血管紧张素Ⅱ和血管紧张素转换酶2在1型和2型糖尿病小鼠胰腺中的表达差异

目的探讨血管紧张素II(ATⅡ)和血管紧张素转换酶2(ACE2)在1型糖尿病(T1DM)和2型糖尿病(T2DM)小鼠胰腺组织表达的差异。方法取12周和24周正常雄性C57bl/6小鼠、非肥胖T1DM NOD小鼠和自发T2DM db/db小鼠胰腺组织,分别进行免疫组化和Western-blot研究。观察ATⅡ和ACE2蛋白的表达。结果 12、24周龄db/db小鼠ATⅡ蛋白表达均明显升高(P0.01)。12周龄NOD小鼠胰腺ACE2表达升高(P0.01),而24周龄时出现下降;db/db小鼠ACE2与之相反。结论胰腺组织中,T1DM早期以ACE2升高为主而ATⅡ表达不明显,而T2DM存在明显的ATⅡ表达升高,且晚期可出现ACE2表达上升。     

血管紧张素II和血管紧张素转换酶2在1型和2型糖尿病小鼠胰腺中的表达差异

目的 探讨血管紧张素Ⅱ(ATⅡ)和血管紧张素转换酶2(ACE2) 在1型糖尿病(T1DM)和2型糖尿病(T2DM)小鼠胰腺组织表达的差异. 方法 取12周和24周正常雄性C57bl/6小鼠、非肥胖T1DM NOD小鼠和自发T2DM db/db小鼠胰腺组织,分别进行免疫组化和Western-blot研究.观察ATⅡ和ACE2蛋白的表达. 结果 12、24周龄db/db小鼠ATⅡ蛋白表达均明显升高(P<0.01).12周龄NOD小鼠胰腺ACE2表达升高(P<0.01),而24周龄时出现下降;db/db小鼠ACE2与之相反. 结论 胰腺组织中,T1DM早期以ACE2升高为主而ATⅡ表达不明显,而T2DM存在明显的ATⅡ表达升高,且晚期可出现ACE2表达上升.     

自然杀伤T细胞在血管紧张素Ⅱ诱导的高血压中的作用

目的:通过构建Ang Ⅱ诱导的小鼠高血压模型,研究自然杀伤T细胞(NKT)的作用。方法:在CD1d基因敲除小鼠及野生对照小鼠中,采用缓释泵持续灌注血管紧张素Ⅱ(Ang Ⅱ)490ng·kg~(-1)·min~(-1),14 d建立小鼠高血压模型,尾动脉无创性血压测量方法监测小鼠血压的变化;HE染色观察小鼠主动脉壁厚度的变化;Masson染色观察主动脉血管纤维化的程度;实时荧光定量PCR检测血管组织中IL-6及TNF-α的表达;流式分析检测血管壁巨噬细胞的浸润。结果:与对照组相比,Ang Ⅱ灌注14 d明显升高小鼠的收缩压、血管壁的厚度及纤维化程度、血管组织的炎症因子IL-1β及TNF-αmRNA的表达及血管组织中巨噬细胞的浸润;重要的是,CD1d基因的敲除进一步加重以上变化。结论:自然杀伤T细胞通过减轻巨噬细胞的浸润拮抗了血管紧张素Ⅱ灌注引起的血压升高。     

Irisin对2型糖尿病小鼠血糖的影响及机制

目的:研究Irisin对2型糖尿病(type 2 diabetes mellitus,T2DM)小鼠血糖的影响及机制。方法:采用喂养高脂饮食结合腹腔注射小剂量的链脲佐菌素(STZ)建立T2DM小鼠模型。Western blot检测Irisin经腹腔注射后的血浆水平。血糖仪检测T2DM小鼠经腹腔注射Irisin后30、60、90、120、150、180和210 min的血糖水平。Western blot检测注射Irisin后肝脏组织中葡萄糖-6-磷酸酶(G6pase)和磷酸烯醇式丙酮酸羧化酶(PEPCK)的表达。结果:1与正常饮食(ND)组相比,高脂饮食(HD)组小鼠在第6周时血糖糖水平明显增加(P0.05),且葡萄糖耐量降低,说明T2DM小鼠造模成功。2与对照(Control)组相比,Control+Irisin组血浆中的Irisin蛋白水平明显升高(P0.05)。3与T2DM+Vehicle(生理盐水)组相比,T2DM+Irisin组血糖于30 min时开始降低,60 min时出现显著差异(P0.05),到120 min时下降到最低点,以后逐渐升高。4与Control组相比,T2DM组G6pase和PEPCK的水平升高(P0.05),经外源给予Irisin后,G6pase和PEPCK的水平下降(P0.01)。结论:Irisin对T2DM小鼠具有降低血糖的作用,这可能与降低T2DM小鼠肝脏糖异生有关。     

血管紧张素转换酶基因多态性与2型糖尿病患者下肢血管病变的相关性

正该文探讨血管紧张素转换酶(angiotensin converting enzyme,ACE)基因插入/缺失(I/D)位点多态性与2型糖尿病(type 2diabetes mellitus,T2DM)患者下肢血管病变(lower extremity atherosclerosis,LEA)的相关性。方法:以2015年6月至2016年3月期间在华北理工大学附属医院住院并已确诊的T2DM患者为研究对象,分为T2DM无LEA组(120例)和T2DM并发LEA组(260例),采用彩色多普勒超声检测糖尿病     

E-选择素基因A561C多态性与糖尿病并发冠心病的关系

目的 :探讨E 选择素基因A5 6 1C多态性与 2型糖尿病 (T2 DM)并发冠心病 (CHD)的关系。方法 :用聚合酶链反应 限制性片段长度多态性 (PCR RFLP)方法探查E 选择素基因A5 6 1C多态性在对照组、CHD组、T2 DM组、T2 DM并发CHD组中的基因频率分布。结果 :CHD组、T2 DM并发CHD组E 选择素的C等位基因频率明显高于对照组 (P <0 .0 5 ) ,不同基因型间血浆E 选择素水平差异有显著意义 (P <0 .0 1)。结论 :E 选择素基因A5 6 1C多态性与CHD及T2 DM并发CHD的发生有关     

白黎芦醇减轻Ⅱ型糖尿病小鼠心肌缺血/再灌注损伤的作用

目的:探讨白黎芦醇(RSV)减轻Ⅱ型糖尿病(T2DM)小鼠心肌缺血/再灌注损伤(MI/RI)的作用及其机制。方法: 采用喂养高脂饮食结合小剂量链脲佐菌素(STZ)建立T2DM小鼠模型。造模成功后立即给予RSV(10mg/kg)每日1次灌胃,连续3周。实验分为正常假手术组、正常手术对照组、DM假手术组、DM手术对照组、RSV组、CpC组,每组20只。手术方式采用心脏冠状动脉左前降支结扎30 min、再灌注3 h或24 h。抑制剂组于术前1 h腹腔注射Compound C（20 mg/kg）。用TTC染色法检测心肌梗死(MI)面积,TUNEL法检测心肌细胞凋亡,ELISA法检测caspase-3活性、血浆脂联素（APN）水平,Western blot法检测AMPK、p-AMPK及脂肪组织APN的含量。结果: 喂养高脂饮食结合小剂量STZ能够成功建立T2DM小鼠模型。与DM手术对照组相比,RSV饲喂能够减轻T2DM小鼠MI/RI,减小MI面积、减少心肌细胞凋亡（P<0.01）,降低caspase-3的活性（P<0.05）。RSV还能够上调脂肪组织APN表达,逆转T2DM小鼠低APN血症（P<0.01）。AMPK抑制剂Compound C可显著减弱RSV的心肌保护作用（P<0.05）。结论: RSV可通过逆转T2DM小鼠的低脂联素血症,在MI/RI时发挥对心肌的保护作用。     

苯那普利与伊贝沙坦联用对2型糖尿病患者早期糖尿病肾病的影响

血管紧张素转换酶抑制剂 (ACEI)与血管紧张素Ⅱ 1型受体拮抗剂 (ARB)能减少糖尿病患者尿白蛋白排泄及延缓肾损害的进展。本研究旨在评估长期 (平均 2年 )苯那普利、伊贝沙坦及其联用对 2型糖尿病 (T2DM )早期糖尿病肾病(DN)进展的影响。一、对象与方法1 对象 :病例来自“社区居     

血管紧张素Ⅱ、血管紧张素(1-7)对NIT-1细胞胰岛素信号通路的影响

目的 研究血管紧张素Ⅱ、血管紧张素(1-7)对胰岛β细胞胰岛素信号通路的影响.方法 小鼠胰岛β细胞株NIT-1予(1)0、10-7、10-6、10-5和10-4 mol/L浓度血管紧张素Ⅱ处理24h;(2)0、10-7、10-6、10-5和10-4mol/L浓度血管紧张素(1-7)处理24h;(3)血管紧张素Ⅱ、血管紧张素(1-7)联合处理24h,分为对照、10-5 mol/L血管紧张素Ⅱ、10-6 mol/L血管紧张素(1-7)、10-5 mol/L血管紧张素Ⅱ+10-6 mol/L血管紧张素(1-7)组.Western印迹检测胰岛素受体β亚基酪氨酸磷酸化(IR-β-Tyr)及蛋白激酶β丝氨酸磷酸化(Akt-Ser)水平.结果 血管紧张素Ⅱ浓度10-5和10-4mol/L时,胰岛素刺激的IR-β-Tyr、Akt-Ser表达显著降低;不同浓度血管紧张素(1-7)作用下,胰岛素刺激的IR-β-Tyr、Akt-Ser表达与对照组相比无差异;加入血管紧张素(1-7)共同孵育可逆转血管紧张素Ⅱ对Akt-Ser表达的抑制,而血管紧张素Ⅱ对IR-β-Tyr表达的抑制无效应.结论 在β细胞中,血管紧张素Ⅱ抑制胰岛素信号传导,血管紧张素(1-7)可拮抗血管紧张素Ⅱ对胰岛素刺激的Akt-Ser的抑制.     

细胞焦亡在血管紧张素Ⅱ诱导的腹主动脉瘤形成中的作用研究

目的 分析细胞焦亡在血管紧张素Ⅱ诱导的腹主动脉瘤(AAA)发生和发展中的作用.方法 2019年9月至2021年9月,将50只C57BL/6雄性野生型小鼠按照抽签法随机分为对照组(n=24)和血管紧张素Ⅱ组(n=26),所有小鼠在肩胛骨中部皮下植入渗透微型泵注入0.9％氯化钠溶液(对照组)或血管紧张素Ⅱ(血管紧张素Ⅱ组)...     

妊娠时间与肺结核复发的相关性研究及诊治对策

目的 分析肺结核史患者妊娠时间和肺结核复发间相关性.方法 选取我院收治的有肺结核史的妊娠妇女576例作为研究对象,对其妊娠前肺结核治疗、治愈后妊娠时间、妊娠后复发肺结核等进行分析,总结有肺结核史育龄女性的妊娠时间和肺结核复发之间的关系.结果 肺结核治愈后不同时间段妊娠者的结核复发率比较,差异具有显著性（P＜0.05）,停药后间隔时间越久妊娠,肺结核复发的几率越小.结论 加强孕期痰菌检查,及早发现复发肺结核,提高母婴安全.     

我国骨关节结核诊治的回顾与展望

骨关节结核是危害人们健康的严重感染性疾病,近95％由他处结核病继发而来.罹患骨关节结核疾病后几乎均将致残,严重影响人们的健康、工作和生活.建国以来在党和国家的关心和支持下,骨关节结核的诊治水平取得了长足进步.时至今日,由于多种原因,学科发展和被重视程度受到一定的制约,同整个医疗行业的发展不相适应.回顾过去,展望未来,我们需要重新审视骨关节结核的诊治方法,努力推进骨关节结核诊疗技术的科学发展.     

Effect of phosphorylation of MAPK and Stat3 and expression of c-fos and c-jun proteins on hepatocarcinogenesis and their clinical significance

AIM To study the effect of phosphorylation ofMAPK and Stat3 and the expression of c-fos andc-jun proteins on hepatocellular carcinogenesisand their clinical significance.METHODS SP immunohistochemistry was usedto detect the expression of p42/44~(MAPK), p-Stat3,c-fos and c-jun proteins in 55 hepatocellularcarcinomas (HCC) and their surrounding livertissues.RESULTS The positive rates and expressionlevels of p42/44~(MAPK), p-Stat3, c-fos and c-junproteins in HCCs were significantly higher thanthose in pericarcinomatous liver tissues (PCLT).A positive correlation was observed between theexpression of p42/44~(MAPK) and c-fos proteins, andbetween p-Stat3 and c-jun, but there was nosignificant correlation between P42/44~(MAPK) and p-Stat3 in HCCs and their surrounding livertissues.CONCLUSION The abnormalities of Ras/Raf/MAPK and JAKs/ Stat3 cascade reaction maycontribute to malignant transformation ofhepatocytes. Hepatocytes which are positive forp42/ 44~(MAPK), c-fos or c-jun proteins may bepotential malignant pre-cancerous cells.Activation of MAPK and Stat3 proteins may be anearly event in hepatocellular carcinogenesis.     

Overweight and Obesity and Progression of ADPKD

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Replication and Inhibitors of Enteroviruses and Parechoviruses

The Enterovirus (EV) and Parechovirus genera of the picornavirus family include many important human pathogens, including poliovirus, rhinovirus, EV-A71, EV-D68, and human parechoviruses (HPeV). They cause a wide variety of diseases, ranging from a simple common cold to life-threatening diseases such as encephalitis and myocarditis. At the moment, no antiviral therapy is available against these viruses and it is not feasible to develop vaccines against all EVs and HPeVs due to the great number of serotypes. Therefore, a lot of effort is being invested in the development of antiviral drugs. Both viral proteins and host proteins essential for virus replication can be used as targets for virus inhibitors. As such, a good understanding of the complex process of virus replication is pivotal in the design of antiviral strategies goes hand in hand with a good understanding of the complex process of virus replication. In this review, we will give an overview of the current state of knowledge of EV and HPeV replication and how this can be inhibited by small-molecule inhibitors.     

Effects of sex and time of day on metabolism and excretion of corticosterone in urine and feces of mice

Non-invasive techniques to monitor stress hormones in small animals like mice offer several advantages and are highly demanded in laboratory as well as in field research. Since knowledge about the species-specific metabolism and excretion of glucocorticoids is essential to develop such a technique, we conducted radiometabolism studies in mice (Mus musculus f. domesticus, strain C57BL/6J). Each mouse was injected intraperitoneally with 740 kBq of 3H-labelled corticosterone and all voided urine and fecal samples were collected for five days. In a first experiment 16 animals (eight of each sex) received the injection at 9 a.m., while eight mice (four of each sex) were injected at 9 p.m. in a second experiment. In both experiments radioactive metabolites were recovered predominantly in the feces, although males excreted significantly higher proportions via the feces (about 73%) than females (about 53%). Peak radioactivity in the urine was detected within about 2h after injection, while in the feces peak concentrations were observed later (depending on the time of injection: about 10h postinjection in experiment 1 and about 4h postinjection in experiment 2, thus proving an effect of the time of day). The number and relative abundance of fecal [3H]corticosterone metabolites was determined by high performance liquid chromatography (HPLC). The HPLC separations revealed that corticosterone was extensively metabolized mainly to more polar substances. Regarding the types of metabolites formed, significant differences were found between males and females, but not between the experiments. Additionally, the immunoreactivity of these metabolites was assessed by screening the HPLC fractions with four enzyme immunoassays (EIA). However, only a newly established EIA for 5alpha-pregnane-3beta,11beta,21-triol-20-one (measuring corticosterone metabolites with a 5alpha-3beta,11beta-diol structure) detected several peaks of radioactive metabolites with high intensity in both sexes, while the other EIAs showed only minor immunoreactivity. Thus, our study for the first time provides substantial information about metabolism and excretion of corticosterone in urine and feces of mice and is the first demonstrating a significant impact of the animals' sex and the time of day. Based on these data it should be possible to monitor adrenocortical activity non-invasively in this species by measuring fecal corticosterone metabolites with the newly developed EIA. Since mice are extensively used in research world-wide, this could open new perspectives in various fields from ecology to behavioral endocrinology.     

Effect of phosphorylation of MAPK and Stat3 and expression of c-fas and c-jun proteins on hepatocarcinogenesis and their clinical significance

AIM To study the effect of phosphorylation ofMAPK and Stat3 and the expression of c-fos andc-jun proteins on hepatocellular carcinogenesisand their clinical significance.METHODS SP immunohistochemistry was usedto detect the expression of p42/44MAPK, p-Stat3,c-fos and c-jun proteins in 55 hepatocellularcarcinomas (HCC) and their surrounding livertissues.RESULTS The positive rates and expressionlevels of p42/44MAPK, p-Stat3, c-fos and c-junproteins in HCCs were significantly higher thanthose in pericarcinomatous liver tissues (PCLT).A positive correlation was observed between theexpression of p42/44MAPK and c-fos proteins, andbetween p-Stat3 and c-jun, but there was nosignificant correlation between p42/44MAPK and p-Stat3 in HCCs and their surrounding livertissues.CONCLUSION The abnormalities of Ras/Rat/MAPK and JAKs/ Stat3 cascade reaction maycontribute to malignant transformation ofhepatocytes. Hepatocytes which are positive forp42/ 44MAPK, c-fos or c-jun proteins may bepotential malignant pre-cancerous cells.Activation of MAPK and Stat3 proteins may be anearly event in hepatocellular carcinogenesis.     

心电图、心电向量图与冠状动脉造影结果对比分析

目的:通过分析心电图(Electrocardiogram,ECG)和心电向量图(Vectorcardiogram,VCG)的改变与冠脉造影（CAG）结果进行对比,探讨ECG、VCG在冠状动脉病变中的诊断价值。方法: 选择2008年1月~2009年12月临床拟诊断为冠心病患者108例,行常规ECG、VCG检查,并于1周内进行CAG,对检查结果依据各自的诊断标准进行判定,以CAG为标准诊断法,利用四格表法,计算相关评价真实性的指标并进行比较。结果: ①VCG检测的灵敏度、特异度、准确度显著高于ECG(P<0.05,P<0．01)。②ECG、VCG阳性率与冠脉病变支数组间比较:在单支病变、双支病变中,VCG阳性率明显高于ECG(P<0.05),左主干或三支病变无统计学意义;组内比较:ECG组左主干或三支病变组较单支病变、双支病变阳性率高(P<0.05,P<0.01);VCG组左主干或三支病变组较单支病变阳性率高(P<0.05);与双支病变阳性率比较无统计学意义;③ECG、VCG阳性率与冠脉病变程度组间比较:冠脉病变狭窄50%～69%的VCG阳性率明显高于ECG (P<0.05),其他两组阳性率比较无统计学意义;组内比较:ECG组冠脉病变狭窄≥90%较50%～69%、70%～89%的阳性率高(P<0.05,P<0.01); VCG组狭窄≥90%较50%～69%阳性率高（P<0.01),其他无统计学意义。结论: VCG对冠心病检测价值显著高于ECG。     

Detection and characterization of the product of hydroethidine and intracellular superoxide by HPLC and limitations of fluorescence

Here we report the structural characterization of the product formed from the reaction between hydroethidine (HE) and superoxide (O(2)(.-)). By using mass spectral and NMR techniques, the chemical structure of this product was determined as 2-hydroxyethidium (2-OH-E(+)). By using an authentic standard, we developed an HPLC approach to detect and quantitate the reaction product of HE and O(2)(.-) formed in bovine aortic endothelial cells after treatment with menadione or antimycin A to induce intracellular reactive oxygen species. Concomitantly, we used a spin trap, 5-tert-butoxycarbonyl-5-methyl-1-pyrroline N-oxide (BMPO), to detect and identify the structure of reactive oxygen species formed. BMPO trapped the O(2)(.-) that formed extracellularly and was detected as the BMPO-OH adduct during use of the EPR technique. BMPO, being cell-permeable, inhibited the intracellular formation of 2-OH-E(+). However, the intracellular BMPO spin adduct was not detected. The definitive characterization of the reaction product of O(2)(.-) with HE described here forms the basis of an unambiguous assay for intracellular detection and quantitation of O(2)(.-). Analysis of the fluorescence characteristics of ethidium (E(+)) and 2-OH-E(+) strongly suggests that the currently available fluorescence methodology is not suitable for quantitating intracellular O(2)(.-). We conclude that the HPLC/fluorescence assay using HE as a probe is more suitable [corrected] for detecting intracellular O(2)(.-).     

大鼠骨髓间充质干细胞的分离培养和外源基因的导入

目的探讨绿色荧光蛋白基因转染骨髓间质干细胞的可行性。方法采用F icoll-PaqueTMP lus淋巴细胞分离液,根据细胞密度梯度原理,分离大鼠骨髓间充质干细胞(rM SC s)并进行体外原代培养和传代扩增,倒置相差显微镜观察细胞生长情况,免疫细胞化学法对其初步鉴定。流式细胞仪分析转染效率。结果原代和传代培养的细胞呈现梭形外观,具有较强的生长增殖能力;细胞均一表达CD44、CD54、CD106、CD29抗原。电穿孔法转染rM SC s转染率为32.8%±3%。结论采用比重为1.077 g/L的F icoll-PaqueTMP lus能分离获得大鼠骨髓间充质干细胞,经原代培养和传代培养能够迅速扩增。电穿孔法具有较高的介导外源基因表达于rM SC s的效率。