共查询到19条相似文献,搜索用时 78 毫秒
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目的 分析间歇性缺氧对人绒毛膜滋养层细胞(HTR8/SVneo)内质网应激及凋亡的影响,并探讨其可能的机制。方法 选用人绒毛膜滋养层细胞(HTR8/SVneo),间歇性缺氧-24 h组和间歇性缺氧-48 h组分别进行24 h和48 h的间歇性缺氧处理,空白对照组始终置于常氧中培养。观察间歇性缺氧对细胞凋亡与增殖,以及内质网应激相关分子、细胞凋亡相关蛋白、细胞周期相关蛋白和缺氧诱导因子-1α(HIF-1α)表达的影响。结果 与空白对照组比较,间歇性缺氧组CCAAT/增强子结合蛋白同源蛋白(CHOP)、葡萄糖调节蛋白78(GRP78)、激活转录因子6(ATF6)、X-盒结合蛋白1(XBP-1)mRNA和蛋白表达水平显著增加,早期凋亡率显著增加,Caspase-3蛋白、多聚ADP-核糖聚合酶(PARP)mRNA和蛋白表达水平显著增加,HIF-1αmRNA和蛋白表达水平显著增加,并随缺氧时间延长而增加(P<0.05);与空白对照组比较,间歇性缺氧可显著抑制HTR8/SVneo细胞增殖,并随缺氧时间延长而细胞活力降低(P<0.05);与空白对照组比较,间歇性缺氧组细胞周期蛋白D1(C... 相似文献
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缺氧诱导因子(HIF)是缺氧环境下介导细胞适应性反应最主要的转录因子,内质网应激(ERS)是应激状态下(包括缺氧在内)恢复细胞内蛋白质稳态的重要细胞反应。HIF和ERS之间存在密切的相互作用:ERS不仅直接调节HIF的合成和活性,还对HIF靶基因的表达(如促红细胞生成素和血管内皮生成因子)有调节作用;HIF也可以调节ERS。本研究综述HIF的特点和调节机制、ERS相关的未折叠蛋白质反应和凋亡,以及HIF和ERS间相互作用的研究,为进一步研究提供理论依据。 相似文献
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目的 通过动物实验及体外实验探索饮酒是否促进乳腺癌恶性进展,且这一作用是否与其诱导的慢性应激有关。方法 利用小鼠乳腺癌移植瘤模型,体内观察2%乙醇慢性处理的小鼠乳腺癌E0771细胞对体内细胞生长转移的影响;利用体外细胞学实验观察0.2%乙醇慢性诱导对小鼠乳腺癌细胞E0771增殖、迁移及非锚定生长能力的影响;同时用分子生物学方法探索细胞内ROS水平及慢性内质网应激蛋白如p-eIF2a、Bip、XBP1-s等蛋白表达水平是否发生改变。结果 与对照组相比,饮酒组小鼠体内肿瘤生长速度加快,转移增加;体外酒精处理可以显著促进乳腺癌细胞增殖、迁移等恶性生物学行为,酒精慢性处理可以诱导ROS、内质网应激活化蛋白p-eIF2a、Bip、XBP1-s表达上升。结论 饮酒可能通过诱导乳腺癌细胞内质网应激促进其恶性进展。 相似文献
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目的:通过慢性间歇性缺氧(CIH)合并脑缺血再灌注(CIR)大鼠模型的建立,研究睡眠呼吸暂停综合征(OSAS)对脑梗塞的影响。方法:2月龄Sprague-Dewley(SD)大鼠34只,随机选取10只在缺氧箱中行血氧检测,余随机分成4组:空白对照组(UC,n=6),假手术组(n=6),CIR组(n=6),CIH+CIR组(n=6)。CIH+CIR组大鼠每天间歇性缺氧8小时。UC组、假手术组及CIR组暂不作处理。8周后CIR组和CIH+CIR组均用线栓法制备大脑中动脉缺血(MCA0)模型。通过神经功能缺损评分观察大鼠大体情况;2,3,5-氯化三苯基四氮唑(TTC)染色观察脑梗死体积。结果:CIH+CIR组与CIR组梗死体积和神经功能评分均有明显的差异。结论:本实验建立的慢性间歇性缺氧合并脑缺血再灌注大鼠模型可满足OSAS+脑梗死基础研究的需要,CIH可加重脑缺血再灌注损伤。 相似文献
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目的:探究牛磺熊去氧胆酸钠(tauroursodeoxycholic acid sodium,TUDCA)在间歇性低氧(intermittent hypoxia,IH)模型小鼠肺组织中抑制细胞凋亡的机制。方法:32只C57小鼠随机分为对照组、TUDCA组、IH组和IH+TUDCA组,每组8只。将C57小鼠放入低氧舱中进行IH处理4周 (氧气浓度从21%下降到10%,再从10%恢复到21%为一个循环,每个循环的时间为90s),每天持续8h。4周IH处理后,Western印迹检测caspase-12和cleaved caspase-3在肺组织中的表达。同时,Western印迹、免疫组织化学和实时定量PCR检测葡萄糖调节蛋白78(glucose regulated protein 78,GRP78) 和CCAAT/增强结合蛋白同源蛋白(CCAAT/enhancer-binding protein homologous protein,CHOP)的表达。结果:与对照组和TUDCA组相比,IH组小鼠肺组织中caspase-12,cleaved caspase-3,GRP78和CHOP表达明显升高(均P<0.01);而在IH+TUDCA组中,TUDCA能够显著地减少上述蛋白的表达(均P<0.05)。结论:慢性的IH能够导致肺组织中内质网应激介导的细胞凋亡,而TUDCA可以通过抑制内质网应激的激活来降低细胞的凋亡水平。 相似文献
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慢性肾病患者肾小管上皮细胞内质网应激与细胞凋亡的关系 总被引:5,自引:2,他引:3
目的 探讨慢性肾病(chronic kidney disease,CKD)患者蛋白尿诱导肾小管上皮细胞内质网应激与细胞凋亡的关系.方法 应用免疫组织化学技术检测CKD患者肾小管上皮细胞中内质网应激标志蛋白氧调节蛋白150(cells-oxygen-regulated protein150, ORP150)和糖调节蛋白78(glucose-regulated protein 78, GRP78)的表达;TUNEL法检测细胞凋亡.对各指标与CKD患者24 h尿蛋白量进行相关性分析.结果 CKD患者肾小管上皮细胞细胞质中ORP150、GRP78的表达较正常对照组显著增强(P<0.01),且轻、中、重度蛋白尿3组各组间亦均有显著性差异(P<0.01),并与尿蛋白水平呈正相关(r=0.695,r=0.76,P<0.01);各组小管上皮细胞凋亡系数(apoptosis index,AI)均亦有显著性差异(P<0.01),并与尿蛋白水平呈正相关性(r=0.835,P<0.01).结论 CKD患者肾小管上皮细胞有内质网应激与凋亡的发生,并且其强度与蛋白尿水平呈正相关关系.内质网应激可能是大量蛋白尿引起小管上皮细胞凋亡的重要环节. 相似文献
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目的:体外构建肿瘤细胞缺糖缺氧( OGD)模型,观察缺糖缺氧应激条件对肿瘤细胞凋亡的影响及其机制。方法:利用平衡盐溶液EBSS取代细胞正常培养液构建缺糖模型,利用连二亚硫酸钠消耗培养基中氧构建缺氧模型;实验分为对照组、缺糖缺氧4、8和12 h组。MTT法检测各组细胞增殖率;Western blotting检测各组Hel... 相似文献
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目的:通过大鼠造模,探讨慢性间歇性缺氧(chronic intermittent hypoxia,CIH)状态下,大鼠舌下神经元超微结构损伤的情况。方法:将12只雄性 SD大鼠(8 周龄,体重 180~200 g)随机均分为 CIH 组和常氧对照组,每组各6只。CIH组6只大鼠饲养于氧浓度5%~21%之间循环的低氧舱中,每天8 h,持续35 d;对照组大鼠饲养箱的氧浓度保持在21%,持续35 d。5周后在电镜下观察两组大鼠舌下神经元超微结构损伤的情况。结果:电镜结果显示常氧组大鼠舌下神经元细胞膜完整,核膜平滑,染色质均匀,细胞器丰富。而CIH组细胞膜呈不连续性;细胞核膜内陷,胞核呈不规则形;神经元内出现水肿空泡化;线粒体肿胀,外膜模糊不清,有破损情况;高尔基体和滑面内质网出现肿胀扩张现象;还可见脂褐素。结论:慢性间歇性缺氧可诱导大鼠舌下神经核损伤,可在电镜下观察到舌下神经核一系列超微结构变化。 相似文献
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内质网是一种负责蛋白质合成、折叠以及转运,脂类生物合成,空泡运输以及胞内钙存储的多功能细胞器。内质网腔内未折叠蛋白质的蓄积及钙离子稳态的打破,诱发内质网应激,发生具有保护性的未折叠蛋白反应。内质网应激与多个信号通路相互联系,参与炎症、凋亡的发生发展,近年来得到越来越多的关注。本文就内质网应激发生机制及相关的眼科疾病的研究进展作一综述。 相似文献
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姜黄素对内质网应激诱导小鼠肝损伤的保护作用 总被引:1,自引:0,他引:1
目的 探讨姜黄素对内质网应激(ERS)诱导小鼠急性肝损伤的保护作用.方法 建立衣霉素诱导ERS的肝损伤模型,测定肝损伤小鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)水平、肝匀浆中还原型谷胱甘肽(GSH)、丙二醛(MDA)和超氧化物歧化酶(SOD)含量及肝指数.实时荧光定量PCR法检测小鼠肝组织中葡萄糖调节蛋白78(GRP78/Bip) mRNA表达及半定量免疫组化法检测肝组织GRP78/Bip蛋白水平,并行肝组织病理学检查.结果 姜黄素能降低衣霉素诱导ERS肝损伤小鼠血清中ALT、AST水平和肝组织匀浆中MDA含量;提高肝组织匀浆中SOD、GSH活性;同时姜黄素能明显抑制肝组织中GRP78/Bip mRNA和蛋白的表达.HE染色结果显示姜黄素能明显改善模型组小鼠肝脏组织病变范围与程度,使炎细胞浸润减少.结论 姜黄素可能通过抗氧化作用对ERS诱导的肝损伤小鼠发挥保护作用. 相似文献
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目的:探讨内质网应激在四氯化碳(CCl4)诱导的小鼠急性肝损伤中的变化及作用机制。方法C57BL/6小鼠30只,随机分为模型组和对照组各15只,模型组给予20% CCl4(0.1 mL/10 g)腹腔注射制备小鼠急性肝损伤模型,对照组给予橄榄油溶液腹腔注射(0.1 mL/10 g)作为正常对照。采用病理染色观察小鼠肝组织病理形态学和肝细胞内质网应激相关蛋白以及凋亡蛋白的表达情况,采用蛋白质印迹法测定小鼠肝脏内质网应激相关蛋白以及凋亡相关蛋白的表达变化趋势。结果CCl4腹腔注射后8 h,模型组小鼠肝脏出现明显的损伤,肝组织 GRP78蛋白以及 cleaved caspase -12表达量显著升高(P <0.05),cleaved caspase -3表达量亦显著升高(P <0.05);TUNEL 法检测结果均显示模型组肝脏有严重损伤,大量肝细胞发生凋亡,凋亡指数较对照组明显升高(P <0.05),而 PCNA 染色显示模型组肝细胞增殖指数明显少于对照组(P <0.05);相蛋白质印迹显示,模型组内质网应激相关蛋白以及凋亡蛋白表达量均明显升高,同时伴有线粒体细胞色素 c 的释放,而促细胞增殖蛋白p -Akt、PCNA 表达量明显降低。结论内质网应激反应介导的线粒体细胞凋亡通路参与了 CCl4诱导的小鼠急性肝损伤的发病过程。 相似文献
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目的: 初步观察内质网应激在氟中毒大鼠肾组织中的变化,探索内质网应激在氟中毒肾损伤机制中的作用。方法: 48只Wistar 大鼠按体重平均分成4组:常食对照组、常食加氟组、低钙对照组和低钙加氟组;分别给予常食和低钙饮食,加氟组大鼠饮水中投氟化钠(NaF)(221 mg•L-1)3个月。实验结束后,取一侧肾脏制作病理切片,在光镜下观察形态学变化。取各组大鼠50 mg肾组织抽提总RNA,利用RT-PCR技术分析内质网应激相关基因Grp78、Xbp1、CHOP和PDI的表达水平。结果:光镜下可见,常食加氟组大鼠肾组织以近端小管和远端小管上皮细胞水肿和空泡变性为主;低钙加氟组大鼠肾组织近端小管和远端小管上皮细胞呈现水肿和空泡变性,伴有散在的坏死、轻度再生修复和肾间质充血;常食对照组和低钙对照组大鼠肾组织无明显变化。RT-PCR产物经半定量分析显示,低钙加氟组和常食加氟组大鼠肾组织Xbp1的表达较相应对照组明显增强(P<0.05),低钙加氟组大鼠肾组织Grp78 mRNA表达较常食加氟组和低钙对照组明显增强(P<0.05或 P<0.01);而低钙加氟组大鼠肾组织PDI的表达较常食加氟组明显下降(P<0.05)。各组大鼠肾组织CHOP表达差异无显著性(P>0.05)。结论:过量氟可造成肾组织损伤,低钙营养进一步加剧了氟对肾的损伤作用,而内质网应激很可能参与该损伤机制。 相似文献
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Hydrogen sulfide regulates vascular endoplasmic reticulum stress in apolipoprotein E knockout mice 总被引:1,自引:0,他引:1
Background Atherosclerosis is an important cardiovascular disease, becoming a major and increasing health problem in developed countries. However, the possible underlying mechanisms were not completely clear. In 2009, our research group first discovered that hydrogen sulfide (H2S) as a novel gastrotransmitter played an important anti-atherosclerotic role. The study was designed to examine the regulatory effect of hydrogen sulfide (H2S) on endoplasmic reticulum stress (ERS) in apolipoprotein E knockout (apoE-/-) mice fed a Western type diet.
Methods C57BL/6 mice and homozygous apoE-/- mice were fed a Western type diet. C57BL/6 mice were injected intraperitoneally with normal saline (5 ml/kg per day) as control group. The apoE-/- mice were treated with the same dose of normal saline as the apoE-/- group, injected intraperitoneally with sodium hydrosulfide (NaHS, an H2S donor, 56 μmol/kg per day) as the apoE-/-+NaHS group and injected intraperitoneally with DL-propargylglycine (PPG, a cystathionine-γ-lyase inhibitor, 50 mg/kg, per day) as the apoE-/- +PPG group. After 10 weeks, the mice were sacrificed and the plasma lipids were detected. Sections of aortic root from these animals were examined for atherosclerotic lesions by HE and oil red O staining. The aortic ultrastructure and microstructure were analyzed with the help of light and electronic microscope. Glucose-regulated protein 78 (GRP78), caspase-12, copper-andzinc-containing superoxide dismutase (Cu/ZnSOD) and Mn-containing superoxide dismutase (MnSOD) protein expression in aortic tissues were detected with immunohistochemistry. The level of intracellular reactive oxygen species (ROS) were measured by using a commercial assay kit.
Results Compared with control mice, apoE-/- mice showed increased plasma levels of total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL), decreased high density lipoprotein (HDL), increased aortic plaque size, destroyed ultra-structure of aortic tissue, and increased expression of GRP78 and caspase-12 proteins. Compared with apoE-/- mice, H2S donor-treated apoE-/- mice showed a decreased plasma LDL level, lessened plaque necrosis and attenuated aortic ultra-structural disorder. H2S donor-treatment induced GRP78 expression but suppressed caspase-12 expression in aortic lesions. However, compared with apoE-/- mice, PPG treated apoE-/- mice showed enlarged plaque size, more severe ultrastructural disorder of the aortic tissue and reduced GRP78 staining in aortic lesions. The plasma lipids and the staining of caspase-12 in apoE-/- + PPG rats did not significantly differ from those in the apoE-/-mice. Consistently, H2S induced SOD expression, accompanied by a reduced level of ROS.
Conclusion H2S plays a regulatory role in aortic ERS and reduces atherosclerotic lesions in apoE-/- mice fed with a Western type diet.
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The effect of oxidative stress in myocardial cell injury in mice exposed to chronic intermittent hypoxia 总被引:7,自引:0,他引:7
LIU Jian-nan ZHANG Jie-xin LIU gan QIU Yan YANG Di YIN Guo-yong ZHANG Xi-long 《中华医学杂志(英文版)》2010,123(1):74-78
Background Obstructive sleep apnea syndrome (OSAS) is an important risk factor for cardiovascular diseases. Chronic intermittent hypoxia (CIH) is considered to be one of the most important causes of cardiovascular diseases in OSA patients. This repeated hypoxia and reoxygenation cycle is similar to hypoxia-reperfusion injury, which initiates oxidative stress. In this study, we observed cardiocytes injury induced by CIH and the effect of N-acetylcysteine (NAC). Methods Thirty ICR mice were randomly assigned to 3 groups: control, CIH and NAC (CIH+NAC) groups. Malondialdehyde (MDA) and superoxide dismutase (SOD) of cardiocyte homogenates were measured. Serum lipids were measured by an instrument method. Serum cardiac troponin I (cTnl) was detected by enzyme-linked immunosorbent assays (ELISA). Myocardium pathological sections were observed. Results (1) The SOD activity and MDA concentration of cardiocyte homogenates in the CIH group were significantly higher than in other groups (P 〈0.005). The MDA concentration of the NAC group was lower than that of the control group (P 〈0.01). (2) The serum cTnl concentration of the CIH and NAC groups was significantly higher than that of the control group (P 〈0.01). (3) Serum triglyceride levels in the NAC group were lower than in the other groups (P 〈0.01), while there were no significant differences in low density lipoprotein and high density lipoprotein among the three groups. (4) The degeneration of myocardium, transverse striation blurred, and fabric effusion were observed in tissue sections in the CIH and NAC groups. However, normal tissue was found in the control group. Conclusion The oxidative stress induced by CIH can injure cardiocytes and the injury effect can be partially inhibited by NAC. 相似文献
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目的:Sigma-1受体分子伴侣(Sigma-1 receptor chaperone,Sig-1R)是内质网中主要的伴侣蛋白,参与细胞凋亡等生物学行为,是多种疾病的治疗靶点?本研究旨在探讨Sig-1R基因表达抑制对内质网应激和足细胞损伤的影响,为Sig-1R及内质网应激在肾损伤中的作用提供新视点?方法:体外培养永生性小鼠足细胞系(MPC5),采用LipofectamineTM 2000与Sig-1R siRNA结合形成Sig-1R siRNA-脂质体复合物瞬时转染足细胞,设正常组?阴性对照组和Sig-1R干扰组?采用real-time PCR和Western blot检测Sig-1R的表达水平;Hochest染色法观察凋亡的足细胞核,计数凋亡率;采用Western blot 检测足细胞nephrin?desmin?凋亡相关因子bcl-2?bax?caspase 3,8,9,12的表达水平?结果:①与对照组相比,干扰组Sig-1R核酸和蛋白表达均明显下降(P < 0.05);②与对照组相比,干扰组足细胞裂孔隔膜蛋白nephrin表达显著下降,肌间蛋白desmin表达显著上升(P < 0.05);③与对照组相比,干扰组中凋亡的足细胞数显著增加,抗凋亡蛋白Bcl-2表达明显下降,促凋亡蛋白bax表达明显增加,bcl-2/bax<1∶2(P < 0.05),凋亡级联反应执行蛋白caspase-3明显活化(P < 0.05);④干扰组中,内质网和线粒体途径相关凋亡蛋白caspase-12,9明显活化(P < 0.05),而死亡受体相关凋亡蛋白caspase-8未见明显活化?结论:Sig-1R基因表达抑制可通过诱导内质网应激介导的足细胞凋亡,引起足细胞损伤,提示内质网应激部分参与Sig-1R诱导的足细胞损伤? 相似文献