脂肪细胞激素和细胞因子在能量平衡调节中的作用

肥胖与糖尿病、高血压、心脑血管疾病的发病密切相关,深入了解机体能量平衡调节机制,对防治肥胖和上述疾病有重要意义。脂肪细胞不但储能,同时通过它表达分泌各种激素和细胞因子,如瘦素(Leptin)、解偶联蛋白(UCP)及肿瘤坏死因子(TNF-α)等参与机体能量平衡的调节。脂肪细胞与胰岛之间亦有相互调节作用,并共同参与机体的糖代谢、脂肪代谢和能量代谢调节。     

重编程为心肌细胞过程中的能量代谢的研究进展

急性心肌梗死的发病率逐年上升,通过重编程细胞移植,可以促进梗死区心肌细胞再生、防治心室重构和改善心功能.但重编程效率低下,如何提高重编程的效率是目前研究的难点.代谢与细胞生命过程密切相关,心肌利用能量代谢的形式维持心脏内环境稳定和组织结构更新的物质基础,线粒体动力学参与调节能量代谢.但心肌细胞直接重编程过程中代谢机制尚未清楚.     

脓毒症时心肌能量代谢障碍机制的研究进展

心肌能量代谢障碍是导致脓毒症时心肌损伤的重要因素,但其确切的机制目前尚未完全阐明。正常情况下,线粒体是心肌能量代谢的主要场所,脂肪酸和葡萄糖氧化代谢生成的三磷酸腺苷是心脏能量的主要来源。脓毒症时,线粒体结构损伤、呼吸功能障碍、Ca2+超载、生物合成改变、自噬以及脂肪酸摄取、转运、氧化减少和葡萄糖代谢异常等导致了心肌能量代谢障碍,进而引起心肌结构损伤和功能障碍。本文主要对线粒体结构和功能异常、糖脂质代谢紊乱与脓毒症心肌能量代谢障碍关系的研究进展进行了综述。     

微波辐射对大鼠能量代谢及心肌细胞凋亡的影响

目的:探讨不同强度微波辐射对大鼠心脏的损伤作用,并初步探讨其作用机制。方法:分别以强度为500、1 000、1 500和2 000 W/m2,频率为2 450 MHz微波照射大鼠6 min,照射后6 h取大鼠心脏,检测心肌细胞中ATP含量、线粒体呼吸链复合体Ⅳ和Ⅴ活性,透射电镜观察心脏组织超微结构的改变,Muse细胞分析仪检测心肌细胞凋亡,Western blotting检测心肌细胞内cleaved caspase-3蛋白的表达。结果:随着微波辐射强度的增加,大鼠心肌细胞中ATP含量、线粒体呼吸链复合体Ⅳ和Ⅴ活性呈现降低趋势,与对照组相比,差异有统计学意义(P0.05)。透射电镜结果显示,微波辐射致细胞线粒体数量减少且形态异常,大部分线粒体溶解空化,基质明显肿胀。心肌细胞凋亡检测结果显示,微波辐射能够诱导大鼠心肌细胞发生凋亡,且随着微波辐射强度的增加,细胞凋亡率呈上升趋势(P0.05)。Western blotting结果显示,微波辐射后心肌细胞内cleaved caspase-3蛋白表达水平随着辐射强度的增加呈上升趋势(P0.05)。结论:微波辐射对大鼠心脏具有明显的损伤作用,能够引起心脏能量代谢出现异常,诱发心肌细胞发生凋亡。     

绞股蓝不同有效成分对ox-LDL诱导的内皮细胞线粒体能量代谢相关蛋白表达的影响

目的:探讨绞股蓝不同成分[绞股蓝总皂苷(Gps)、绞股蓝皂苷XLIX(GpXLIX)和人参皂苷Rb3(GRb3)]对氧化型低密度脂蛋白(ox-LDL)诱导内皮细胞线粒体能量代谢相关蛋白的影响。方法:将人脐静脉内皮细胞融合细胞EA. hy926分为对照组、模型组、Gps组、GpXLIX组和GRb3组。对照组仅用DMEM完全培养基培养;模型组予以100 mg/L ox-LDL诱导内皮细胞48 h;Gps组、GpXLIX组和GRb3组在加入100 mg/L ox-LDL作用24 h后,再分别加入100 mg/L Gps、GpXLIX和GRb3处理24 h。采用ELISA法检测各组细胞ATP含量,采用Wes全自动蛋白质印迹定量分析系统及Western blot法检测线粒体能量代谢相关蛋白细胞色素C氧化酶5a亚基(Cox5a)、NADH:泛醌氧化还原酶核心亚基S1(Ndufs1)、ATP合成酶F1亚基α(ATP5a)及细胞色素C(Cyt C)的表达。结果:与对照组比较,模型组细胞ATP含量有所降低(P<0. 01);与模型组相比,Gps组、GpXLIX组和GRb3组细胞ATP含量均不同程度...     

活性氧及能量代谢障碍在体外培养肝细胞脂肪变性中的作用

目的：探讨细胞活性氧（ROS）及线粒体能量代谢障碍在乙醇和小牛血清诱导的体外培养肝细胞脂肪变性中的作用。方法:将人肝细胞株L02进行细胞培养,加入不同浓度的乙醇,采用MTT法确定乙醇作用的最佳浓度；用2%乙醇和50%小牛血清(A+CS)诱导L02细胞，以油红O染色观察细胞内脂滴形成状况,并检测细胞TG的含量；用流式细胞仪（FCM）测定细胞活性氧及线粒体膜电位的改变；采用反相高效液相色谱分析法测定细胞ATP含量。结果:2%乙醇和50%小牛血清作用36 h,肝细胞内有典型的脂滴形成,与对照组相比，细胞内TG含量及ROS水平明显增加；而细胞线粒体膜电位及肝细胞ATP的含量则显著降低(P<0.01)。结论:在乙醇和小牛血清诱导肝细胞脂肪变过程中，细胞ROS的增加及线粒体能量代谢障碍可能发挥了重要的作用。     

急、慢性缺氧对大鼠脑线粒体能量代谢的影响

目的:探讨缺氧大鼠脑线粒体能量代谢的特点。方法:雄性Wistar大鼠随机分为急性缺氧组(AH)、慢性缺氧组(CH)和对照组。急、慢性缺氧组动物分别连续暴露于模拟4000m高原3d(AH)和40d(CH)。分离脑线粒体,分别测定线粒体呼吸功能、线粒体内腺苷酸池含量、ATP生成能力和F₀F₁-ATP酶活性。结果:急性缺氧大鼠IV态呼吸(ST₄)显著升高,伴呼吸控制率(RCR)降低,同时线粒体内ATP含量、ATP生成率和F₀F₁-ATP酶活性均显著降低;慢性缺氧大鼠ST₄、RCR、线粒体ATP含量和F₀F₁-ATP酶活性部分恢复。结论:急性缺氧脑线粒体代谢是以功能受损为特点,而慢性缺氧时则表现为功能的部分代偿。     

丹参联合黄芪对糖尿病肾病大鼠肾脏线粒体呼吸及能量代谢的影响

目的:探讨丹参联合黄芪对糖尿病肾病(DN)大鼠肾脏功能及线粒体呼吸和能量代谢的影响。方法:选择健康SD大鼠,使用链脲佐菌素制作DN大鼠模型,按随机数字表法分为DN模型组(DN组)、丹参注射液干预组(丹参组)、黄芪注射液干预组(黄芪组)、丹参联合黄芪注射液干预组(联合组)和正常对照组(对照组),每组各8只。丹参组加予丹参注射液灌胃,黄芪组加予黄芪注射液灌胃,联合组加予丹参联合注射液灌胃,正常组和DN组同时给予等量的生理盐水,连续喂养6周。检测空腹血糖、血尿素氮、血清肌酐、24小时尿量及尿蛋白定量,留取肾组织,高效液相色谱法检测ATP、ADP、AMP,提取线粒体,氧电极法检测线粒体3态呼吸速率(T3)、4态呼吸速率(T4)和呼吸控制率(RCR)。结果:与DN组大鼠比较,丹参组、黄芪组和联合组大鼠的血糖水平、血尿素氮、血清肌酐、尿蛋白定量下降,24 h尿量增加,肾脏组织线粒体T3和RCR升高,ATP、ADP含量增加,P均<0.05。但联合组与丹参组和黄芪组对比,各项指标无显著差异。结论:丹参和黄芪单用及联合可能通过改善DN大鼠肾脏线粒体呼吸功能及能量代谢,改善DN大鼠肾脏的功能。丹参联合黄芪组较单纯丹参或单纯黄芪无显著优势。     

环孢素对癫痫大鼠海马氧化应激及线粒体能量代谢的影响

 目的：探讨环孢素对癫痫大鼠海马氧化应激、线粒体膜通透性及能量代谢的影响及机制。方法：应用匹鲁卡品建立癫痫持续状态模型,检测癫痫大鼠海马在环孢素干预前后丙二醛和超氧化物歧化酶的变化;检测癫痫大鼠海马在环孢素干预前后线粒体膜通透性转换、线粒体呼吸链复合物I和III活性及ATP含量的变化。结果：环孢素抑制癫痫大鼠海马组织线粒体膜通透性转换;明显降低癫痫大鼠海马组织丙二醛的含量,提高超氧化物歧化酶的活性（P<0.05）;明显增加癫痫大鼠海马组织线粒体呼吸链复合物I活性（P<0.05）,而对粒体呼吸链复合物III活性无显著影响;明显增加癫痫大鼠海马组织ATP的含量（P<0.05）。结论：环孢素能抑制癫痫大鼠海马氧化应激反应,减轻癫痫大鼠线粒体能量代谢损伤。     

一氧化氮与脓毒性休克的关系

在脓毒性休克中,巨噬细胞和血管平滑肌细胞等细胞的诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)表达上调,使血管内皮源性舒张因子即一氧化氮(nitric oxide,NO)生成增多,引起血管过度扩张、微循环淤血、血管平滑肌对缩血管物质的反应性降低、心肌功能抑制等,导致严重的...     

一氧化氮生物利用度失调与动脉粥样硬化

内皮功能障碍与动脉粥样硬化(AS)密切相关。氧化应激、脂质浸润、炎性反应因子表达及血管张力改变等涉及一氧化氮(NO)生物利用度(内源性NO的生成和利用)的降低,在内皮功能障碍中发挥重要作用。精氨酸酶活性增强、非对称性二甲基精氨酸和同型半胱氨酸增加均能使NO生物利用度下降,促进AS发生发展。糖尿病、肥胖、慢性肾病和吸烟等通过多种方式影响NO生物利用度,参与AS的发生。     

Nitric oxide in the endometrium

Nitric oxide (NO) is an important mediator of paracrine interactions, especially within the vascular system. It is a powerful inhibitor of platelet aggregation and a potent vasodilator. NO is also a neurotransmitter and it plays a role in cell-mediated cytotoxicity. NO-generating enzymes (nitric oxide synthases, NOS) have been described in the endometrium of a number of species, suggesting that NO might be involved in endometrial function. In human endometrium, endothelial NOS and inducible NOS have been localized to glandular epithelium in the non-pregnant uterus. Weak inducible NOS immunoreactivity has been observed in decidualized stromal cells. NO might participate in the initiation and control of menstrual bleeding. Furthermore, it may play a part in the inhibition of platelet aggregation within the endometrium, where menstrual haemostasis is thought to occur primarily by vasoconstriction rather than clot organization. Endometrially derived NO could also suppress myometrial contractility. Recent attention has focused on the part that NO might play in maintaining myometrial quiescence during pregnancy. NO also appears to relax the non-pregnant myometrium, an action which could be exploited for the medical treatment of primary dysmenorrhoea.     

Nitric oxide formation in animal tissues during inflammation

Institute of Chemical Physics, Academy of Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR Yu. M. Lopukhin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 107, No. 1, pp. 31–33, January, 1989.     

Nitric oxide coordinates metabolism, growth, and development via the nuclear receptor E75

Nitric oxide gas acts as a short-range signaling molecule in a vast array of important physiological processes, many of which include major changes in gene expression. How these genomic responses are induced, however, is poorly understood. Here, using genetic and chemical manipulations, we show that nitric oxide is produced in the Drosophila prothoracic gland, where it acts via the nuclear receptor ecdysone-induced protein 75 (E75), reversing its ability to interfere with its heterodimer partner, Drosophila hormone receptor 3 (DHR3). Manipulation of these interactions leads to gross alterations in feeding behavior, fat deposition, and developmental timing. These neuroendocrine interactions and consequences appear to be conserved in vertebrates.     

Nitric oxide synthesis is increased in the endometrial tissue of women with endometriosis

BACKGROUND: Previous studies have shown that peritoneal macrophages from women with endometriosis produce excess nitric oxide (NO). This study was designed to quantify the amount of NO and determine the expression of endothelial (eNOS) and inducible NO synthases (iNOS) in women with and without endometriosis. METHODS: An enzyme-linked immunosorbent assay (ELISA) was performed on endometrial tissues obtained from controls (myoma, n = 30) and on eutopic/ectopic endometrial tissues from endometriosis patients (n = 34) to evaluate eNOS and iNOS protein concentrations in these endometrial tissues. A rapid-response chemiluminescence analyser was used to measure NO directly in fresh endometrial tissues. RESULTS: Mean (+/- SEM) levels of NO were significantly increased in the endometrial tissues of women with endometriosis (13.2 +/- 7.8 versus 19.8 +/- 12.6 nmol/g tissue; P = 0.016). Apparently higher levels of NO were found in ectopic compared with eutopic endometrium (P = 0.057). Endometrial tissues of women with endometriosis appeared to contain more iNOS than those of controls (3.6 +/- 2.2 versus 8.6 +/- 12.2 pg/ microg protein; P = 0.06), but no significant difference was found in eNOS levels. CONCLUSIONS: Greater amounts of NO and NOS are present in the endometrial tissues of women with endometriosis, implying a possible role for NO in the pathogenesis of endometriosis.     

Nitric oxide evaluation in upper and lower respiratory tracts in nasal polyposis

Background A decrease in nasal nitric oxide (NO) and an increase in exhaled NO have been demonstrated in patients with nasal polyposis (NP).
Objectives The aims were to evaluate the flux of NO from the three compartments of the respiratory tract, namely, upper nasal, lower conducting and distal airways, and to search for relationships between NO parameters and indexes of upper and lower disease activity (bronchial reactivity and obstruction). The effect of medical treatment of polyposis was also evaluated.
Methods Seventy patients with polyposis were recruited. At baseline, pulmonary function tests (spirometry, plethysmography, bronchomotor response to deep inspiration using forced oscillation measurement of resistance of respiratory system, methacholine challenge, multiple flow rates of exhaled NO and nasal NO measurements) were performed together with an assessment of polyposis [clinical, endoscopic and computed tomography (CT) scores].
Results Statistical relationships were demonstrated between nasal NO flux and severity scores (clinical: ρ=−0.31, P =0.015; endoscopic: ρ=−0.57, P <0.0001; CT: ρ=−0.46, P =0.0005), and between alveolar NO concentration and distal airflow limitation (FEF_25–75, ρ=−0.32, P =0.011). Thirty-six patients were assessed after 11 [7–13] (median [interquartile]) months of medical treatment, demonstrating an improvement in clinical and endoscopic scores, an increase in nasal NO flux, a decrease in NO flux from conducting airways, an improvement in the mild airflow limitation (forced expiratory volume in 1 s, FEF_25–75, even in non-asthmatic patients) and a decrease in the bronchoconstrictor effect of deep inspiration.
Conclusions The medical treatment of NP improves both airway reactivity and obstruction, whatever the presence of asthma, suggesting a functional link between upper and lower airway functions.     

精-甘-天冬-丝氨酸肽对兔血管舒张功能及左旋精氨酸/一氧化氮途径的影响

本文观察了RGDS肽对兔离体股动脉舒张反应、主动脉一氧化氮(NO)生成、一氧化氮合酶(NOS)活性及左旋精氨酸(L-Arg)转运的影响。结果发现,RGDS肽呈剂量依赖性地引起内皮依赖和非依赖性的血管扩张;增加NOS活性及NO的产生,可被L-NNA所逆转。RGDS肽亦可增加血管组织高和低亲和性L-Arg的最大转运速率(与对照组相比分别增加126%和64%,P＜0.05和P＜0.01)。表明RGDS肽可显著增加L-Arg转运及NOS的活性,对内皮衍化舒张因子(EDRF)/NO系统具有重要调节作用。