液质联用技术联合网络药理学探讨白鲜皮治疗湿疹的作用机制＊

目的 采用液质联用技术分析白鲜皮中的主要化学成分；基于网络药理学技术研究白鲜皮治疗皮肤湿疹的活性成分、作用靶点及作用机制。方法 利用液质联用技术（LC-MS）对白鲜皮主要成分进行分析，通过质谱数据结合文献资料，对各主要成分进行快速识别；通过利用SwissADME数据库对白鲜皮潜在活性成分进行预测，筛选主要作用靶点。进行KEGG通路富集分析，最终得到白鲜皮成分-靶点-疾病-通路网络图。采用分子对接技术对主要成分和作用靶点进行验证。结果 从白鲜皮中共分析鉴定了12种成分，进一步筛选得到4种潜在活性成分，可作用于48个关键靶点和14条主要通路。结论 采用LC-MS技术结合网络药理学方法，可以快速分析白鲜皮的潜在活性成分，并初步揭示了成分-靶点-通路之间的关系。通过分子对接技术可以做作用靶点进行验证。     

Early life Adversity,functional connectivity and cognitive performance in Schizophrenia: The mediating role of IL-6

ObjectiveExposure to childhood trauma (CT) is associated with cognitive impairment in schizophrenia, and deficits in social cognition in particular. Here, we sought to test whether IL-6 mediated the association between CT and social cognition both directly, and sequentially via altered default mode network (DMN) connectivity.MethodsThree-hundred-and-eleven participants (104 patients and 207 healthy participants) were included, with MRI data acquired in a subset of n = 147. CT was measured using the childhood trauma questionnaire (CTQ). IL-6 was measured in both plasma and in toll like receptor (TLR) stimulated whole blood. The CANTAB emotion recognition task (ERT) was administered to assess social cognition, and cortical connectivity was assessed based on resting DMN connectivity.ResultsHigher IL-6 levels, measured both in plasma and in toll-like receptor (TLR-2) stimulated blood, were significantly correlated with higher CTQ scores and lower cognitive and social cognitive function. Plasma IL-6 was further observed to partly mediate the association between higher CT scores and lower emotion recognition performance (CTQ total: β_indirect −0.0234, 95% CI: −0.0573 to −0.0074; CTQ physical neglect: β_indirect = −0.0316, 95% CI: −0.0741 to −0.0049). Finally, sequential mediation was observed between plasma IL-6 levels and DMN connectivity in mediating the effects of higher CTQ on lower social cognitive function (β_indirect = −0.0618, 95% CI: −0.1523 to −0.285).ConclusionThis work suggests that previous associations between CT and social cognition may be partly mediated via an increased inflammatory response. IL-6′s association with changes in DMN activity further suggest at least one cortical network via which CT related effects on cognition may be transmitted.     

Fusion of white and gray matter geometry: A framework for investigating brain development

Current neuroimaging investigation of the white matter typically focuses on measurements derived from diffusion tensor imaging, such as fractional anisotropy (FA). In contrast, imaging studies of the gray matter oftentimes focus on morphological features such as cortical thickness, folding and surface curvature. As a result, it is not clear how to combine findings from these two types of approaches in order to obtain a consistent picture of morphological changes in both gray and white matter.In this paper, we propose a joint investigation of gray and white matter morphology by combining geometrical information from white and the gray matter. To achieve this, we first introduce a novel method for computing multi-scale white matter tract geometry. Its formulation is based on the differential geometry of curve sets and is easily incorporated into a continuous scale-space framework.We then incorporate this method into a novel framework for “fusing” white and gray matter geometrical information. Given a set of fiber tracts originating in a particular cortical region, the key idea is to compute two scalar fields that represent geometrical characteristics of the white matter and of the surface of the cortical region. A quantitative marker is created by combining the distributions of these scalar values using Mutual Information. This marker can be then used in the study of normal and pathological brain structure and development. We apply this framework to a study on autism spectrum disorder in children. Our preliminary results support the view that autism may be characterized by early brain overgrowth, followed by reduced or arrested growth (Courchesne, 2004).     

UPLC-Q-TOF-MS对桑白皮总黄酮提取物的快速分析

目的:对桑白皮总黄酮提取物中的各化合物进行快速的分离和鉴定,并对其主要的裂解碎片和二级裂解规律进行探讨。方法:采用超高效液相串联四级杆飞行时间质谱联用技术(UPLC-Q-TOF-MS),在电喷雾离子源(ESI)负离子模式下进行分离和检测;使用Waters公司BRH分析柱(2.1 mm×50 mm,1.7μm);以0.1%甲酸水为流动相A,乙腈为流动相B,梯度洗脱;流速0.3 m L·min~(-1);柱温为25℃。结果:基于UPLC-Q-TOF-MS技术分离所得精确相对分子质量,结合二级质谱裂解信息,使用Masslynx 4.1软件对数据进行统计和分析,并参考Sci Finder数据库(美国化学学会在线数据库学术版),桑白皮总黄酮提取物中共鉴定出13种黄酮成分,其中有7个Diels-Alder加合物,主要代表物为桑根酮C(sanggenon C),桑根酮D(sanggenon D),6种异戊烯基黄酮类化合物,代表物为桑辛素(morusin)。结论:通过超高效液相的分离,首次发现了桑白皮总黄酮提取物中的化合物在ESI源中脱去H_2和H_2O的现象,并对其二级裂解碎片的规律进行探讨,同时也为桑白皮总黄酮提取物的成分鉴定提供了一个快速、简便、可靠的方法。     

关黄柏炒炭前后饮片化学成分的变化规律分析

目的:探究关黄柏炒炭前后饮片化学成分的变化规律,为关黄柏和关黄柏炭饮片的质量标准制定提供依据。方法:采用HPLC测定,流动相乙腈-0.4 mol·L~(-1)氯化铵水溶液梯度洗脱,柱温35℃,流速1.0 m L·min~(-1),检测波长215 nm。分析关黄柏炒炭前后饮片化学成分组成及含量的变化,对其中7种主要化学成分进行定量分析。结果:10批关黄柏饮片中,木兰花碱、盐酸黄柏碱、盐酸药根碱、盐酸巴马汀、盐酸小檗碱、黄柏内酯、黄柏酮的质量分数分别为2.468~6.783,1.947~4.197,0.209~0.506,3.049~4.557,5.869~13.168,5.141~7.337,1.798~4.975 mg·g~(-1)。关黄柏炒炭后,除个别企业样品外,各化学成分含量均有减少,其中盐酸小檗碱、盐酸巴马汀等生物碱类成分几乎殆尽;黄柏酮、黄柏内酯等小极性成分保存较多,9批关黄柏炭饮片中,黄柏内酯、黄柏酮的质量分数分别为3.164~6.483,0.281~1.614 mg·g~(-1)。结论:关黄柏饮片炒炭后,外观性状和内在成分变化明显,关黄柏饮片的质量标准难以应用于关黄柏炭。所购关黄柏炭饮片也因此难以做到炒炭程度统一,应根据关黄柏炒炭后的成分变化规律控制炒炭程度,进一步规范关黄柏和关黄柏炭饮片的质量标准。     

UPLC同时测定秦皮配方颗粒中7种成分

目的:建立UPLC同时测定秦皮配方颗粒中7种成分(秦皮甲素、毛柳苷、秦皮乙素、丁香苷、秦皮苷、秦皮素和东莨菪内酯)的方法,比较不同厂家及批次秦皮配方颗粒中7种成分含量的差异,为秦皮配方颗粒的科学质量控制提供依据。方法:采用Waters超高效液相色谱仪,Waters ACQUITY UPLC BEH C_(18)色谱柱(2.1 mm×50 mm,1.7μm),以甲醇(A)-0.1%磷酸水溶液(B)为流动相,梯度洗脱(0~1 min,5%~10%A;1~10 min,10%~12%A),流速0.4 m L·min~(-1),进样量2μL,柱温38℃,检测波长220 nm。结果:色谱峰纯度结果表明方法专属性良好。秦皮甲素、毛柳苷、秦皮乙素、丁香苷、秦皮苷、秦皮素和东莨菪内酯分别在各自范围内峰面积与浓度呈良好的线性关系;平均回收率分别为100.0%(RSD 2.0%),99.5%(RSD2.1%),99.9%(RSD 1.5%),99.7%(RSD 2.2%),99.4%(RSD 1.4%),100.8%(RSD 1.8%),99.4%(RSD 2.6%)。结论:该方法简便、准确,适用于秦皮配方颗粒中7种成分的同时定量测定,分析时间明显缩短,并对秦皮配方颗粒中除秦皮甲素和秦皮乙素之外的多种成分首次进行了定量测定,不同厂家及批次的秦皮配方颗粒主要成分含量存在一定的差异。     

桑白皮黄酮提取物对2型糖尿病大鼠非酒精性脂肪肝血管生成相关基因的影响

目的:初步探索桑白皮黄酮提取物对2型糖尿病大鼠非酒精性脂肪肝的治疗作用及机制研究。方法:将24只雄性大鼠随机分为3组,分别为正常组、模型组、桑白皮黄酮组(1.0 g·kg~(-1))。采用腹腔注射小剂量链脲佐菌素(streptozocin,STZ)结合高脂饲料喂养的方法,建立2型糖尿病伴非酒精性脂肪肝的模型,灌胃治疗16周时,观察比较桑白皮黄酮提取物对各组大鼠血清中空腹血糖(FBG),总胆固醇(TC),甘油三酯(TG),低密度脂蛋白胆固醇(LDL-C),糖耐量(OGTT)变化,油红O染色和苏木素-伊红(HE)染色观察肝脏病理改变,实时荧光定量聚合酶链式反应(Real-time PCR)检测肝脏血管内皮生长因子(vascular endothelial growth factor,VEGF),血小板衍生因子(platelet derived growth factor,PDGF)mRNA的表达。结果:灌胃干预16周后,与正常组比较,模型组大鼠FBG,TC,TG,LDL-C,含量均显著高于正常组(P0.05),应用桑白皮黄酮治疗后,上述生化指标较模型组均有显著下降(P0.05)。糖耐量试验显示模型组胰岛素敏感性下降,应用桑白皮黄酮治疗后胰岛素敏感性较模型组有显著改善。油红O染色结果显示模型组肝细胞胞浆内可见大量红染的脂肪滴,而桑白皮黄酮组肝细胞胞浆内未见红染的脂肪滴。HE染色结果显示模型组肝小叶中肝细胞发生明显的小泡样脂肪变性,部分肝细胞中脂滴融合成大的脂肪空泡,小叶中可见点状坏死,周围有炎性细胞浸润,而桑白皮黄酮组肝细胞结构正常。模型组肝脏中VEGF,PDGF mRNA表达量较正常组有显著升高,应用桑白皮黄酮治疗后,肝脏中VEGF,PDGF mRNA表达量明显降低(P0.05)。结论:桑白皮黄酮提取物对实验性2型糖尿病大鼠非酒精性脂肪性肝有一定的防治作用,其作用机制可能与抑制肝脏中VEGF,PDGF mRNA的表达有关。     

大黄、地榆、牡丹皮炒炭过程中热解反应机制的分析

目的:推断并验证大黄、地榆、牡丹皮3味中药炒炭的热解反应机制,进一步完善这3味中药炒炭研究的理论。方法:采用模式函数法中的单个扫描速率的不定温法(Coats-Redfern模型与Achar模型)推断大黄、地榆、牡丹皮3味中药炒炭过程中热解反应的机理函数,通过比较转化率(α)理论值、实验值与1/T的热分析曲线对机理函数进行验证。结果:积分形式表达式能更较好地描述大黄、地榆、牡丹皮3味中药炒炭热解的反应机制,三者的炒炭热解机理函数分别为9号机理函数积分形式g(α)=[(1-α)-1/3-1]2,2号机理函数积分形式g(α)=α+(1-α)ln(1-α),9号机理函数积分形式g(α)=[(1-α)-1/3-1]2。结论:3味中药炒炭的热解反应机制均属于反应扩散,转化率理论值与实验值存在一定的差异,运用热分析动力学方法只是尽可能地模拟这3味中药的炒炭热解反应过程。     

藏族药小檗皮不同药用部位中4种生物碱成分的HPLC含量测定

目的:建立同时测定藏族药小檗皮药材中木兰花碱、药根碱、巴马汀、小檗碱含量的方法,并比较茎内皮、茎木、茎栓皮、根内皮、根木和根栓皮中4种成分的差异。方法:采用HPLC法,应用Inert Sustain C18色谱柱(4.6 mm×250 mm,5μm),流动相乙腈-0.2%磷酸溶液,检测波长270 nm。结果:小檗皮不同部位之间的生物碱成分含量有明显的差异,根内皮及茎内皮中4种成分的含量明显高于茎木、茎栓皮、根木和根栓皮。此外,茎内皮比根内皮含有更多的木兰花碱,但小檗碱的含量明显低于根内皮,而两药用部位之间的总生物碱含量没有显著性差异。结论:该方法简便、准确、重复性好,可用于小檗皮药材的质量评控。从环境保护和可持续利用角度考虑,建议小檗皮药材取消根内皮而只以茎内皮入药。     

3种掩味剂单独或联合应用对黄柏的掩味作用探究及掩味前后化学成分的比较

目的:探讨三氯蔗糖、阿魏酸钠和β-环糊精单独或联合应用对黄柏水煎液的掩味效果,比较黄柏掩味前后的化学成分变化。方法:3种苦味抑制剂采用单独抑制苦味、两两联合抑制苦味、三者联合抑制苦味共计7种组合对黄柏水煎液进行掩味,考察掩味前后黄柏水煎液的苦度变化;利用HPLC建立掩味前后各样品液的指纹图谱,以共有峰相对峰面积、共有峰总面积为指标,分析其化学成分变化的程度与特点。结果:7种组合对黄柏水煎液均具有较好的抑苦作用。掩味剂联用后掩味效果更佳,优于单独使用,掩味后平均苦度均为Ⅰ级(不苦或几乎不苦)。指纹图谱共有峰有8个,掩味后7组供试品的56个峰中,除3个色谱峰在掩味前后相对峰面积具有显著性差异(但总变化率均10%)外,其余53个峰面积均无显著性差异;掩味前后黄柏的指纹图谱共有峰总面积无显著性差异。结论:3种掩味剂单独或联合应用对黄柏水煎液均具有较好的抑苦作用,且掩味前后对黄柏中化学成分的总量无显著影响。