造血细胞表达血管内皮生长因子及其受体基因的研究

目的 探控血管内皮生长因子（VEGF）及其受体Flt-1和KDR基因在造血细胞中的表达。方法 提取正常外周血、骨髓单个核细胞及血液肿瘤细胞系的总RNA,以β2-微球蛋白基因为内标,用单定量逆转录聚合酶链反应（RT-PCR）分析VEGF,Flt-1和KDR基因的表达。结果 在22份正常外周血和22份非恶性骨髓标本中,分别有18份和19份表达,VEGF基因,而10种人类血液肿瘤细胞系均有VEGF基因的高度表达。在12份外周血中,有4份检测到Flt-1基因表达,但均未见有KDR基因表达;在22份骨髓中,分别有9份和14份表达Flt-1基因或KDR基因。10种血液肿瘤细胞系有6种表达Flt-1基因,而KDR基因表达仅见于Raji细胞。血小板也有VEGF和Flt-1基因的低度表达。结论 VEGF作为血管生成的介导物,可能具有调节正常造血细胞和血液肿瘤细胞生长的作用。     

重组人生长激素对败血症大鼠氧化损伤和抗氧化损伤的影响

目的观察重组人生长激素(rhGH)对败血症大鼠氧化损伤和抗氧化损伤的影响。方法采用ipE.coli复制大鼠败血症模型。42只♀SD大鼠随机分为正常对照组(C组)、败血症组(S组)及rhGH治疗组(T组),S组、T组依观察时点再分为S1d、S3d和T1d、T3d两个亚组。观测3组的血浆硫代巴比妥酸反应物(TBARS)水平及超氧化物歧化酶(SOD)活力。结果S组大鼠血浆TBARS水平在各时点均明显高于C组和T组;T组各时点与C组无明显差异;S组大鼠血浆SOD活力在各时点均明显低于C组;T1d组与C组相比虽无显著差异,但却明显高于S1d组,T3d组明显高于C组及S3d组。结论rhGH能明显提高机体的抗氧化损伤能力。     

K252a对腺样囊性癌培养中许旺细胞生长的阻断作用

目的观察并探讨K252a在体外坐骨神经长出的许旺细胞对腺样囊性癌细胞趋化生长中的影响。方法采用细胞培养技术,将经神经营养素的高亲和受体Trk特异性阻断剂K252a预处理的小鼠坐骨神经与腺样囊性癌细胞共培养（设24组）,以正常小鼠坐骨神经与腺样囊性癌细胞共培养为对照组（设24组）;结果与对照组相比,经K252a预处理的坐骨神经与腺样囊性癌细胞共培养长出的许旺细胞增生组数及趋化性生长组数X^2值分别为14．03、26．32,P值均小于0．025,说明两组之间的差异非常显著,许旺细胞丧失趋化性及细胞增生未被促进。结论K252a在许旺细胞对腺样囊性癌细胞趋化生长中的阻断作用间接地表明神经营养素可促进许旺细胞增生及向腺样囊性癌细胞趋化迁移,这可能是腺样囊性癌嗜神经性重要机制之一。     

不同宫内发育状况新生儿血清GH、IGF-1、IGFBP-3水平与出生体重、胎龄相关性的研究

目的 研究不同宫内发育状况新生儿在不同胎儿发育阶段血清生长因子(GH)、胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)的水平变化,探讨适于胎龄儿和小于胎龄儿CH、IGF-1、IGFBP-3分泌与胎儿体重和胎龄的相关规律.方法 用放射免疫法(mA)测定不同胎龄出生的80例适于胎龄儿(AGA)和72例小于胎龄儿(SGA)的血清GH、IGF-1、IGFBP-3水平,并比较两组GH、ICF-1、IGFBP-3水平,分别对两组婴儿的GH、IGF-1、ICFBP-3水平与其出生体重、胎龄作直线相关分析和偏相关分析或曲线拟合.结果 AGA组CH、IGF-1、IGFBP-3水平高于SCA组(P＜0.01),同组男女婴之间GH、IGF-1、IGFBP-3水平差异无统计学意义(P＞0.05).AGA组婴儿的GH、IGF-1与出生体重呈正相关(P＜0.05),而CH、IGF-1、IGFBP-3与胎龄无直线相关关系(P＞0.05),但呈三次函数(Cubic)的曲线分布规律(R2分别为0.64、0.63、0.54,P＜0.01);SGA组婴儿的CH、IGF-1、IGFBP-3与出生体重无直线相关性(r分别为-0.18,0.01,-0.15,P分别为0.25,0.93,0.19),也不呈曲线分布(P＞0.05),GH与胎龄负相关(r=-0.41,P=0.01),IGF-1、IGFBP-3与胎龄均无直线相关性,也不呈曲线分布(P＞0.05).结论 AGA组婴儿的CH、IGF-1表现为胎龄和体重依赖性分泌,GH、IGF-1随出生体重的增长分泌增多,妊娠34周后GH、IGF-1、IGFBP-3的分泌量明显增多;SGA组婴儿GH随胎龄的增长分泌量下降,IGF-1、ICFBP-3无胎龄和体重依赖性特点,妊娠34周后GH、ICF-1、IGFBP-3无分泌高峰出现可能与宫内发育迟缓有关.     

中药生物药剂学分类系统的多成分溶出评价方法在葛根芩连片中的应用

该研究是中药生物药剂学分类系统(biopharmaceutics classification system of Chinese materia medica,CMMBCS)用于中成药评价的实例,重点评估可能影响多成分吸收时序的溶出同步性问题。实验采用HPLC测定复方葛根芩连片中9种成分在不同溶出介质中不同时间点的累积溶出百分率,绘制体外溶出曲线,采用相似因子(f₂)和聚类分析进行溶出曲线的相似性比较分析,结果表明在水介质中,峰7和峰8(黄芩苷)所代表的成分与2号参比峰(葛根素)相似性较差,相似因子均为43;在pH 7.4介质中,峰7和峰8(黄芩苷)所代表的成分与2号参比峰(葛根素)相似性较差,相似因子分别为31和45;其他介质中各峰所代表的成分与2号参比峰(葛根素)均相似性较好。该实验表明峰3,4,5和6(小檗碱)所代表的成分与2号参比峰(葛根素)具有完全同步溶出的特性;峰1和峰9所代表的成分与2号参比峰(葛根素)具有基本完全同步溶出的特性;峰7和峰8(黄芩苷)所代表的成分与2号参比峰(葛根素)不具有同步溶出的特性。     

白花蛇舌草水提物抗白血病CEM细胞的增殖作用及机制

目的 观察白花蛇舌草水提物对CEM细胞增殖影响及其机制.方法 对CEM细胞进行细胞培养.采用台盼蓝拒染法,镜下计数活细胞数,绘制生长曲线,检测白花蛇舌草水提物对CEM细胞的生长抑制作用;琼脂糖凝胶电泳法检测白花蛇舌草水提物对CEM细胞的诱导凋亡作用.结果 白花蛇舌草水提物终浓度0.64,3.2,16μg/ml均显著抑制CEM细胞的生长,且呈剂量和时间依赖性.琼脂糖凝胶电泳结果显示实验组出现明显的DNA梯形凋亡条带,而空白对照组没有出现梯形条带.结论 白花蛇舌草水提物对CEM细胞生长具有显著抑制作用,诱导肿瘤细胞凋亡可能是其主要机制之一.     

The PRB-dependent FOXO1/IGFBP-1 axis is essential for progestin to inhibit endometrial epithelial growth

Progestin inhibits the growth of normal and cancerous endometria via the progesterone receptor (PR), but the distinct functions and signalings of PR subtypes have not been fully understood. The aim of the present study was to dissect the key pathways of progestin to inhibit endometrial epithelial growth. Immortalized endometrial epithelial cells (EM-E6/E7/TERT) with stable PRA or PRB expression were established and used for the experiments. In vitro growth inhibition by progestin was mainly observed in EM-E6/E7/TERT cells with PRB rather than those with PRA. RT-PCR assay confirmed that FOXO1, a key gene for progestin action, was up-regulated by progestin in a PRB-dependent manner. cDNA microarray analysis identified IGFBP-1, which contains FOXO1 binding sites on its promoter, to be induced by medroxyprogesterone acetate (MPA) in EM-E6/E7/TERT cells with PRB but not with PRA. siRNA knockdown of FOXO1 disturbed the induction of IGFBP-1 by MPA, while IGFBP-1 knockdown showed no effect on MPA-induced FOXO1 expression, indicating that FOXO1 is an upstream regulator of IGFBP-1. Luciferase reporter assays showed that MPA activated the IGFBP-1 promoter, which was cancelled by FOXO1 knockdown. Chromatin immunoprecipitation assay confirmed the in vivo binding of FOXO1 to the core promoter of IGFBP-1. IGFBP-1 knockdown significantly attenuated the growth inhibitory effects of MPA. The FOXO1/IGFBP-1 axis is essential for PRB-dependent growth inhibition of endometrial epithelial cells, offering a potential therapeutic clue to enhance the progestin effect.     

Left ventricular isovolumic relaxation and renin-angiotensin system in the growth restricted fetus

OBJECTIVE: To determine left ventricular isovolumic relaxation time (LV IRT) in normally developing and growth restricted fetuses (FGR) as an indicator of fetal cardiac afterload and neonatal systolic blood pressure. STUDY DESIGN: A prospective longitudinal study in 124 normally developing and 47 growth restricted fetuses (FGR). LV IRT, fetal heart rate (FHR) and umbilical artery pulsatility index (PI) were determined at 2-3 week intervals starting at 22-26 weeks of gestation until delivery. Renin and angiotensin I levels were measured by radioimmunoassay in umbilical venous blood after delivery. Systolic blood pressure was measured at day 1 and day 5 of postnatal life. To evaluate the association between LV IRT, gestational age and FHR, bivariate regression analyses were performed. RESULTS: Mean LV IRT (62+/-8ms) was 29 percent longer in FGR as compared to the normal subset (47+/-6ms) at all gestational ages (p<0.001). Mean postnatal active plasma renin level (7.78+/-S.D. 1.03ng/ml) and postnatal angiotensin I level (4.21+/-0.70ng/ml) in the FGR subset were significantly higher (p<0.001) than in the normal subset (4.81+/-1.04ng/ml, renin and 2.69+/-0.44ng/ml, angiotensin I). There was a significant difference (p<0.01) in systolic blood pressure between the two subsets on postnatal day 1 (FGR 52+/-6mmHg vs. normal 46+/-4mmHg) and day 5 (FGR 76+/-5mmHg vs. normal 60+/-6mmHg). CONCLUSION: Left ventricular isovolumic relaxation time may act as a sensitive index of increased arterial afterload in the growth retarded fetus and may herald raised systolic blood pressure in the early neonatal period.     

Customized birthweight standards for a Spanish population

OBJECTIVE: To analyse the biological factors affecting birthweight and to derive customized birthweight standards for a Spanish population. METHODS: A retrospective cohort was created with all the singleton pregnancies delivered at term and free of pathology in our Institution. Birthweight was modeled by multiple linear regression from maternal (ethnic origin, maternal height, booking weight, smoking, and parity), and fetal (gender, gestational age) characteristics. RESULTS: In addition to gestational age and sex, height, booking weight, ethnic origin, parity, and smoking all have significant and independent effects on birthweight. Women from East-Asia, Morocco and South-America had newborns on average 83 g, 74 g and 95 g heavier than White-European Spanish women. The effect of smoking was found to be dose-related. CONCLUSION: We found the relative effect of the maternal and fetal characteristics to be very similar to that reported in previous studies. We report coefficients for ethnic groups that account for a sizeable proportion of the population composition of several European countries.