HPLC测定熊胆滴眼剂中牛磺熊去氧胆酸的含量

目的：建立熊胆滴眼剂中牛磺熊去氧胆酸的测定方法。方法;采用ＨＰＬＣ测定熊胆滴眼剂中牛磺熊去氧胆酸的含量,以中性氧化铝吸附黄芩甙除干扰,达到了很好的分离效果。结果：平均回收率９７．２６％,ＲＳＤ１．４９％。结论：本和法简便、快速、准确、重复性好。     

内质网功能状态对卵巢癌细胞顺铂敏感度的影响

目的 探讨内质网应激（endoplasmic reticulum stress, ERS）功能状态对卵巢癌细胞顺铂（DDP）敏感度的影响。方法 卵巢癌细胞系SKOV3接受40 μmol/L DDP处理24 h后, qRT-PCR检测ERS相关基因改变;同时内质网示踪染料（ER-tracker）观察内质网形态变化;分别用ERS稳定剂牛磺熊去氧胆酸钠（tauroursodeoxycholate, TUDCA）或ERS诱导剂毒胡萝卜素（thapsigargin, TG）预处理SKOV3,再接受DDP处理,应用流式细胞术检测细胞凋亡率;应用Western blot法检测内质网应激相关蛋白GRP78和CHOP是否表达;从临床卵巢癌患者腹水中分离与培养原代卵巢癌细胞后,采用流式细胞术比较TUDCA及TG预处理对原代卵巢癌细胞DDP敏感度影响,Western blot法检测凋亡相关蛋白PARP和Caspase-3的变化。结果 顺铂处理卵巢癌细胞系SKOV3后能够引起明显的ERS,ERS相关蛋白明显上调,内质网形态呈现颗粒化;TUDCA可以显著下调DDP引起的杀伤作用（P<0.05）,显著降低GRP78和CHOP蛋白水平;TG可以显著上调DDP引起的杀伤作用（P<0.05）、GRP78和CHOP蛋白水平;在卵巢癌腹水原代细胞中TUDCA亦可显著抑制DDP引起的杀伤作用（P<0.05）,TG亦可显著上调DDP引起的杀伤作用（P<0.05）。结论 改变ERS的功能状态能够影响卵巢癌细胞对顺铂的敏感度。     

The unfolded protein response in retinal vascular diseases: Implications and therapeutic potential beyond protein folding

Angiogenesis is a complex, step-wise process of new vessel formation that is involved in both normal embryonic development as well as postnatal pathological processes, such as cancer, cardiovascular disease, and diabetes. Aberrant blood vessel growth, also known as neovascularization, in the retina and the choroid is a major cause of vision loss in severe eye diseases, such as diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, and central and branch retinal vein occlusion. Yet, retinal neovascularization is causally and dynamically associated with vasodegeneration, ischemia, and vascular remodeling in retinal tissues. Understanding the mechanisms of retinal neovascularization is an urgent unmet need for developing new treatments for these devastating diseases. Accumulating evidence suggests a vital role for the unfolded protein response (UPR) in regulation of angiogenesis, in part through coordinating the secretion of pro-angiogenic growth factors, such as VEGF, and modulating endothelial cell survival and activity. Herein, we summarize current research in the context of endoplasmic reticulum (ER) stress and UPR signaling in retinal angiogenesis and vascular remodeling, highlighting potential implications of targeting these stress response pathways in the prevention and treatment of retinal vascular diseases that result in visual deficits and blindness.     

滔罗特用于预防胆囊结石复发的临床效果分析

目的 分析行保胆取石术的患者术后口服滔罗特对预防结石复发的效果,以及对不同种类结石的预防效果有何差异.方法 收集我院2010年3月~2012年10月行保胆取石术的患者共289例,其中给予术后口服滔罗特的174例,未服用滔罗特的115例,分别作为治疗组和对照组,随访1年,统计分析结石复发率.结果 在1年随访期内,治疗组复发5例,未复发169例,复发率为2.9%,对照组复发12例,未复发103例,复发率为10.4%,两组复发率有显著差异（P＜0.05）.对于胆固醇性结石,治疗组的复发率明显低于对照组（P＜0.05）;而对于胆色素性结石,两组复发率差异不显著（P＞0.05）.结论 术后口服滔罗特对降低结石复发率有一定积极作用,尤其对于胆固醇性结石效果较明显.     

UPLC-MS-based serum metabonomics for identifying acute liver injury biomarkers in Chinese miniature pigs

Metabonomics has emerged as an important technology for exploring the underlying mechanisms of diseases and screening for biomarkers. In this investigation, to comprehensively assess metabolite changes in d-galactosamine (GalN)-induced liver injury in Chinese miniature pigs and to increase our understanding of physiological changes in normal and pathological states, we used ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to analyze metabolites and identify biomarkers in serum. Blood samples were collected both from 18 h after GalN treatment group and control group pigs. We performed multivariate analyses on the metabolite profiles to identify potential biomarkers of acute liver injury, which were then confirmed by tandem MS. Based on “variable of importance in the project” (VIP) values and S-plots, four groups of biomarkers were identified – namely conjugated bile acids, lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs) and fatty acid amides (FAAs) – that were present at significantly different levels in the control and GalN-induced groups. LPCs, PCs, and FAAs showed marked decreases in the GalN-treated group, whereas conjugated bile acids in the treated group showed considerable increases. Taken together, our results suggested that obvious metabolic disturbances occur during acute liver injury, which provided novel insights into the molecular mechanism(s) of d-galactosamine (GalN)-induced liver injury, and will facilitate future research and management of liver injury.     

牛磺熊去氧胆酸对谷丙转氨酶活性的影响

通过测定谷丙转氨酶（ＧＰＴ）活力的方法,观察了牛磺熊去氧胆酸（ＴＵＤＣＡ）对ＧＰＴ的作用。发现ＴＵＤＣＡ对ＧＰＴ呈抑制作用。且随其浓度的增加,抑制作用增强,当ＴＵＤＣＡ浓度为０．８３３ｍｇ／ｍｌ时,对ＧＰＴ的抑制率达到８１％。动力学实验还表明,增加底物浓度,并不能消除ＴＵＤＣＡ对ＧＰＴ活力的抑制作用,Ｋｍ值不变,Ｖｍ值作减小,Ｋｍ／Ｖｍ值增大,呈现出非竞争性抑制作用。同时用ＣＣｌ４小鼠肝损伤模型,     

Cellular responses following retinal injuries and therapeutic approaches for neurodegenerative diseases

Retinal neurodegenerative diseases like age-related macular degeneration, glaucoma, diabetic retinopathy and retinitis pigmentosa each have a different etiology and pathogenesis. However, at the cellular and molecular level, the response to retinal injury is similar in all of them, and results in morphological and functional impairment of retinal cells. This retinal degeneration may be triggered by gene defects, increased intraocular pressure, high levels of blood glucose, other types of stress or aging, but they all frequently induce a set of cell signals that lead to well-established and similar morphological and functional changes, including controlled cell death and retinal remodeling. Interestingly, an inflammatory response, oxidative stress and activation of apoptotic pathways are common features in all these diseases. Furthermore, it is important to note the relevant role of glial cells, including astrocytes, Müller cells and microglia, because their response to injury is decisive for maintaining the health of the retina or its degeneration. Several therapeutic approaches have been developed to preserve retinal function or restore eyesight in pathological conditions. In this context, neuroprotective compounds, gene therapy, cell transplantation or artificial devices should be applied at the appropriate stage of retinal degeneration to obtain successful results. This review provides an overview of the common and distinctive features of retinal neurodegenerative diseases, including the molecular, anatomical and functional changes caused by the cellular response to damage, in order to establish appropriate treatments for these pathologies.