家兔急性缺氧后左心室舒张功能和心肌细胞内钙转运及能量代谢的研究

为探讨急性缺氧对家兔左心室舒张功能、心肌细胞内钙转运和能量代谢的影响。将２３只家兔分为对照组（６只）、吸入５％低氧混合气的缺氧１组（Ｈ１）（１２只）、吸入１０％低氧混合气的缺氧２组（Ｈ２）（５只），用心导管法测定左心室压力下降最大速率（ＬＶｄｐ／ｄｔｍａｘ）和压力下降时间常数（Ｔ值）；测定心肌肌浆网（ＳＲ）钙ＡＴＰ酶活性、心肌ＳＲ摄钙量、心肌组织ＡＴＰ和磷酸肌酸（ＣｒＰ）。结果，缺氧后ＬＶｄｐ／ｄｔｍａｘ下降，Ｔ值延长；缺氧组心肌ＳＲ钙ＡＴＰ酶活性及摄钙量下降；心肌线粒体钙含量升高；心肌组织ＡＴＰ和ＣｒＰ下降，心肌组织ＡＴＰ与线粒体钙含量呈负相关。提示，急性缺氧可引起左心室舒张功能障碍并影响心肌ＳＲ钙转运和心肌能量代谢。     

Abrogated energy-dependent uptake of cisplatin in a cisplatin-resistant subline of the human ovarian cancer cell line IGROV-1

The parental IGROV-1 human ovarian adenocarcinoma cell line was intermittently exposed to increasing concentrations of cisplatin to obtain resistant sublines. A stable resistant subline with a resistance factor of 8.4 had been developed after 9 months and 28 passages, which was denoted IGROV_CDDP. A high correlation coefficient of 0.97 was found between the log cell survival and the DNA-adduct peak level during the process of resistance development. IGROV_CDDP was strongly cross-resistant to carboplatin and doxorubicin and moderately cross-resistant to etoposide, docetaxel, and topotecan. Only minor resistance against 5-fluorouracil was observed, whereas IGROV_CDDP was not cross-resistant to methotrexate. Intracellular accumulation of cisplatin was 65% lower in IGROV_CDDP as compared with parental IGROV-1 at 37  °C under normal conditions. Coincubation of cisplatin with the Na⁺/K⁺-ATPase inhibitor ouabain resulted in a more pronounced decrease in platinum accumulation in IGROV-1 (44% decrease) than in IGROV_CDDP (26% decrease). Under energy-depleting conditions the accumulation of cisplatin in the parental cell line was approximately 60% lower than that observed under normal (energy [i.e., ATP] rich) culture conditions. In contrast, the accumulation in IGROV_CDDP was not affected by ATP-depletion. There appeared to be no significant difference between the intracellular accumulation of platinum in the resistant and sensitive cells under conditions of energy deprivation or when the uptake was studied at 0  °C. In conclusion, abrogation of energy-dependent accumulation in IGROV_CDDP seems to be a major mechanism of resistance to cisplatin in this cell line. Received: 21 January 1997 / Accepted: 22 July 1997     

1-Methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol) is toxic to dopaminergic neuroblastoma SH-SY5Y cells via impairment of cellular energy metabolism

The endogenous neurotoxin 1-methyl-6,7-dihydroxy-1,2,3, 4-tetrahydroisoquinoline (salsolinol), which is structurally similar to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has been reported to inhibit mitochondrial complex I (NADH-Q reductase) activity as does the MPTP metabolite 1-methyl-4-phenylpyridinium ion (MPP(+)). However, the mechanism of salsolinol leading to neuronal cell death is still unknown. Thus, we correlated indices of cellular energy production and cell viability in human dopaminergic neuroblastoma SH-SY5Y cells after exposure to salsolinol and compared these results with data obtained with MPP(+). Both toxins induce time and dose-dependent decrease in cell survival with IC(50) values of 34 microM and 94 microM after 72 h for salsolinol and MPP(+), respectively. Furthermore, salsolinol and MPP(+) produce a decrease of intracellular net ATP content with IC(50) values of 62 microM and 66 microM after 48 h, respectively. In contrast to MPP(+), salsolinol does not induce an increase of intracellular net NADH content. In addition, enhancing glycolysis by adding D-glucose to the culture medium protects the cells against MPP(+) but not salsolinol induced cellular ATP depletion and cytotoxicity. These results suggest that cell death induced by salsolinol is due to impairment of cellular energy supply, caused in particular by inhibition of mitochondrial complex II (succinate-Q reductase), but not complex I.     

Long-term effects on feeding and body weight after stimulation of forebrain or hindbrain CRH receptors with urocortin

Research on the contribution of CRH receptor stimulation to energy homeostasis has focused on forebrain substrates. In this study, we explored the effects of caudal brainstem administration of the CRH receptor agonist, urocortin, on food intake and body weight, and on plasma glucose and corticosterone (CORT) in non-deprived rats. Urocortin (0, 0.3, 1, 3 microg) delivered, respectively, to the fourth and lateral ventricles yielded substantial suppression of food intake measured 2, 4 and 24 h later. A significant but more modest anorexia was observed between 24 and 48 h after injection. Intake responses did not differ between the injection sites, but body weight loss measured 24 h after lateral-i.c.v. injection was substantially greater than that after fourth-i.c.v. injection. Fourth-i.c.v. urocortin administration (3 microg) produced substantial elevations in plasma glucose and CORT that were not distinguishable in magnitude and duration from responses to lateral-i.c.v. delivery. Unilateral microinjection of urocortin into the dorsal vagal complex significantly reduced 24-h food intake at a dose (0.1 microg) that was subthreshold for the response to ventricular administration, suggesting that fourth-i.c.v. effects are mediated in part by stimulation of CRH receptors in this region of the caudal brainstem. The results indicate that similar effects can be obtained from stimulation of anatomically disparate populations of CRH receptors, and that interactions between forebrain and hindbrain structures should be considered in the evaluation of CRH contributions to food intake and body weight control.     

GR-100T/GR-200A双元件热释光剂量计的实用性探讨

目的探讨GR-100T/GR-200A双元件热释光剂量计(TLD)在个人剂量监测中的实用性.方法使用RGD-3B和UD-512A热释光剂量仪、GR-100T和GR-200A元件等进行相关实验分析.结果 GR-100T/GR-200A双元件TLD能鉴别出30～1250keV的光子能量,并可测量出几μGy的低水平剂量;有0.1mmCu过滤时,该TLD中GR-100T/GR-200A相对能量响应比值几乎呈线性下降,在30～40keV能量范围内由19.5降低到13.5,对低能范围光子能量的估算非常灵敏.结论该TLD能实现能量鉴别和低水平Hp(d)测量的双重目的,其成本低、组合方便,在个人剂量监测中有一定的实用性.     

水通道蛋白-9与脑部疾病

水通道蛋白-9(AQP9)是水通道蛋白家族中特殊的一员,对水和多种中性溶质均具有转运活性.AQP9在脑内主要分布于神经胶质细胞、内皮细胞和儿茶酚胺能神经元.目前AQP9在脑内的功能还不完全清楚,初步认为除维持脑内水代谢平衡外,还可能在能量代谢方面发挥重要作用.AQP9与脑部涉及水或能量代谢的疾病如脑血管病、帕金森病和脑肿瘤等密切相关.     

超早期针刺百会、水沟对急性脑缺血大鼠能量代谢的影响

目的观察针刺抗脑缺血损伤的作用机理。方法采用微创开颅电凝法制作大鼠急性脑缺血模型,70只大鼠按随机数字表法分为7组：正常组、模型2h组、模型24h组,穴位2h组、非穴位2h组、穴位24h组、非穴位24h组,每组10只。针刺百会、水沟（频率120次／min,捻转泻法1min,5mird次,留针30min）。非穴位针刺分别在百会、水沟左侧旁开5mm处进针．手法同穴位针刺。穴位24h组及非穴位24h组在24h再针刺1次。采用高效液相检测各组缺血脑组织ATP、ADP、AMP含量,比色法检测缺血脑组织Na＋-K＋ATP酶、Ca2＋ATP酶含量。结果造模成功后,脑组织ATP、ADP、Na＋-K＋ATP酶和Ca2＋ATP酶含量在大鼠脑缺血后2h后即明显下降,AMP含量明显升高,与正常组比较。差异明显（P〈0．01）,且缺血24h后尤为显著,与2h比较有极显著差异（P〈0．叭）;穴位组大鼠ATP、ADP、Na＋-K＋ATP酶和Ca2＋ATP酶含量较模型组及非穴位组比较明显升高,AMP含量下降,有极显著差异（P〈0．01）,并且穴位2h组优于24h组,有显著差异（P〈0．05）;相同时间点非穴位组与模型组比较,无显著差异（P〉0．05）。结论穴位针刺可以有效改善脑缺血大鼠脑组织能量代谢,发挥抗脑缺血损伤的作用,进一步为临床针刺抗脑缺血提供实验依据。     

促分裂原活化的蛋白激酶信号通路与能量代谢的关系

能量代谢每时每刻都伴随着物质代谢在生命体内发生。生物通过利用物质代谢产生的高能磷酸化合物以维持各项生命功能的运转,不同状态下的细胞通过利用各种物质通过不同的通路进行不同的代谢方式。促分裂原活化的蛋白激酶(MAPK)通路作为生命体里广泛存在的一类信号蛋白,影响着细胞、生物体的生命活动。MAPK通路在能量代谢的各个环节起着非常重要的作用。通过研究MAPK通路中的胞外信号调节激酶(ERK)通路、Jun激酶(JNK)通路、P38通路均与能量代谢有关的蛋白、靶点、关键酶、转运体,与三大营养物质能量代谢相结合,从而为能量代谢相关的细胞功能进一步研究铺垫,并为今后治疗肿瘤性疾病、感染性疾病、代谢性疾病等提供新思路。     

A Novel Preparation of Special-Shaped Phosphors-in-Glass by Gel Casting with Isobam for High-Power WLEDs Lighting

Phosphors-in-glass (PiGs) regarded as a promising phosphor-converter for white light emitting diodes (WLEDs) is being researched widely. However, there are few reports on the effect of changing the shape of PiGs on the color rendering index (CRI) and heat dissipation of WLEDs. In this paper, gel casting with Isobam was first attempted in preparing special-shaped PiGs successfully. It exhibited that 76 wt.% was the optimum solid content based on the rheological properties of slurry and the shrinkage of green bodies. The sintering rate should be kept at a low speed and glass transition temperature (Tg) of glass powders must be higher than sublimation temperatures (Ts) of APS and Isobam. The CRI of PiGs was increased by about 27% after changing the shape of PiGs from cylinder to dome. Most importantly, operating temperature also reduced effectively the increase of the surface area of PiGs. Therefore, changing the shape of PiGs by gel casting with Isobam is a creative way for high-power WLEDs lighting.     

阻塞性睡眠呼吸暂停低通气综合征与成纤维细胞生长因子21

阻塞性睡眠呼吸暂停低通气综合征（OSAHS）发病率逐年升高,已经成为危害人类健康的主要疾病之一。迄今为止,OSAHS 的发病机制尚未阐明。成纤维细胞生长因子21（FGF21）是参与糖脂代谢的一种重要蛋白质。近年来大量的研究显示 FGF21与 OSAHS 的发生发展有密切的联系。本文就近些年 OSAHS 与 FGF21的相关研究进行简要综述。