三磷酸腺苷脂质体的研究进展

本文综述了近年来三磷酸腺苷(ATP)脂质体的研究进展.脂质体作为新载体可以提高ATP在体内的稳定性,并且能靶向于缺血的心肌和缺血的大脑,用于器官移植中能提高冷冻贮存器官的能级状态,提高移植的成活率,故制备稳定的ATP脂质体具有重要的意义.本文还综述了ATP脂质体的制备方法,探讨如何进一步提高脂质体的包裹率和靶向性,以用于临床.     

三磷酸腺苷抑制肿瘤坏死因子-α诱导的肌源性干细胞凋亡及机制

目的 探讨三磷酸腺苷(ATP)对肌源性干细胞(MDSCs)凋亡的抑制作用及其机制.方法 采用差速贴壁法分离新生小鼠MDSCs,利用40μg/L肿瘤坏死因子(TNF)-α诱导MDSCs凋亡,100 μmol/L ATP抑制细胞凋亡.经流式细胞仪检测MDSCs的凋亡率和半胱氨酰天冬氨酸特异性蛋白酶( Caspase) -3/8的表达.结果 TNF-α诱导后,脱壁细胞明显增多,MDSCs的凋亡率由5.17％升至31.58％,增加了5倍,Caspase-3染色阳性细胞率由5.01％增至19.25％,Caspase-8染色阳性细胞率由2.97％增至8.58％.ATP作用后,MDSCs的凋亡率降至12.06％,减少了2/3,Caspase-3染色阳性细胞率降至9.86％,Caspase-8染色阳性细胞率降至6.96％,但仍高于对照组.结论 ATP能抑制MDSCs表达Caspase-3/8,减轻TNF-α诱导的MDSCs凋亡.     

Mesenteric lymph duct ligation after hemorrhagic shock enhances the ATP level and ATPase activity in rat kidneys

Background: Kidney injury commonly occurs following hemorrhagic shock. This study aims to observe the effects of mesenteric lymph duct ligation (MLDL) on the adenosine triphosphate (ATP) levels and the cell membrane adenosine triphosphatase (ATPase) activity in the kidneys of rats subjected to hemorrhagic shock. Methods: Wistar rats were assigned into sham, shock, and ligation groups. The hemorrhagic shock model was established in the shock and ligation groups, and MLDL was performed in the ligation group after resuscitation. Renal homogenates were prepared to determine the ATP and ATPase levels at 90?min after hemorrhage and at 0, 1, 3, 6, 12, and 24?h after resuscitation. Results: The ATP levels, and the Na⁺–K⁺–ATPase, Mg²⁺–ATPase, Ca²⁺–ATPase, and Ca²⁺–Mg²⁺–ATPase activities in the renal tissue of the shock group were lower than those in the sham group at the multiple time points. Furthermore, the corresponding values in the ligation group were significantly higher than those in the shock group at multiple time points. Conclusion: MLDL improves energy metabolism and enhances the ATPase activity in the kidneys of hemorrhagic shock rats, along with other mechanisms that alleviate renal injury after hemorrhagic shock.     

负荷-静息99Tcm-MIBI门控心肌灌注断层显像相位分析评价左室缺血心肌收缩同步性

目的 以99 Tcm-MIBI门控心肌灌注断层显像(GSMPI)相位分析探讨不同缺血灌注状态下左室心肌收缩同步性.方法 回顾性分析129例[男65例,女64例,年龄48～88(68.6±10.2)岁]行99 Tcm-MIBI两日法静息-负荷GSMPI患者的心肌灌注及心功能数据.采用17节段5分制对图像进行评分,获得负荷总积分及心肌缺血积分,分为灌注正常组及灌注异常组,后者再分为可逆性灌注缺损组及固定性灌注缺损组.采用两独立样本t检验比较分析各组间GSMPI的PSD和PHB,各组内静息与负荷PSD及PHB间差异的比较采用配对t检验.结果 129例患者中,灌注正常组66例,灌注异常组63例,其中可逆性灌注缺损组39例,固定性灌注缺损组24例.灌注异常组PSD及PHB显著大于灌注正常组,分别为18.3±7.8和14.3±6.6,68.6±30.9和50.2±20.0(t=-3.110和-3.989,均P＜0.05).尽管固定性灌注缺损组的PSD和PHB较可逆性灌注缺损组有增大趋势,但差异均无统计学意义(=-1.554～-0.408,均P＞0.05);两亚组静息和负荷PSD和PHB间亦无明显差异(t=-0.961 ～-0.114,均P＞0.05).LVEF≤60％组的静息和负荷PSD(20.4±8.1和20.8±6.4)均显著大于LVEF＞ 60％组(15.0±6.8和15.3±7.0;t=3.642和3.886,均P＜0.05);LVEF≤60％组的静息和负荷PHB (77.8±53.5和78.4±26.7)也显著大于LVEF＞60％组(53.5±23.0和55.9±24.5;t=4.567和4.302,均P＜0.05).结论 99Tcm-MIBI GSMPI相位分析能够反映血流灌注异常对心肌收缩同步性的损害及由此造成的对左室整体收缩功能的影响,可在一定程度上反映不同心肌缺血状态下左室收缩同步性的差异;就99Tcm-MIBI而言,负荷和静息GSMPI相位分析对左室收缩同步性评估的价值相当.     

Effects of intravenous adenosine 5′-triphosphate on intraoperative hemodynamics and postoperative pain in patients undergoing major orofacial surgery: a double-blind placebo-controlled study

Purpose  We conducted a double-blind placebo-controlled study to investigate the effects of the intraoperative intravenous infusion of adenosine 5′-triphosphate (ATP) on intraoperative hemodynamics and postoperative pain in patients undergoing major orofacial surgery. Methods  Thirty patients (age, 16–42 years; 16 males/14 females) scheduled for sagittal split ramus osteotomy were assigned in a double-blind fashion to receive intraoperative intravenous infusion of ATP (n = 15) or saline (n = 15). Anesthesia was induced and maintained with propofol, fentanyl, and vecuronium. Local anesthesia was added for intraoperative analgesia. In the ATP group, ATP was infused at a rate of 160 μg·kg⁻¹·min⁻¹ throughout surgery. Postoperative pain was managed with intravenous patient-controlled analgesia (PCA) with morphine. The intensity of postoperative pain was assessed with a verbal numeric rating scale (NRS). Morphine consumption was also assessed. Results  There were no differences in demographic, anesthetic, and surgical data between the ATP and placebo groups. Intraoperatively, ATP effectively suppressed responses of blood pressure and heart rate to painful surgical stimuli. There were no differences in postoperative NRS scores between the two groups. However, postoperative morphine consumption was significantly less in the ATP group, compared with the placebo group, throughout the 72-h postoperative observation period. Cumulative morphine consumption for 72 h postoperatively was 47% less with ATP, compared with placebo. No adverse effect of ATP was observed. Conclusion  Our data suggest that intraoperative ATP infusion can blunt hemodynamic responses to surgical stimuli and produce prolonged analgesia in patients undergoing major orofacial surgery.     

大鼠嘌呤P2Y2受体在神经系统分布的实验研究

目的探讨P2Y2受体在脊髓、背根神经节和坐骨神经的表达和具体分布，研究三磷酸腺苷（adenosine triphosphate．ATP）对神经再生的作用机制提供理论基础。方法将6只SD乳鼠的脊髓、背根神经节和坐骨神经标本置于含有0．1％二乙基焦碳酸的4%多聚甲醛液中快速固定、石蜡包埋、超薄切片。实验组：根据P2Y2受体mRNA的碱基序列，制作非放射性标记的核苷酸探针，原位杂交后将切片置于含有NBT溶液（50mg／ml硝基兰四唑溶于二甲基甲酰胺）、BCIP溶液（75mg／ml溴绿一吲哚磷酸溶于二甲基酰胺）的检测缓冲液中染色，镜下观察P2Y2受体的具体分布。对照组：切片刚不含探针的杂交缓冲液覆盖、染色观察。结果实验组：脊髓灰质前角神经元胞浆中可见P2Y2受体的表达，呈弱阳性；背根神经节雪旺细胞的胞浆和胞核中均可见P2Y2受体的表达，且呈强阳性；对照组：无P2Y2受体表达。实验组与对照组坐骨神经原位杂交尢P2Y2受体的表达。结论P2Y2受体主要分布在脊髓、背根神经节，细胞外ATP可以通过P2Y2受体作用于脊髓和背根神经节细胞。     

丙泊酚对大鼠脑缺血-再灌注损伤后海马线粒体ATP含量和ATP酶活性的影响

目的观察丙泊酚对大鼠脑缺血-再灌注损伤后海马线粒体三磷酸腺苷（ATP）含量、ATP酶活性、脂质过氧化和超微结构的影响.方法采用大鼠全脑缺血-再灌注损伤模型.40只Wistar大鼠随机分为假手术组（A组）、缺血-再灌注对照组（B组）和缺血-再灌注丙泊酚预处理组,后者按丙泊酚用量又分为50 mg/kg（C1组）、100 mg/kg（C2组）和150 mg/kg（C3组）三个亚组.观察全脑缺血10 min再灌注60 min时海马线粒体的超微结构、ATP和丙二醛（MDA）的含量及Na^＋-K^＋-ATP酶、Ca^2＋-ATP酶、超氧化物歧化酶（SOD）和谷光甘肽（GSH）活性的变化.结果与B组比较,丙泊酚各处理组海马线粒体的ATP含量、Na^＋-K^＋-ATP酶、Ca^2＋-ATP酶、SOD和GSH的活性均有不同程度的增高（P〈0.05或0.01）,MDA含量有不同程度的降低（P〈0.05或0.01）,线粒体超微结构的损伤程度亦明显减轻.结论丙泊酚对脑缺血-再灌注损伤的保护效应可能与其抑制线粒体脂质过氧化反应,减轻线粒体的损伤,促进线粒体ATP含量和ATP酶活性的恢复有关.     

内脏分布的P2X受体的功能与疾病

P2X受体是细胞外配体门控的阳离子通道,目前普遍认为可分为7个亚型,即P2X1~P2X7,当任何一种亚型的P2X受体与胞外三磷酸腺苷结合时,P2X通道打开,允许阳离子通过,如钠、钾、钙离子等(但以钙离子的通透性为著),继而引起一系列生理或病理现象。P2X受体在体内分布广泛,涉及到呼吸、消化、心血管、泌尿生殖以及骨骼肌肉系统和神经系统。     

平滑肌细胞双信使系统与钙火花相关性研究

在平滑肌细胞的肌醇脂质代谢中产生的肌醇三磷酸(IP3)和二酰甘油(DAG)是胞内重要的第二信使,由它们激动的IP3/Ca2+和DAG/蛋白激酶C(PKC)途径,即是调控胞内许多生理过程的重要信号途径。因此又把这一以肌醇磷脂代谢为基础的细胞信号系统称为“双信使系统”。大量研究表明,双信使系统与平滑肌细胞胞内Ca2+浓度的调节、胞内局部Ca2+释放事件、钙火花的产生和调控紧密相关。本文就此方面的研究进展进行综述。     

P2Y受体与三叉神经痛之间的关系

腺苷三磷酸(ATP)作为一种重要的神经递质具有广泛的生物学效应。多种伤害性刺激均可引起三叉神经节(TG)神经元释放ATP,ATP激活P2受体可引起疼痛。P2受体又分为P2X和P2Y两类。在受损的TG神经元上,P2Y受体的表达明显增多。本文就ATP与P2Y受体表达间的相关性、P2Y受体在TG中的信号转导机制、P2Y受体对神经损伤性痛觉信号的转导作用等研究进展作一综述。