自发性高血压大鼠血管壁肌球蛋白轻链磷酸酶含量的研究

目的：肌球蛋白轻链磷酸酶（MLCP）水平与血管的收缩与舒张功能有着重要的关系。本研究探讨MLCP与自发性高血压大鼠（SHR）高血压发病机制之间的关系。方法：在摄氏4度的环境下，取SHR与正常血压WKY大鼠各10只断头处死，迅速取其大动脉，称重速冻后将血管磨成匀浆，置于缓冲液中，并通过离心提取蛋白质，校正两组总蛋白的浓度后，分别应用（SDS-PAGE）、Western印迹杂交和化学发光方法测定SHR与WKY大鼠动脉血管壁MLCP的130kD、38kD、21kD三个亚单位的含量，对显影结果进一步进行吸光度扫描分析。并进行两组间的比较。结果：SHR的MLCP130kD亚单位的含量明显高于WKY大鼠（P〈0．01），而38kD和21kD亚单位含量则明显低于WKY大鼠（P〈0．01）。结论：SHR和WKY大鼠血管壁MLCP的130kD、38kD、21kD三个亚单位含量有着明显的差异，提示MLCP结构或功能的异常可能与SHR高血压的发病有关。     

全反式维甲酸对高血压大鼠心脏氧化应激水平的影响

目的:探讨全反式维甲酸(atRA)对高血压心脏还原型辅酶I氧化酶P22亚单位(p22phox)表达以及氧化应激水平的影响。方法:采用12周龄雄性自发性高血压大鼠(SHR)及其同源对照WKY大鼠,经腹腔注射at-RA,为期1月。分别采用免疫印迹、硫代巴比妥酸比色以及透射电镜技术测定atRA治疗后SHR心脏p22phox的表达、丙二醛(MDA)含量以及心肌超微结构情况。结果:与WKY对照组相比,SHR心脏组织中p22phox蛋白表达与MDA含量明显升高(P均<0.01)。而atRA治疗后SHR(低、高剂量atRA组)大鼠心脏组织中p22phox蛋白表达与MDA水平出现下调(P均<0.05),同时伴有心肌损伤减轻。结论:长期atRA治疗可降低SHR大鼠心脏组织中p22phox表达与MDA水平,提示atRA在高血压病中具有一定的抗氧化效应。     

自发性高血压大鼠肾上腺髓质素含量与中性内肽酶分布的关系

目的测定自发性高血压大鼠(SHR) 与WKY大鼠组织肾上腺髓质素(ADM)含量和中性内肽酶(NEP)活性及其表达水平,以探讨NEP的变化在高血压时组织ADM水平升高中的意义.方法采用放射免疫分析方法和荧光分光光度法分别检测血浆和组织的ADM含量和NEP的活性,同时用半定量RT-PCR和免疫组织化学染色法分别检测组织NEP mRNA和NEP蛋白的表达和分布.结果 ADM和NEP广泛分布于大鼠的血浆和组织,SHR的ADM含量在各组织普遍高于WKY大鼠.SHR心脏和小肠NEP的活性和mRNA表达均显著低于WKY大鼠,ADM含量与NEP活性呈负相关.反之,SHR血浆和肾脏NEP活性、肾脏NEP mRNA水平与蛋白量均高于WKY大鼠,ADM含量与NEP活性呈正相关.在肺脏和主动脉,NEP的活性无明显变化.结论 NEP在自发性高血压大鼠各组织器官中的变化与ADM含量的变化不一致,提示高血压时组织局部的NEP对ADM含量的影响不同.     

全反式维甲酸对高血压大鼠体内apelin-APJ信号系统的影响

目的:探讨全反式维甲酸(atRA)对高血压大鼠体内心血管活性多肽apelin及其受体APJ信号的影响。方法:采用12周龄雄性自发性高血压大鼠(SHR)及其同源对照WKY大鼠,经腹腔注射atRA,为期1月。分别用实时荧光定量多聚酶链式反应(PCR)与免疫印迹技术测定atRA治疗后SHR体内apelin和APJ受体的表达情况。结果:与WKY对照组相比,SHR心脏组织中apelin及其受体APJ的 mRNA和蛋白表达明显下调(P均<0.01)。而atRA治疗后SHR(低、高剂量atRA组)大鼠心脏组织中apelin、APJ表达出现上调(P均<0.05)。结论:长期atRA治疗促进SHR大鼠心脏组织中apelin及其受体APJ的表达增加,提示转录调节剂atRA很可能对人类高血压病防治具有积极作用。     

自发性高血压大鼠肾上腺髓质素含量与中性内肽酶分布的关系

目的 测定自发性高血压大鼠(SHR)与WKY大鼠组织肾上腺髓质素(ADM)含量和中性内肽酶(NEP)活性及其表达水平，以探讨NEP的变化在高血压时组织ADM水平升高中的意义。方法 采用放射免疫分析方法和荧光分光光度法分别检测血浆和组织的ADM含量和NEP的活性，同时用半定量RT-PCR和免疫组织化学染色法分别检测组织NEP mRNA和NEP蛋白的表达和分布。结果 ADM和NEP广泛分布于大鼠的血浆和组织，SHR的ADM含量在各组织普遍高于WKY大鼠。SHR心脏和小肠NEP的活性和mRNA表达均显著低于WKY大鼠，ADM含量与NEP活性呈负相关。反之，SHR血浆和肾脏NEP活性、肾脏NEP mRNA水平与蛋白量均高于WKY大鼠，ADM含量与NEP活性呈正相关。在肺脏和主动脉，NEP的活性无明显变化。结论 NEP在自发性高血压大鼠各组织器官中的变化与ADM含量的变化不一致，提示高血压时组织局部的NEP对ADM含量的影响不同。     

桑杞清眩颗粒干预自发性高血压大鼠心肌细胞凋亡的实验研究

目的观察桑杞清眩颗粒对高血压心肌重构的抑制作用及其可能机制。方法选8只4周龄雄性WKY大鼠和16只4周龄雄性自发性高血压(SHR)大鼠,WKY大鼠作为对照组(WKY),SHR大鼠随机分为模型组(SHR组)和给药组(SQ+SHR组),每组8只。每组在治疗16周后处死大鼠,尾套法测量SHR尾动脉收缩压、舒张压、平均压,计算心脏重量指数;用脱氧核苷酸末端转移酶介导的缺口末端标记法(TUNEL)染色来检测凋亡心肌细胞;用蛋白免疫印迹法检测大鼠心肌组织中B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、活化型半胱天冬酶-3(cleaved Caspase-3)。结果与WKY组相比,桑杞清眩颗粒显著抑制SHR大鼠收缩压的升高、心脏重量指数的增加、抑制高血压引起的大鼠心肌细胞凋亡、Bcl-2的降低及Bax和cleaved Caspase-3的增加。结论桑杞清眩颗粒可以抑制SHR大鼠血压升高,减轻心肌肥厚,其作用机制可能与抑制自发性高血压大鼠心肌细胞凋亡有关。     

自发性高血压大鼠发病机制及与血管内皮生长因子和成纤维细胞生长因子关系的实验研究

目的探讨血管内皮生长因子(VEGF)和成纤维细胞生长因子(FGF)是否参与自发性高血压大鼠(SHR)高血压的发生及其与靶器官心脏损害的关系。方法将20只雄性SHR分为SHR模型组和氨氯地平10 mg/(kg·d)喂养的模型对照组,每组10只;另取10只WKY作为正常对照组。共喂养12周,每周测量1次血压。于12周实验结束时,先采集3组大鼠全血2 mL,并分离血浆进行VEGF和FGF的ELISA检测;再获取3组大鼠心脏组织,进行实时荧光定量检测VEGF和FGF的基因表达和Western Blot检测二者蛋白的表达。结果 SHR进行氨氯地平喂养后,血压明显下降,与SHR模型组比较差异有统计学意义(P0.05),而与WKY正常对照组比较差异无统计学意义(P0.05);ELISA检测发现,SHR模型组VEGF和FGF的表达较WKY正常对照组和氨氯地平模型对照组升高(P0.05);荧光定量检测发现SHR模型组VEGF和FGFmRNA较氨氯地平模型对照组与WKY正常对照组的表达明显增加(P0.05);而SHR模型组VEGF和FGF蛋白水平表达较氨氯地平模型对照组与WKY正常对照组明显增加(P0.05)。结论 VEGF和FGF参与了SHR靶器官心脏的损害,可能在高血压的发展中扮演着重要角色。     

内皮型一氧化氮合酶基因导入对高血压大鼠细胞凋亡的影响

目的研究内皮型一氧化氮合酶(eNOS)基因导入对高血压大鼠心脏、肾脏细胞凋亡的影响。方法将实验大鼠分为自发性高血压大鼠(SHR)组、AAV-LacZ组和AAV-eNOS组,每组8只,另设8只正常血压(WKY)大鼠为WKY组。AAV-eNOS组经尾静脉注射AAV-eNOS 200μl(含eNOS基因拷贝1×1012),AAV-LacZ组注射AAV-LacZ 200μl,WKY及SHR组大鼠分别经尾静脉给予等量0.1 mol/L PBS。应用原位末端标记(TUNEL)法检测各组大鼠心、肾组织中的细胞凋亡,免疫组织化学方法检测eNOS的表达。结果①SHR组大鼠心肌组织及肾脏组织染色阳性信号明显增多,与WKY组比较具有显著性差异(P<0.05),AAV-eNOS组凋亡阳性信号明显低于SHR组,差异显著(P<0.05)。②SHR组及AAV-LacZ组大鼠心肌组织eNOS表达低于WKY组,差异具有显著性(P<0.05);与SHR组大鼠比较,AAV-eNOS组eNOS表达明显增加,差异具有显著性(P<0.05)。各组大鼠肾脏eNOS蛋白表达未见明显差异。结论 eNOS基因导入可明显抑制心肌及肾脏组织细胞的凋亡,保护靶器官。     

心肌组织和血浆IGF—Ⅰ的相关性

本研究采用放射免疫分析法测定自发性高血压大鼠(SHR)和正常血压的Witar-Kyoto大鼠(WKY)血浆和心肌组织中的IGF-Ⅰ水平,以心脏湿重(HW)和心脏湿重/体重(HW/BW)来判定心肌肥厚.结果显示:SHR的HW较WKY有显著升高(P<0.05),HW/BM则较WKY有高度显著升高(P<0.01).两组大鼠心肌组织中IGF-Ⅰ与血浆中的IGF-Ⅰ显示正相关(WKY:r=0.8485 P<0.05;SHR:r=0.9529(P<0.005).试验结果提示不论心脏生理和病理情况下,心脏合成和分泌的IGF-Ⅰ对循环中的IGF-Ⅰ水平均有影响,而在心肌肥厚,心肌组织中的IGF-Ⅰ病理水平增高时,影响更为明显.     

自发性高血压大鼠心脏重构与ACE2 mRNA的表达

目的:观察不同月龄的自发性高血压大鼠(SHR)的心脏血管紧张素转换酶2(ACE2)mRNA表达水平,探讨心脏重构与ACE2的内在联系。方法:将12周龄雄性SHR 18只和12周龄WKY Wistar-Kyoto rats大鼠18只随机分为两组,从WKY大鼠组和SHR组中各抽取9只处死,剩余的9只再喂养12周后处死。测量大鼠心脏的质量(HW)与体质量(BW)并计算HW/BW的比值。以实时定量RT-PCR法检测ACE2 mRNA的表达。结果:①与同周龄WKY大鼠组比较,SHR组HW/BW的比值显著增加(P0.01);与12周龄SHR组比较,24周龄SHR组的HW/BW显著增加(P0.05)。②与同周龄的WKY大鼠组比较,SHR组ACE2 mRNA的表达显著降低(P0.01);与12周龄的SHR组比较,24周龄的SHR组ACE2 mRNA的表达显著降低(P0.01)。结论:自发性高血压大鼠心脏重构伴随着心脏中ACE2 mRNA的表达下调。     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

124例耐多药结核分枝杆菌基因突变特征分析

目的对临床分离的耐多药结核分枝杆菌相关基因的突变特征进行分析。方法对124例耐多药结核分枝杆菌以及50株敏感株的耐药相关基因(包括异烟肼inh A、kat G、oxyR-ahp C间隔区以及利福平rpo B)进行序列测定,分析其基因突变情况。结果异烟肼耐药inh A基因突变率为14.5%;kat G基因突变率为70.2%(87/124),主要位于315位;oxyR-ahp C间隔区突变率为15.3%;inh A、kat G两种基因同时突变率75.0%,三种基因同时突变率为89.5%。利福平rpo B基因突变的检出率高达95.2%,突变主要发生在531、526、516位点。结论我省耐多药菌异烟肼耐药相关基因最常见突变为kat G 315、inh A C-T(-15)、axyR-ahp C间隔区(-10)C-T,利福平为rpo B531、526、516。结合MDR-TB耐药相关基因的特征分析,可以建立一种快速、准确、特异的适合于我省的检测结核菌耐多药性的新方法。     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

治疗高血压药物的经济学评价

重视高血压治疗中的经济学评价,对利用我国有限的卫生资源来遏制高血压对人民群众的危害有着重要的现实意义。药物经济学对于药物治疗的成本和治疗的结果给予同样的关注。因为治疗高血压的费用,不仅涉及药物价格,还包括患者的危险水平,降压疗效和对临床终点事件的影响,以及治疗的依从性和安全性。因此药物经济学更强调整体成本和价-效比。低危病人,若非药价低廉,治疗的价-效比不够理想。而在高危的患者,价-效比越小越经济而不是药费越便宜越好。     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.