黄芪甲苷Ⅳ预防肥胖性高血压的作用机制研究

目的 探讨黄芪甲苷Ⅳ(As Ⅳ)预防肥胖性高血压的作用机制.方法 将35只雄性Wistar大鼠分为正常脂肪饲料组(NC组,n=10)和高脂肪饲料组(n=25).16周后,将18只肥胖大鼠随机分为对照组(n=6)、As Ⅳ组(n=6)和As Ⅳ+α-bungaratoxin (α-BGT)组(n=6).测量各组干预前后体质量、血压,血浆和肾组织去甲肾上腺素(NE)水平.采用Western blot或实时荧光定量逆转录聚合酶链反应(RT-qPCR)检测各组下丘脑组织中瘦素受体(LepRb)、磷酸化信号转换器和转录激活因子-3(p-STAT3)、磷酸化磷脂酰肌醇3-激酶(p-PI3K)、细胞因子信号抑制因子(SOCS3)、酪氨酸磷酸酶(PTP1B)、皮质素原(POMC)、神经肽Y(NPY)水平.检测各组下丘脑和脂肪组织中α7烟碱乙酰胆碱受体(α7nAChR)、核因子κB激酶亚单位β/核因子κB抑制剂(IKKβ/NF-KB)和促炎细胞因子[白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)]的水平.结果 与对照组相比,AsⅣ组干预后葡萄糖不耐受和胰岛素抵抗指数(HOMA-IR)改善,甘油三酯(TG)、总胆固醇(TC)水平降低,差异有统计学意义(P＜0.05);连续干预6周后,对照组收缩压(SBP)、舒张压(DBP)、血浆和肾脏组织中NE水平升高,AsⅣ组SBP、DBP和NE水平降低,差异有统计学意义(P＜0.05);与NC组相比,对照组大鼠血浆瘦素水平升高,LepRb mRAN表达降低,瘦素信号分子p-STAT3的表达下降,p-PI3K、SOCS3 mRNA和PTP1B mRNA的表达增加,差异有统计学意义(P＜0.05).而As Ⅳ组p-STAT3、LepRb mRNA和POMC mRNA表达增加,p-PI3K、SOCS3 mRNA和PTP1B mRNA水平降低.与对照组比较,As Ⅳ组α7nAChR蛋白和mRNA表达升高,p-IKKβ、NF-KB蛋白及其mRNA表达降低,差异有统计学意义(P＜0.05).与As Ⅳ组比较,AsⅣ+α-BGT组α7nAChR阻断剂α-BGT降低了α7nAChR mRNA和蛋白表达水平,IKKβ mRNA、NF-KB mRNA、p-IKKβ、NF-KB、IL-1β和TNF-α蛋白水平均升高,差异有统计学意义(P＜0.05).与对照组和As Ⅳ+α-BGT组比较,As Ⅳ组α7nAChR mRNA表达升高,p-IKKβ、NF-KB、IL-1β、TNF-α表达降低,差异有统计学意义(P＜0.05).结论 AsⅣ可通过抑制炎症反应和改善瘦素抵抗有效预防肥胖相关高血压,AsⅣ的改善作用与α7nAchR表达增加密切相关.     

Controllable stripping of radiolabeled group in vivo to optimize nuclear imaging via NO-responsive bioorthogonal cleavage reaction

A novel “turn-off” strategy for controllable radionuclide clearance is established. 1,4-dihydropyridine (DHP) is used as a conditional linker to connect a radioisotope labeled moiety and nano-agent. A highly specific, sensitive and effective C–C bond cleavage of DHP happens in vivo when treated with nitric oxide which is provided by glyceryl trinitrate (GTN). The radioactive cut-off part from the nanoparticle is observed to be cleared quickly by microSPECT-CT. 3–5 times decreases of radioactivity in the blood, kidneys, intestine, heart and lungs are observed after GTN treatment in a biodistribution assay. The radioactivity redistribution indicates that the radioactive leaving part is indeed cut off and the radionuclide metabolism accelerated. Organ level internal dose assessment reveals the GTN treated groups carry only ½ the radiation dose of the control group. Collectively, a feasible pathway for controllable radionuclide clearance is for the first time provided for high contrast and low radiation nuclear imaging.

A novel “turn-off” strategy was developed for controllable radionuclide clearance in organisms.

Radiolabeled compounds with biological activity, or radiotracers, have been widely used for nuclear imaging and radiation therapy. Compared with other imaging modalities, a unique problem in radiotracer-based imaging is that the radioactivity cannot be simply “turned off”. As a result, it is impossible to carry out multi-scans of the same organ with different tracers in a short period. For instance, there are three kinds of marker receptors (ER, PR, HER2) expressed in breast cancer. Different type of breast cancer expresses a different combination of these three. Therefore, three kinds of radiotracers that aim to bind the corresponding receptors will be used to distinguish individual breast cancer phenotype. The uptake of a second tracer can''t be quantified accurately before the radioactivity of the first tracer decayed to background level, which may need one or two days depending on the half-life of radionuclide. So, it''s necessary to develop a strategy to “quench” the radioactivity. Furthermore, nonspecific binding is inevitable, and the “noise” or “background” from non-specific binding of radiotracers to non-target proteins cannot be easily differentiated from the specific binding component.Therefore, it''s meaningful to develop a kind of reaction that could strip the radiation by control. To achieve this goal, the metabolism of the radioactive part should be accelerated. The biorthogonal cleavage reaction would perfectly meet the needs, if (1) cleavable reactions could happen by the control in vivo; (2) the cut-off part has a relatively fast metabolism; (3) radionuclide is linked on the cut-off part.¹ One of the key issues that bio-orthogonal reactions resolve is to bind two components into one, and make the different metabolic rate of different components synchronized.² As the reaction in the opposite direction of bio-orthogonal reaction, the bio-orthogonal cleavage reaction can extinguish the radiation by diversifying the metabolism of radionuclides and the slow metabolic targeting components.Dihydropyridine (DHP) and its cleavage-triggering partner nitric oxide (NO) can perfectly meet the three conditions. NO, a hydrophobic signal molecule, could spread without any transmembrane transporter, which means NO could spread quickly and spend little energy.^3–5 Many kinds of NO donor drugs are commercially available, such as glyceryl trinitrate (GTN), sodium nitroprusside, etc. In our previous work,⁶ it was demonstrated that the physiological concentration of NO is high enough to cleave the C–C bond of DHP. Furthermore, NO donor drugs could offer a circumstance with higher NO concentration than normal physiological concentration. Therefore, it is possible for the reaction between DHP and NO from donor drugs to occur in vivo. Herein, a NO-triggerred “turn-off” system to extinguish the radiation by cleaving the radionuclides from nanoparticles is present. Benzyl group substituted 1,4-dihydropyridine can be cleaved through controlled NO stimulation by intraperitoneal injection of GTN.Nanoparticles as the major kind of theranostic agents have been developed quickly over these years.^7–11 During the process of synthesis, nanoparticles with similar shape, scale and dispersion properties would be obtained by manipulating conditions precisely. Therefore, the metabolism of nanoparticles in the living body is more predictable than diverse small molecules. Especially, radionuclides labeled nanoparticles not only play roles in diagnosis but also work well on tumor therapy. Enhanced permeability and retention (EPR) effect make nanoparticles wonderful radiotherapy reagents.^12–15 However, nanoparticles mean to be easily captured by the mononuclear phagocyte system (MPS), which makes the nanoparticles mostly enriched in liver besides in tumor.^16–20 Furthermore, metabolism of nanoparticles are quite slow than most of the small molecules, which means the radionuclides labeled on nanoparticles have similar slow metabolism to their carriers. Unnecessarily loaded radiation from the nanoparticles will also harm normal liver cells where the nanoparticles accumulate heavily.     

阿托伐他汀在缺血性卒中患者中的疗效研究

目的探讨阿托伐他汀对缺血性卒中患者的疗效。方法收集2012年6月~2014年2月来我院诊治的缺血性卒中患者311例为研究对象,依据其来诊的顺序随机分为实验组与对照组。两组均给予常规内科治疗,实验组加用阿托伐他汀治疗,治疗3个月后,观察两组的治疗效果。结果实验组的临床疗效明显高于对照组;治疗后实验组的总胆固醇、甘油三酯及低密度脂蛋白明显低于对照组,而高密度脂蛋白明显高于对照组。结论阿托伐他汀可以改善缺血性卒中患者血脂水平,提高缺血性卒中患者的治疗效果。     

组织工程骨血管生成的研究进展

目的对组织工程骨血管生成过程中种子细胞及相关细胞因子研究作一综述。方法广泛查阅近年来组织工程骨血管生成相关文献,对常见种子细胞来源、生物学特性、转变机制、相关细胞因子及信号通路等进行综述。结果随着显微外科技术、基因工程技术的发展,组织工程骨血管化细胞共培养体系的研究已有长足进展,无论是诱导性多能干细胞的引入,还是VEGF和血管生成素1双转染MSCs-内皮祖细胞共培养体系,均在骨生成和血管生成中显示出明显优势,但距临床应用仍有距离。结论采用基因修饰构建的种子细胞-细胞因子-支架材料复合物具有血管生成速度快、效率高、稳定性好的优势,在组织工程骨血管化中具有良好应用前景。     

临床护理路径在负压封闭引流治疗显微外科感染创面中的应用

目的：探讨临床护理路径的编制、实施及在显微外科感染创面负压封闭引流( VSD)治疗中的应用效果,规范VSD治疗的护理管理。方法选择2013年1—11月符合条件同意进行VSD治疗并实施临床护理路径的患者50例,为观察组;回顾性分析2012年1—12月行VSD治疗并实施常规护理的50例患者,为对照组,通过查阅电子病历和VSD治疗记录,收集临床数据进行对比分析。对VSD治疗期间患者的健康知识、自身责任感、健康责任等指标进行评价,完善和论证临床护理路径。结果观察组患者的健康知识、自我责任感、健康责任、压力处理、患者满意度得分分别为(55.47±4.41),(25.53±1.60),(26.12±2.21),(23.96±2.14),(3.80±0.39)分,均高于对照组,差异有统计学意义(P<0.01)。结论“临床护理路径适合VSD治疗显微外科感染创面患者的护理,能为患者提供优质护理服务,提高患者满意度,并取得了良好的经济效益和社会效益,对护理过程管理具有指导意义,值得在临床推广应用。