大肠癌患者VEGF和NO血清水平及其与恶变程度的关系

目的:研究血清中血管内皮生长因子(VEGF)和一氧化氮(NO)表达水平及其与大肠癌恶变程度的关系。方法:分别采用酶联免疫吸附法(ELISA)测定和分光光度法检测46例大肠癌患者术前和30例健康人血清中VEGF和NO的含量。结果:大肠癌患者血清VEGF和NO表达水平均较健康人明显增高(P<0.01),且随着大肠癌浸润深度增加、有淋巴结转移以及Dukes分期愈晚者而显著增高(P<0.01)。血清VEGF与NO含量呈明显正相关(r=0.8152,P<0.01)。结论:VEGF和NO与大肠癌的发生、发展及转移调控过程有关,术前检测血清VEGF和NO含量对判断大肠癌的浸润转移以及Dukes分期具有重要价值。     

胃泌素对大鼠胃粘膜环氧合酶及生长因子表达的影响

目的：探讨胃泌素对大鼠胃粘膜环氧合酶（COX）及生长因子表达的影响。方法：雄性SD大鼠皮下注射胃泌素1 μg/kg、10 μg/kg或100 μg/kg，Western blot和免疫组化检查胃粘膜COX-1、COX-2、肝细胞生长因子（HGF）和肝素结合表皮生长因子样生长因子（HB-EGF）表达。评价胃泌素受体拮抗剂YM022对COX-1、COX-2、HGF和HB-EGF表达的影响。结果：胃泌素剂量依赖性地增加大鼠胃粘膜COX-2和HB-EGF表达，而对COX-1和HGF表达无明显影响；YM022阻断胃泌素诱导的COX-2和HB-EGF表达。 结论： 胃泌素调节大鼠胃粘膜COX-2和HB-EGF蛋白表达，提示COX-2和HB-EGF参与与胃泌素相关联的胃粘膜增生和胃癌等的发病过程。     

糖尿病大鼠骨质疏松与过氧亚硝基阴离子关系的免疫组化研究

目的：探讨过氧亚硝基阴离子（ONOO-）与糖尿病（DM）骨质疏松（OP）的关系。 方法： 用链脲佐菌素(STZ)诱导糖尿病大鼠模型12周后，进行骨密度（BMD）检查、观察股骨胫骨形态学改变, 应用免疫组化法检测骨中和高糖溶液培养成骨细胞（OB）中的诱导型一氧化氮合酶(iNOS)、ONOO-水平的变化。 结果： 高糖溶液培养OB中的iNOS和ONOO-升高；DM大鼠骨中的iNOS和ONOO-升高、BMD降低、骨形态学呈退行性改变。 结论： 骨中iNOS、ONOO-增加可能是糖尿病OP的发病机制之一。     

口虾蛄(Oratosquilla oratoria)神经系统一氧化氮合酶的NADPH-d组织化学定位研究

运用NADPH-d组织化学整体染色的方法研究了甲壳纲动物—口虾蛄神经系统一氧化氮合酶(NOS)的分布。脑神经节中有少量来自腹神经链的纤维呈阳性;每侧联合神经节中各有一个阳性细胞(直径约75μm);食道下神经节的阳性细胞可分为两类,即小型强阳性细胞(直径约40μm)和大型弱阳性细胞(直径约90μm),前者的阳性突起构成节间联系;胸神经节的阳性细胞也可分为两种类型,每节有4个小型强阳性反应细胞(直径约60μm)和6~10个大型弱反应细胞(直径约80μm),小细胞发出的突起进入中央纤维网尔后构成不同体节的神经节间联系;腹部前五个体节的神经节中各有5对阳性细胞(直径约80μm),腹部最后一个神经节阳性细胞数量较多,其末端有一对阳性细胞(直径约55μm)其突起经中线处交叉后前行进入腹神经索。结果说明:NOS广泛存在于口虾蛄神经系统中,NO作为信息分子参与其信息传递过程。     

Fetal programming of adult hypertension in female rat offspring exposed to androgens in utero

Aims

The influence of prenatal factors on the development of arterial hypertension has gained considerable interest in recent years. We examined the effects of prenatal testosterone treatment on blood pressure in adult female rats. Further, to define the mechanisms whereby blood pressure may be raised, we examined vascular endothelial function and nitric oxide synthesis.

Methods and Results

Testosterone propionate (0.5 mg/kg/day; SC) or vehicle was administered to pregnant Sprague-Dawley rats from gestational day 15-19. Maternal feed intake and plasma levels of steroid hormones were measured in the dams. In the female offspring, birth weight, growth rate, blood pressure, vascular reactivity, eNOS expression, and nitric oxide production were examined. In the pregnant rats, testosterone-treatment increased plasma testosterone levels by 2-fold without any significant changes in 17β-estradiol, progesterone and corticosterone levels. Testosterone-treatment did not affect maternal feed intake. The pups born to testosterone mothers were smaller in size but exhibited catch-up growth. The blood pressure in the testosterone offspring at 6 months of age was significantly higher compared to controls. Endothelium-intact mesenteric arteries from testosterone group exhibited increased contractile responses to phenylephrine, decreased vasodilation to acetylcholine and unaltered responses to sodium nitroprusside in comparison to control rats. Testosterone rats demonstrated decreased expression for eNOS, and reduced nitric oxide production.

Conclusions

Our data show that elevated plasma maternal testosterone levels: (1) causes low birth weight followed by catch-up growth and hypertension in female offspring and (2) alters endothelium-dependent vascular responses. The endothelial dysfunction is associated with decreased activity/expression of eNOS.     

Maternal obesity induced by a ‘cafeteria’ diet in the rat does not increase inflammation in maternal,placental or fetal tissues in late gestation

IntroductionObesity during pregnancy can cause serious complications for maternal and infant health. While this has often been attributed to increased inflammation during obese pregnancy, human and animal studies exhibit variable results with respect to the inflammatory status of the mother, placenta and fetus. Cafeteria (CAF) feeding induces more inflammation than standard high-fat feeding in non-pregnant animal models. This study investigated whether maternal obesity induced by a CAF diet increases maternal, fetal or placental inflammation.MethodsMaternal obesity was established in rats by 8 weeks of pre-pregnancy CAF feeding. Maternal plasma inflammatory markers (IL-1β, IL-6, IL-10, IL-12p40, MCP1, GRO/KC, MIP-2 and TNFα) and expression of inflammatory genes (Tnfα, Il-6, Il-1β, Tlr2, Tlr4, Cox2 and Emr1) in maternal, placental and fetal tissues were measured at day 21 of gestation.ResultsDespite CAF animals having 63% more central body fat than controls at day 21 of gestation, plasma inflammatory markers were not increased; indeed, levels of IL-6, IL-12p40 and MIP2 were reduced slightly. Similarly, inflammatory gene expression remained largely unaffected by CAF feeding, except for slight reductions to Tlr4 and Emr1 expression in CAF maternal adipose tissue, and reduced Tlr4 expression in male labyrinth zone (LZ). The junctional zone (JZ) displayed increased Il-6 expression in CAF animals when fetal sexes were combined, but no inflammatory genes were affected by the CAF diet in fetal liver.ConclusionsMaternal obesity induced by a CAF diet before and during pregnancy does not increase the inflammatory status of the mother, placenta or fetus in late gestation.     

Prophylactic treatment for preeclampsia in high-risk teenage primigravidae with nitric oxide donors: a pilot study

Objectives: Preeclampsia is associated with significant morbidity and mortality especially in high-risk groups. Impairment of endogenous nitric oxide has been shown to be associated with the disease and prophylactic therapy may ameliorate this condition and improve pregnancy outcome. This study valuated nitric oxide donors prophylactic treatment for preeclampsia in high-risk teenage primigravidae.

Methods: The study included three hundred primigravidae aged?≤?20 years with singleton pregnancy. Abdominal pulsed color Doppler ultrasound was done at 24 weeks gestation and pregnancies with uterine artery diastolic notch were randomly allocated to a control group received placebo vaginal tablets and a study group received isosorbid mononitrate 20?mg tablet once daily applied vaginally until delivery.

Outcomes: Incidence of preeclampsia and maternal, fetal, and neonatal outcome in both groups.

Results: The study group had significant lower incidence of preeclampsia, preterm birth, intrauterine growth restriction and of neonatal admission to the intensive care (p?<?0.05).

Conclusions: Nitric oxide donors prophylactic treatment for preeclampsia in high-risk teenage pregnancies decrease the incidence of preeclampsia and improve maternal, fetal, and neonatal outcomes. Further studies on larger sample size are required to confirm these results.     

高氧暴露对早产大鼠肺组织中HO-1与iNOS表达的影响

目的：探讨血红素加氧酶-1（HO-1）与诱导型一氧化氮合酶（iNOS）在高氧肺损伤大鼠中的表达及作用。方法：将3日龄早产Sprague-Dawley大鼠64只随机分为高氧组、空气组（每组32只）,于实验 3 d及 7 d时,分别检测空气组和高氧组肺组织 HO-1活性、肺泡灌洗液中 NO、肺组织病理学改变及 HO-1、iNOS 在肺内的分布和表达(免疫组织化学方法)。结果：3 d、7 d高氧组存在明显急性肺炎症性改变,iNOS 在中性粒细胞的表达、灌洗液中 NO 含量明显高于空气组 (P均<0.01),且7 d高氧组高于3 d高氧组(P<0.05);3 d、7 d 时高氧组巨噬细胞 HO-1 表达高于空气组(分别P<0.05,P<0.01),且7 d高氧组显著高于3 d高氧组(P<0.01) 。结论：HO-1 与 iNOS在高氧肺损伤大鼠中的表达是增高的,HO-1 与 iNOS 均可能参与了高氧肺损伤。     

高频振荡通气联用一氧化氮吸入在新生儿气胸中的应用

目的 探讨高频振荡通气(HFOV)联用一氧化氮(NO)吸入治疗新生儿气胸的疗效.方法 选择2003年7月-2008年10月本院新生儿科收治的37例气胸新生儿,均行床边X线胸片,提示肺组织压缩均超过60%,在出现气胸后均接受胸腔闭式引流及机械通气.37例气胸新生儿依治疗方法不同分为2组:HFOV组和HFOV+NO组.HFOV组17例,在出现气胸后机械通气模式选择HFOV治疗;HFOV+NO组20例,在给予HFOV治疗的同时吸入NO,吸入NO水平为(5～15)×10-6.2组在治疗2 h、12 h、24 h 及以后每24 h行血气分析,并详细记录呼吸机参数,计算氧合指数(OI),持续监测NO/NO2水平.结果 2组治疗后2 h氧合情况持续改善,OI值、吸入氧浓度(FiO2)、平均呼吸道压均逐渐降低,动脉血氧分压均升高,但HFOV+NO组较HFOV组改善更显著(Pa＜0.05).HFOV+NO组上机时间(88.2±19.8) h,使用FiO2≥0.8时间(5.4±3.5) h;HFOV组上机时间(105.8±22.5) h,使用FiO2≥0.8时间(15.7±8.2) h.2组在上机时间、使用高浓度氧时间方面比较,差异均有统计学意义(Pa＜0.05).结论 HFOV 联用NO吸入治疗新生儿气胸可迅速改善氧合,纠正低氧血症,缩短高浓度氧及呼吸机使用时间,提高抢救成功率.     

吸入一氧化氮对胎粪吸入综合征新生猪脑的保护作用

目的探讨机械通气下吸入一氧化氮（NO）对胎粪吸入综合征（MAS）新生猪脑不同部位胆碱能神经元的保护作用及对星形胶质细胞增殖的影响。方法 建立新生猪胎粪吸入模型,并予间歇正压通气,随机分为胎粪吸入组（n=10）和NO治疗组（n=4）,另设正常对照组（n=4）。HE染色计数大脑皮质、海马及基底节神经元细胞,免疫组化法检测皮层、海马及基底节胆碱乙酰基转移酶（ChAT）和胶质纤维酸性蛋白（GFAP）免疫阳性细胞数。结果 胎粪吸入组脑不同部位的神经元细胞和ChAT阳性细胞数均较正常对照组减少[神经元细胞：皮质（29.6±2.3）比（58.2±3.8）,海马（27.0±12.7）比（56.0±3.7）,基底节（25.0±4.6）比（56.0±4.6）;ChAT阳性细胞：皮质（16.7±3.9）比（38.3±9.0）,海马（17.5±2.7）比（34.3±11.6）,基底节（17.0±1.2）比（35.3±7.1）,P均〈0.01],GFAP阳性细胞数增多[皮质（54.8±11.0）比（22.0±5.5）,海马（54.9±14.7）比（21.0±1.7）,基底节（53.8±7.1）比（19.0±4.6）,P均〈0.001）]。NO治疗组神经元细胞数和ChAT阳性细胞数均多于胎粪吸入组,GFAP阳性细胞数少于胎粪吸入组,P均〈0.05。结论 新生猪MAS后吸入NO可减少脑不同部位胆碱能神经元的丢失及星形胶质细胞的增殖,提示吸入NO可能对MAS引起的脑损伤具有保护作用。