人支气管上皮细胞5-脂氧合酶的表达与联苯胺的活化及细胞毒性

目的结合能肯定LOX介导联苯胺(BZDD)氧化的体外酶系统实验和人支气管上皮细胞(HBE)5-LOX蛋白表达与联苯胺对细胞DNA损伤关系的细胞实验研究,初步探讨细胞内5-LOX对外源化合物的代谢情况,为LOX作为细胞色素P450氧化代谢外源化合物的替代途径提供进一步的依据。结果在过氧化氢参与下,SLO可以协同氧化联苯胺,氧化后生成联苯胺二亚胺。SLO介导BZD氧化的Vmax值为1.42nmol/(min.nmol)SLO,BZD的Km值为1.48mmol/L。联苯胺可以使HBE细胞内5-LOX蛋白表达增加,AA861对5-LOX蛋白表达没有影响;联苯胺可以使HBE产生明显的DNA损伤,AA861可以明显抑制DNA损伤情况。结论在过氧化氢参与下,SLO可以介导联苯胺协同氧化。5-LOX在HBE细胞内的蛋白表达是可以经联苯胺调节的,特异性5-LOX抑制剂AA861对其蛋白表达无明显影响。HBE细胞内的5-LOX可能通过介导联苯胺协同氧化,产生亲电子自由基与DNA结合,使HBE细胞产生DNA损伤,AA861可以明显抑制该反应。     

天然黄酮类化合物对脂氧合酶介导吩噻嗪类等药物氧化的影响

目的研究天然黄酮类化合物茶多酚等对脂氧合酶(LOX)介导吩噻嗪类药物和异丙肾上腺素氧化反应的影响,探讨此类化合物抑制脂氧合酶协同氧化活性的可能机制。方法用分光光度法和电子自旋共振波谱仪(ESR)检测氧化反应的产物和自由基。结果大豆脂氧合酶(SLO)可介导吩噻嗪类药物氧化生成吩噻嗪阳离子自由基;天然黄酮类化合物茶多酚及其单体EGCG等可以抑制上述酶促氧化过程。SLO还可氧化异丙肾上腺素生成异丙肾上腺素红;棉子酚、DTT、GSH等酶活性调节物可抑制该氧化反应,而自由基清除剂BHA、BHT和天然黄酮类化合物茶多酚等对异丙肾上腺素红的生成没有影响。结论在本试验条件下,这些黄酮类化合物对SLO介导吩噻嗪类化合物氧化的抑制,可能主要是通过清除SLO介导外源性化学物氧化过程中产生的自由基发挥作用;此种对SLO协同氧化酶活力的抑制作用,在体内有可能减少或阻止能被LOX氧化活化产生自由基的外源化学物引起的致癌等毒作用。     

天然黄酮类抗氧化剂对脂氧合酶介导四种具有苯环结构化合物氧化的影响

目的　研究天然黄酮类抗氧化剂茶多酚(GTP)、表没食子儿茶素没食子酸酯 (EGCG)、槲皮素、芦丁对脂氧合酶介导愈创木酚、联苯胺、对苯二胺和二甲氧联苯胺协同氧化的影响 ,初步探讨此类抗氧化剂通过抑制脂氧合酶协同氧化作用的机制发挥其抗氧化作用的可能性。方法　用分光光度法和电子自旋共振技术 (ESR)检测加入或未加抗氧化剂等调节物的反应体系中反应产物及自由基中间产物的生成情况。结果　GTP ,EGCG ,槲皮素、芦丁均可降低大豆脂氧合酶 (SLO)介导的受试化合物协同氧化反应的速度 ,以及氧化产物和自由基中间产物的生成量。其对SLO介导愈创木酚氧化的半数抑制浓度 (IC50 )分别为 8.2mg·L- 1,17.4 ,4 1.4和 4 6 .1μmol·L- 1,均有显著意义地低于还原型谷胱甘肽、二硫苏糖醇、丁基羟基茴香醚、棉子酚。结论GTP ,EGCG ,槲皮素、芦丁均可明显抑制SLO介导愈创木酚、联苯胺等的氧化活化     

茶多酚对脂氧合酶介导酚噻嗪类与联苯胺等氧化相互作用的抑制

目的 研究茶多酚(GTP)及其单体表没食子儿茶素没食子酸酯(EGCG)对脂氧合酶(LOX)介导酚噻嗪类化合物与联苯胺(BZ)等相互作用的影响,探讨其通过抑制脂氧合酶介导这种氧化增强作用的新机制而发挥防癌和对抗化学物其他毒作用的可能性.方法 用分光光度法和电子自旋共振波谱仪(ESR)检测氧化产物和自由基.结果 大豆脂氧合酶(SLO)能介导酚噻嗪类对BZ等化学物氧化的增强作用.GTP、EGCG等对SLO介导的氧化增强效应均有抑制作用,其抑制能力有显著意义的高于LOX抑制剂棉子酚、还原剂二硫苏糖醇、谷胱甘肽、自由基清除剂丁羟基茴香醚和丁羟基甲苯.结论 SLO介导产生的酚噻嗪阳离子自由基可增强BZ等的氧化作用;GTP和EGCG可明显抑制此氧化增强效应.     

人足月胎盘脂氧合酶及其对外源化合物的代谢活性

脂氧合酶 (LOX)是一类非血红素铁蛋白。除对多不饱和脂肪酸 (PUFA)双加氧作用外 ,在PUFA或某些其他化合物参与下 ,其对外源化合物具有协同氧化酶活性。用吸附色谱法提取和纯化的人足月胎盘脂氧合酶 (HTPLO) ,能介导外源化合物的脱烷基、环氧化、磺化氧化等形式的协同氧化反应 ;同时 ,还能介导外源化合物之间的相互作用 ,增加它们的毒性或降低药物疗效。由于细胞色素P4 5 0和前列腺素合成酶在胎盘中含量很低甚至检测不到 ,因而 ,HTPLO被认为可能是包括致癌物活化在内的经胎盘毒物氧化代谢的重要途径。以往对LOX的研究绝大部分在体外非细胞系统进行 ,因而有必要加强在细胞内和体内的研究 ,更进一步探讨其协同氧化活性以及肯定在生物体内的这种作用。     

5-脂氧酶及其抑制剂在MPP~+诱导PC12细胞损伤中的作用

目的探究5-脂氧酶及其抑制剂在MPP~+诱导的PC12细胞损伤中的作用。方法以MPP~+诱导PC12细胞构建细胞损伤模型,以不同浓度的咖啡酸、齐留通预处理PC12细胞,光镜观察细胞形态变化,MTT法检测细胞活性,细胞免疫组化法测定5-脂氧酶的表达情况。结果成功建立MPP~+诱导得PC12细胞损伤模型。免疫组化结果显示,MPP~+1 mmol·L-1可激活细胞内5-脂氧酶蛋白,使其发生核膜移位。光镜和MTT结果表明,咖啡酸50μmol·L~(-1)和齐留通75μmol·L~(-1)可增加正常细胞数量,显著抑制MPP~+诱导的PC12细胞活性降低。此外,50μmol·L~(-1)咖啡酸可以抑制MPP~+诱导的5-LOX激活(抑制了核膜移位),但75μmol·L~(-1)齐留通对MPP~+诱导的5-LOX激活的无明显抑制作用。结论 5-脂氧酶抑制剂对MPP~+诱导的PC12细胞损伤有保护作用,5-LOX激活可能参与PD的发生。     

darbufelone对胃癌SGC-7901细胞增殖、凋亡的影响

目的观察环氧合酶-2/5-脂氧合酶双重抑制剂dar-bufelone对胃癌SGC-7901细胞生长的影响。方法MTT法测定darbufelone对胃癌SGC-7901细胞增殖的影响;TUNEL法检测细胞凋亡;RT-PCR法分析SGC-7901细胞中5-LOX和COX-2 mRNA的表达;免疫细胞化学法检测胃癌SGC-7901细胞中5-LOX和COX-2蛋白质的表达。结果dar-bufelone以时间剂量依赖的方式抑制SGC-7901细胞增殖;1.5×10-5、1.0×10-5和5×10-6mol.L-1darbufelone作用72 h后,细胞凋亡率分别为(30.3±2.1)%、(23.0±2.0)%和(15.0±1.5)%,均高于对照组(0.6±0.1)%(P<0.01);1.5×10-5、1.0×10-5和5×10-6mol.L-1darbufelone处理胃癌SGC-7901细胞72 h后,5-LOX和COX-2 mRNA及其蛋白质表达均减少(P<0.05)。结论环氧合酶-2/5-脂氧合酶双重抑制剂darbufelone对人胃癌SGC-7901细胞株有抑制增殖、诱导凋亡的作用。     

雷公藤内酯醇降调胰腺癌细胞5-脂氧合酶表达作用研究

目的探讨雷公藤内酯醇（TL）对胰腺癌细胞中5 脂氧合酶(5 LOX)蛋白表达及胰腺癌细胞凋亡的影响。方法应用RT PCR法和免疫细胞化学法检测胰腺癌细胞株SW1990中5 LOX表达，同时应用流式细胞术检测胰腺癌细胞SW1990的凋亡指数。结果胰腺癌细胞株SW1990表达5 LOX，正常胰腺组织不表达； TL可抑制SW1990中5 LOX表达，并促进胰腺癌细胞SW1990凋亡，作用随浓度的增加而增强(P＜0.01)；细胞凋亡与5 LOX蛋白的表达相关(P＜0.01)。结论TL可抑制胰腺癌细胞SW1990中5 LOX的表达，并促进胰腺癌细胞凋亡     

5-脂氧合酶和结直肠癌关系的研究进展

结直肠癌是我国最常见的胃肠道恶性肿瘤之一,发病率仅次于食管癌和胃癌,且发病率和病死率呈逐年升高趋势.花生四烯酸代谢通路在肿瘤的发生发展中起着重要作用.环氧合酶(cyclooxygenase,COX)及脂氧合酶(lipoxygenase,LOX)是催化体内花生四烯酸代谢通路的两个关键酶,花生四烯酸可通过环氧合酶(COX)通路代谢,主要生成血栓素A2(TXA2)、前列环素(PGI2)、前列腺素E2(PGE2)、前列腺素D2(PGD2)、前列腺素F2α(PGF2α),参与多种疾病的发生;亦可通过脂氧合酶(LOX)途径生成具有生物活性的多种物质,如炎症介质HD4等.大量实验证明,脂氧合酶代谢途径中的代谢产物在肿瘤中表达升高,其表达水平与肿瘤的分期、分级、转移、预后生存相关,其代谢途径通过影响细胞的增殖、凋亡、血管生成、细胞的侵袭和迁移等机制参与肿瘤的发生发展.使用脂氧合酶抑制剂(lipoxygenase inhibitors)特别是5-脂氧合酶抑制剂(5-lipoxygenase inhibitors)可预防及抑制肿瘤的发生、发展.     

咖啡酸对氧化应激诱导的PC12细胞5-脂氧酶激活的抑制作用

目的探讨咖啡酸是否通过抑制氧化应激诱导的5-脂氧酶(5-LOX)激活而减轻细胞损伤。方法稳定转染绿荧光蛋白(GFP)-5-LOX的PC12细胞,预先给予咖啡酸0.001~10μmol.L-1和对照药MK886,30min后观察缺氧缺糖/恢复(OGD/R)及过氧化氢(H2O2)160μmol.L-1处理后的变化。MTT法和碘化丙啶染色法分析细胞存活率和死亡率;荧光显微镜观察OGD 2 h/R2 h和H2O2处理40 min时5-LOX的核膜移位;ELISA法测定OGD 2 h/R 3 h时5-LOX代谢产物的生成;DCF法检测OGD 2 h/R 0.5 h细胞内活性氧(ROS)的产生。结果 OGD 2 h/R 24 h GFP-5-LOX转染和GFP-转染PC12细胞的存活率分别为(63.1±6.6)%和(70.7±6.9)%;H2O2处理24 h细胞存活率分别为(62.5±7.7)%和(75.7±9.5)%。在GFP-5-LOX转染的PC12细胞中,咖啡酸和对照药MK886可使OGD/R细胞存活率从(63.1±6.6)%分别增加到(87.3±2.0)%和(89.9±6.3)%,细胞坏死率从(31.4±1.5)%降低到(10.1±2.0)%和(11.7±1.3)%(P<0.01);使H2O2处理细胞存活率从(62.51±7.65)%增加到(92.59±4.02)%和(75.31±6.60)%;使OGD/R细胞CysLTs的生成从261.1±33.7降低到108.5±16.7和(90.6±19.5)ng.g-1蛋白(P<0.01)。此外,咖啡酸抑制OGD/R诱导PC12细胞的ROS产生,IC50值为8.021μmol.L-1;抑制OGD/R诱导的GFP-5-LOX转染的PC12细胞5-LOX核膜移位,IC50值为0.974μmol.L-1;抑制H2O2诱导的GFP-5-LOX转染的PC12细胞5-LOX核膜移位,IC50值为0.501μmol.L-1;MK886无上述作用。结论咖啡酸可抑制氧化应激诱导的PC12细胞5-LOX激活,对缺血损伤的PC12细胞具有保护作用。     

Spinal administration of lipoxygenase inhibitors suppresses behavioural and neurochemical manifestations of naloxone-precipitated opioid withdrawal

1. This study investigated the role of spinal lipoxygenase (LOX) products in the induction and expression of opioid physical dependence using behavioural assessment of withdrawal and immunostaining for CGRP and Fos protein expression in the spinal cord. 2. Administration of escalating doses (5-50 mg kg-1; i.p.) of morphine for 5 days markedly elevated CGRP-like immunoreactivity in the dorsal horn of the rat spinal cord. Naloxone (2 mg kg-1; i.p.) challenge precipitated a robust withdrawal syndrome that depleted CGRP-like immunoreactivity and increased the number of Fos-like immunoreactive neurons in the dorsal horn. 3. Intrathecal administration of NDGA (10, 20 microg), a nonselective LOX inhibitor, AA-861 (1.5, 3 microg), a 5-LOX selective inhibitor, or baicalein (1.4, 2.8 microg), a 12-LOX selective inhibitor, concurrently with systemic morphine for 5 days or as a single injection immediately preceding naloxone challenge, blocked the depletion of CGRP-like immunoreactivity, prevented increase in the number of Fos-like immunoreactive neurons in the dorsal horn, and significantly attenuated the morphine withdrawal syndrome. 4. The results of this study suggest that activity of LOX products, at the spinal level, contributes to the expression of opioid physical dependence, and that this activity may be expressed through increased sensory neuropeptide release.     

Evaluation of the antioxidative properties of lipoxygenase inhibitors

BackgroundOxidative stress is a component of many pathological conditions including neurodegenerative diseases and inflammation. An important source of reactive oxygen species (ROS) are lipoxygenases (LOX) – enzymes responsible for the metabolism of arachidonic acid and other polyunsaturated fatty acids. LOX inhibitors have a protective effect in inflammatory diseases and in neurodegenerative disorders because of their anti-inflammatory activity. However, the molecular mechanism of the protective action of LOX inhibitors has not yet been fully elucidated.MethodsThe aim of this study was to compare the antioxidative potential of widely used LOX inhibitors: BWB70C, AA-861, zileuton, baicalein and NDGA. The antioxidative properties were evaluated in cell-free systems. We measured the effect of the tested compounds on iron/ascorbate-induced lipid peroxidation and on carbonyl group formation in the rat brain homogenate. Direct free radical scavenging was analyzed by using DPPH assay.ResultsOur data showed that the inhibitor of all LOXs, i.e., NDGA, 5-LOX inhibitor BWB70C and the inhibitor of 12/15-LOX, baicalein, significantly decreased the level of lipid and protein oxidation. The free radical scavenging activity of these inhibitors was comparable to known ROS scavengers, i.e., resveratrol and trolox. Zileuton (the inhibitor of 5-LOX) slightly prevented lipid and protein oxidation, it also scavenged the DPPH radical. AA-861 (the inhibitor of 5 and 12/15-LOX) slightly protected lipids against Fe/asc-evoked lipid peroxidation at high concentrations, but had no effect on carbonyl group formation and DPPH scavenging.ConclusionsOur results indicate that some LOX inhibitors demonstrate potent anti-oxidative, free radical scavenging properties. AA-861, whose antioxidative potential is very weak, may be a specific tool to be used in experimental and perhaps even clinical applications.     

Dexmedetomidine‐induced contraction involves c‐Jun NH2‐terminal kinase phosphorylation through activation of the 5‐lipoxygenase pathway in the isolated endothelium‐denuded rat aorta

Vasoconstriction induced by dexmedetomidine, a highly selective alpha‐2 adrenoceptor agonist, mainly involves c‐Jun NH₂‐terminal kinase (JNK) phosphorylation in the isolated endothelium‐denuded aorta. We carried out an in vitro study to determine the main arachidonic acid metabolic pathway that is involved in dexmedetomidine‐induced JNK activation. Cumulative dexmedetomidine concentration‐contractile response curves were generated in the endothelium‐denuded rat aorta in the presence or absence of the following inhibitors: the JNK inhibitor SP600125, the phospholipase A₂ inhibitor quinacrine dihydrochloride, the non‐specific lipoxygenase (LOX) inhibitor nordihydroguaiaretic acid, the 5‐LOX inhibitor AA‐861, the dual 5‐LOX and cyclooxygenase (COX) inhibitor phenidone, the non‐specific COX inhibitor indomethacin, the cytochrome p450 epoxygenase inhibitor fluconazole, the COX‐1 inhibitor SC‐560, and the COX‐2 inhibitor NS‐398. The effect of the alpha‐2 adrenoceptor inhibitor rauwolscine and other inhibitors, such as quinacrine dihydrochloride, nordihydroguaiaretic acid, AA‐861, phenidone, indomethacin and the protein kinase C inhibitor GF 109203X, on dexmedetomidine‐induced JNK phosphorylation was investigated in rat aortic vascular smooth muscle cells with western blotting. The effect of dexmedetomidine on 5‐LOX and COX‐2 expression was investigated in vascular smooth muscle cells. SP600125, quinacrine dihydrochloride, nordihydroguaiaretic acid, AA‐861, phenidone, rauwolscine and chelerythrine attenuated dexmedetomidine‐induced contraction. Indomethacin slightly attenuated dexmedetomidine‐induced contraction. Fluconazole and SC‐560 had no effect on dexmedetomidine‐induced contraction, whereas NS‐398 attenuated contraction. SP600125, rauwolscine, quinacrine dihydrochloride, nordihydroguaiaretic acid, AA‐861, phenidone and GF 109203X attenuated dexmedetomidine‐induced JNK phosphorylation. 5‐LOX and COX‐2 were upregulated by dexmedetomidine. Thus, dexmedetomidine‐induced alpha‐2 adrenoceptor‐mediated contraction is mediated mainly by 5‐LOX and partially by COX‐2, which leads to JNK phosphorylation.     

菲啰啉对不同氧化剂和多柔比星所致CHL细胞DNA链断裂的影响

目的 为了研究菲啰啉对2种氧化剂和抗癌药多柔比星诱发细胞DNA损伤的影响, 并初步探讨其损伤机制。方法 用不同浓度菲啰啉预处理CHL细胞30 min, 再分别加入3种不同染毒受试物,共同培养一定时间(0.3 mmol·L^-1重铬酸钾：105 min； 0.5 μmol·L^-1多柔比星：5 min； 0.4 mmol·L^-1过氧化氢(H₂O₂)：25 min)后, 用碱性单细胞凝胶电泳方法(ASCGE)测定DNA链断裂情况, 并同时以菲啰啉与二甲亚砜(DMSO，0.33 mol·L^-1)比较对H₂O₂致DNA损伤中·OH的产生和清除。结果 3种染毒受试物均可明显引起CHL细胞DNA链断裂；而当3 μmol·L^-1菲啰啉预处理后, 可使重铬酸钾、H₂O₂所致DNA迁移长度和细胞拖尾率明显降低, 并超过DMSO降低H₂O₂的损伤作用, 当菲啰林浓度升至12 μmol·L^-1时, 可完全消除这两种因素所致的DNA链断裂损伤；10 μmol·L^-1菲啰啉可抑制多柔比星所致DNA损伤, 但浓度直至60 μmol·L^-1仍不能完全消除多柔比星的损伤作用。结论 菲啰啉对2种氧化剂和多柔比星所致DNA损伤均有不同程度的防护作用,同时提示重铬酸钾和H₂O₂所致的DNA损伤主要与需过渡金属离子参与的·OH产生有关, 而多柔比星所致损伤仅部分与此有关。     

穿心莲内酯对人肺腺癌A549细胞NF-κB通路的调控作用

目的探讨穿心莲内酯对肿瘤细胞生长的作用及机制。方法人肺腺癌A549细胞分别与穿心莲内酯1.5～30μmol·L-1作用24h,以及穿心莲内酯30μmol·L-1作用4～24h。用MTT法检测A549细胞存活率;Western印迹法检测在肿瘤坏死因子α(TNF-α)10μg·L-1刺激下,穿心莲内酯30μmol·L-1对NF-κB信号通路中的相关蛋白NF-κB抑制因子α(IκBα)、磷酸化IκBα、IκB激酶β(IKKβ)和磷酸化IKKβ表达的影响;ELISA法检测穿心莲内酯对A549细胞核内NF-κBDNA结合活性的影响。结果穿心莲内酯的浓度和作用时间与A549细胞的存活率密切相关,穿心莲内酯30μmo·lL-1作用24h,A549细胞的存活率下降到(22.0±1.2)%,而穿心莲内酯1.5μmol·L-1作用24h或者穿心莲内酯30μmol·L-1作用4h对A549细胞的存活率几乎无影响。Western印迹法显示,穿心莲内酯能够抑制TNF-α诱导的NF-κB信号通路中IKKβ的磷酸化,抑制IκBα的磷酸化,推迟IκBα的降解,对IKKβ的表达无影响。穿心莲内酯还能够抑制TNF-α诱导的A549细胞核内NF-κBp65蛋白的DNA结合活性,抑制率达32%。结论穿心莲内酯通过影响NF-κB信号通路抑制A549细胞的生长。     

Co-oxidation-mediated xenobiotic activation and cytotoxicity by 12-lipoxygenase in intact platelets

Peroxidase-mediated co-oxidation process has been suggested as a major alternative pathway for xenobiotic bioactivation other than hepatic cytochrome P450 monooxygenase system. Despite the wealth of reports on the possible involvement of co-oxidation in bioactivation of various compounds, clear manifestation of co-oxidation-mediated xenobiotic bioactivation in intact cell system without extra sources of peroxidase system has been difficult to demonstrate, mainly due to the natural scarcity of peroxidase activities in fresh intact cells. In the present study, arachidonic acid (AA) dependent bioactivation of alpha-naphthol, a representative phenolic compound, was demonstrated as shown by covalent binding increases in alpha-naphthol concentration dependent manner in freshly prepared intact platelets, where two AA dependent representative peroxidases, 12-lipoxygenase (12-LOX) and prostaglandin H synthase (PHS) are abundantly expressed. Inhibitors of 12-LOX attenuated the covalent binding of alpha-naphthol while inhibitors of PHS were not effective, indicating the predominant role of 12-LOX in AA-initiated co-oxidation in intact platelets. In addition, free radical scavengers and thiol donors prevented effectively the bioactivation of alpha-naphthol, suggesting the involvement of naphthoxy radical or naphthoxy-derived radical generation. Notably, the co-oxidation process resulted in enhanced cytotoxicities of alpha-naphthol against platelets indeed, as observed by cellular membrane disturbance and mitochondrial membrane potential decrease. With these results, we believe that an important in vitro evidence of peroxidase-mediated xenobiotic activation was provided for understanding the toxicological implication of peroxidase-mediated co-oxidation in the xenobiotic bioactivation.     

ATP敏感性钾通道在U50488H抑制去氧肾上腺素诱导的乳大鼠心肌细胞肥大中的作用

目的研究ATP敏感性钾通道(KATP)在κ-阿片受体激动剂U50488H抑制乳大鼠心肌细胞肥大中的作用。方法以原代培养的新生大鼠心肌细胞为模型,应用去氧肾上腺素(PE)10μmol.L-1诱导心肌细胞肥大。细胞处理分为正常对照组、PE10μmol.L-1模型组、5-羟基癸酸(5-HD)100μmol.L-1组,格列本脲(Gli)50μmol.L-1组、PE10μmol.L-1+U50488H1μmol.L-1组、PE10μmol.L-1+Gli50μmo.lL-1+U50488H1μmo.lL-1组和PE10μmo.lL-1+5-HD100μmo.lL-1+U50488H1μmol.L-1组,细胞培养液中先加入Gli50μmol.L-1或者5-HD100μmol.L-1,30min后再加入U50448H1μmol.L-1,30min后最后加入PE10μmol.L-1,48h后进行指标检测,Lowry等法检测心肌细胞蛋白质含量;消化分离法及计算机图像分析系统检测心肌细胞体积;Western印迹法测定KATP通道Kir6.2亚基的表达。结果与正常对照组相比,PE10μmol.L-1模型组使心肌细胞总蛋白质含量比正常细胞增加了52.2%,细胞体积增加了95.0%,而Kir6.2的表达没有明显变化。与PE10μmol.L-1模型组相比,细胞加入U50488H1μmol.L-1后,心肌细胞总蛋白质含量和细胞体积分别降低了42.3%和47.9%,但是Kir6.2表达增加了39.2%。与PE10μmo.lL-1+U50488H1μmol.L-1组相比,在非选择性KATP通道阻滞剂Gli50μmol.L-1或线粒体KATP通道阻滞剂5-HD100μmol.L-1存在的情况下,Kir6.2表达分别减少了49.3%和52.1%,U50488H抑制PE诱导的心肌细胞肥大作用减弱,并且两组之间没有显著差异。结论 U50488H可能是通过开放KATP通道,主要是线粒体KATP通道来抑制PE诱导的乳大鼠心肌细胞肥大。