芦沙坦对轻、中度高血压病患者血小板活化和肾功能的影响

目的 :研究芦沙坦对轻、中度高血压病患者血小板活化和肾功能的影响 ,并探讨血小板活化和高血压性肾损害的关系。方法 :6 0例轻、中度高血压病患者随机分为两组 ,分别接受芦沙坦、氨氯地平治疗 3个月。治疗前后检测尿蛋白排泄率 (UAER)、血浆α颗粒膜蛋白 (GMP 14 0 )、血尿素氮 (BUN)、血肌酐 (Bcr)和肌酐清除率 (CCR)。结果 :①治疗后两组患者血压均明显下降 (P <0 .0 0 1) ,GMP 14 0和UAER均显著降低 (P <0 .0 0 1) ,BUN ,Bcr,CCR无明显变化 ;②两组患者治疗前、治疗后UAER与GMP 14 0呈显著正相关 (r分别为 0 6 9和 0 4 8) ,与血压下降无显著相关。结论 :①芦沙坦、氨氯地平能有效地控制轻、中度高血压病患者血压 ,减轻早期高血压性肾损害 ;②推测该药可能通过抑制血小板活化而对肾功能产生保护作用     

Tumor necrosis factor-alpha in whole blood cultures of preeclamptic patients and healthy pregnant and nonpregnant women.

OBJECTIVES: Tumor necrosis factor-alpha (TNF-alpha) is recognized as a likely mediator of the excessive endothelial activation and injury that is a key pathogenetic mechanism of preeclampsia. We used whole blood cell cultures from 12 patients with severe preeclampsia and from 12 healthy pregnant and nonpregnant women to determine the release of TNF-alpha by unstimulated leukocytes as a measure of their state of activation, and their response to stimulation with lipopolysaccharide (LPS) as an indicator of their state of priming. METHODS: Blood was cultivated without and with LPS, and TNF-alpha release was measured after six and 24 hours of cultivation by enzyme-linked immunoassays. Differential leukocyte counts were performed, and TNF-alpha values calculated per 10(5) monocytes. RESULTS: In unstimulated whole blood cultures, TNF-alpha release after six hours of cultivation was similar in all three groups; but after 24 hours, TNF-alpha concentrations in culture supernatants from preeclamptic patients were significantly higher than were values obtained in blood from normotensive pregnant women. In LPS-stimulated blood cultures with a maximum of TNF-alpha release at six hours cultivation time, TNF-alpha concentrations were significantly lower in preeclamptic women than they were in both control groups. We showed in an additional experiment that a strong LPS challenge following preactivation with high doses of LPS resulted in reduced release of TNF-alpha compared with release of TNF-alpha following preactivation with low doses of LPS. CONCLUSIONS: The observed high capacity for spontaneous TNF-alpha release by leukocytes in preeclampsia indicates activation of TNF-alpha producing leukocytes by the disease process. Preactivation and exhaustion of leukocytes by leakage of TNF-alpha could lead to the reduced response to TNF-alpha inducer LPS as observed in blood cultures from preeclamptic patients.     

共培养诱导小鼠ES细胞向软骨细胞分化的初步研究

目的 探讨软骨共培养体系诱导小鼠ES细胞向软骨细胞分化的可行性.方法 GFP标记的小鼠ES细胞初步分化为EB后,将EB消化为单个细胞,同猪关节软骨细胞按一定比例(1∶3)昆合后接种于PGA材料,体外培养1周后植入裸鼠皮下3周取材.对照组为EB细胞接种组及软骨细胞接种组.取材后行连续冰冻切片,切片分别做荧光拍照,HE染色及甲苯胺蓝染色.结果 组织学结果显示,EB细胞接种组形成畸胎瘤;软骨细胞对照组形成软骨组织;实验组形成软骨组织和畸胎瘤的混合体.甲苯胺蓝染色结果和荧光照片对照结果显示,部分软骨组织GFP阳性,由小鼠ES细胞分化而来.结论 软骨共培养体系可以诱导小鼠ES细胞向软骨细胞分化,但得到的软骨组织不纯,混有畸胎瘤组织.     

环缩酚肽抑制视网膜表达VEGF及PECAM基因和血管增生

[目的]观察两种环缩酚肽衍生物(Hep-A和Hep-B)对氧诱导的小鼠视网膜表达血管内皮生长因子(VEGF)和细胞黏附分子(PECAM;ICAM-1;VCAM-1)基因的影响及血管增生的变化.[方法]建立氧诱导的血管增殖性视网膜病变模型,12 d开始给小鼠皮下注安慰剂(第1组,n=7)、Hep-A 10 mg/kg(第2组,n=6)或者Hep-B 10 mg/kg(第3组,n=6),每天两次.5 d后取出左侧眼,分离视网膜并抽提RNA,用荧光定量PCR测出上述基因含量,并分别求出每个靶基因与标准基因S16含量的比率;右眼经心脏荧光素灌注后取眼球做视网膜平铺片,用图像分析软件定量计算视网膜新生血管的面积.[结果]视网膜中VEGF/S16的mRNA比率为:第1组(0.554±0.050),第2组(0.355±0.037),第3组(0.287±0.051);PECAM/S16为:第1组(2.050±0.249),第2组(1.228±0.153),第3组(1.027±0.210).经ANOVA分析,第2组和第3组分别与第1组比较,视网膜中VEGF基因表达分别减少36%和48.2%(P=0.001);PECAM基因表达分别减少40.1%(P＜0.05)和49.9%(P＜0.01);而VCAM-1和ICAM-1表达无明显差异.视网膜平片检测视网膜新生血管面积:第1组为(1.06±0.03)mm2/眼,第2组为(0.17±0.01)mm2/眼,第3组为(0.11±0.01)mm2/眼;经ANOVA分析,第2组和第3组分别与第1组比较,视网膜新生血管的面积明显减少(P＜0.001).[结论]两种环缩酚肽衍生物均抑制氧诱导的小鼠视网膜表达VEGF和PECAM基因,并抑制其形成视网膜新生血管.     

出血性蛇毒诱导血管内皮细胞凋亡的成分及作用机制研究进展

出血性蛇毒能专一性诱导血管内皮细胞(vascular endothelial cells，VEC)凋亡，研究人员已从中分离出5种VEC凋亡诱导成份，其中2种为L—aa氧化酶类，3种属于金属蛋白酶／解整联蛋白家族。研究证实前者可通过氧化VEC细胞膜上的L—leu产生H2O2而诱导其凋亡，后者则通过干扰膜整联蛋白与其配体的结合而使VEC凋亡。在由蛇毒诱导的VEC凋亡过程中，p53和bcl-2基因表达增加，且bcl-2的mRNA被剪辑成2条。已证实锚定依赖性信号分子αvβ3和磷脂信号分子PC-PLC参与该过程的信号转导。对该领域进一步研究，有望从蛇毒中纯化出或人工构建出专一地诱导肿瘤血管细胞凋亡的成分。本文总结了出血性蛇毒方面的研究进展。     

A novel cubic phase of medium chain lipid origin for the delivery of poorly water soluble drugs.

The existence of a novel cubic liquid crystalline phase is described within the pseudo-ternary system comprising lauric acid, monolaurin, and simulated endogenous intestinal fluid (SEIF). This phase behaviour has been characterized using cross-polarizing light microscopy (CPLM), and the structure of the cubic phase identified by small angle X-ray scattering (SAXS). The presence of the cubic phase was found to be temperature sensitive within the 20-37 degrees C range making it putative material for in situ gelation purposes. The cubic phase was shown to have a high capacity to solubilise a model poorly water-soluble drug, cinnarizine, and initial in vitro release data highlight the potential of this phase to provide sustained release. Absorption of cinnarizine from the cubic phase was studied in an unconscious rat model via duodenal administration and blood sampling via the carotid artery. The rate of absorption was significantly reduced when compared to a simple suspension formulation, a likely combination of retarded erosion of the cubic phase together with hindered drug release from the cubic matrix. The results of this study suggest that this cubic phase may potentially be of benefit in the delivery of poorly water-soluble compounds due to its high loading capacity and potential for sustained release. The ability to manipulate this system using temperature may warrant further interest in delivery applications via other routes of administration.     

实验性肌炎动物模型制作的研究

目的建立实验性肌炎动物模型，研究特发性炎性肌病的发病机制。方法将50只健康的雄性SD大鼠随机分成两组：模型组40只，对照组10只。兔骨骼肌制备肌匀浆。模型组用肌匀浆与弗氏完全佐剂完全乳化后皮下免疫注射1ml．对照组用生理盐水替代肌匀浆，每周免疫1次，连续免疫5次。前2周同时腹腔注射百日咳毒素1ml。分别于免疫注射后各周取大鼠的骨骼肌组织，观察其肌活检病理、免疫组织化学的改变，同时检测血清肌酶水平，并与人类炎性肌病比较。结果模型组肌酶升高与对照组间有显著差别。病理改变以骨骼肌多发性炎症为特点：横纹肌呈灶性分布的肌纤维变性、坏死，横纹消失；周围炎性细胞浸润；肌纤维粗细不等、染色不一。病理分级以2a级为主。单个核细胞浸润以CD8^＋T细胞为主．主要定位于肌内膜。骨骼肌细胞膜上主要组织相容性复合体（MHC）-Ⅰ类分子表达增加。结论用异种动物骨骼肌匀浆免疫大鼠可诱导出炎性肌病动物模型，与人类炎性肌病在临床表现、组织病理和免疫组织化学方面有相似之处。