照组（P〈0．01）。结论阿托伐他汀预处理通过上调iNOS和激活线粒体膜KATP产生心肌保护作用,且iNOS是线粒体膜KATP的上游途径。     

The cardioprotective effect of uridine and uridine-5'-monophosphate: the role of the mitochondrial ATP-dependent potassium channel

The activity of mitochondrial ATP-dependent potassium channel (mitoKATP) of rat heart and liver mitochondria was shown to decrease during aging. This partially explains the increase of risk of ischemia at a mature age since mitoKATP activation provides cardioprotection. We demonstrated that uridine-5'-diphosphate (UDP) possesses the property to activate mitoKATP. At a concentration of 30 microM, it reactivated mitoKATP in mitochondria, and 5-hydroxydecanoate (5-HD) eliminated this effect. In experimental animals, UDP precursors uridine and uridine-5'-monophosphate (UMP) (both 30 mg/kg, administered intravenously 5 min before coronary occlusion) decreased the myocardium ischemic alteration index (1.9 and 3.5 times, respectively) and the T-wave amplitude within 60 min after occlusion. Both effects were inhibited by Glibenclamide (Glib) and 5-HD. UMP and uridine decreased the number of premature ventricular beats 5.6 and 1.9 times and the duration of ventricular tachycardia 9.4 and 4.1 times, respectively. Glib and 5-HD inhibited the anti-arrhythmic parameters, 5-HD being less effective. Uridine and UMP decreased the duration of fibrillation 10.8 and 3.6 times, respectively, and this effect was not abolished by Glib and 5-HD. Thus, uridine and UMP, which are the precursors of UDP in the cell, possess cardioprotective properties. MitoKATP prevents mainly ischemic injuries and partially rhythm disorders.     

钾通道开放剂对离体兔心缺血再灌注损伤的保护作用

目的观察非选择性三磷酸腺苷敏感性钾(KATP)通道开放剂Pinacidil和线粒体型KATP(mitoKATP)通道开放剂Diazoxide预处理对高钾停跳离体兔心缺血再灌注损伤的保护作用,以及mitoKATP通道阻断剂5-hydroxydecanoic acid sodiumsalt(5HD)应用后其心肌保护作用的变化。方法采用离体兔心Langendorff灌注实验模型。离体兔心40只随机等分成5组(n=8):对照组(C组)、Pinacidil组(P组)、Diazoxide组(D组)、5HD Pinacidil组(HP组)和5HD Diazoxide组(HD组)。离体兔心用标准Thomas停搏液(4℃,K 16mmol/L)至心停跳,45min后再灌注20min,于心脏停跳前灌注药物15min,对比观察Pinacidil、Diazoxide及其与5HD合用时对再灌注后心功能及冠状动脉血流的影响以及再灌注末心肌超微结构、蛋白含量、脂质过氧化物丙二醛(MDA)以及腺苷酸含量的变化。结果再灌注后P组、D组、HP组心功能的恢复率均明显高于C组,心肌MDA的含量、蛋白的漏出量明显低于C组,超微结构观察损伤较轻;但HP组心功能的恢复要差于P组,心肌MDA的含量、蛋白的漏出量明显高于P组;HD组与C组各检测指标比较差异无统计学意义。结论Pinacidil(10μmol/L)和Diazoxide(30μmol/L)预处理对离体兔心缺血/再灌注心肌具有保护效果,且其保护效果可以部分被5HD所阻断,提示心肌mitoKATP通道可能是产生心肌保护作用的靶点之一。