Attenuation of postnatal hypoxia in the premature newborn rat by maternal treatment with dexamethasone: its relationship with lung phospholipid content

The effect of maternal treatment with dexamethasone on blood PO2, PCO2, pH and lactate concentrations and on lung phospholipid content in premature newborn rats during the early neonatal period was studied. The postnatal hypoxia shown by premature newborn rats was prevented by this treatment. Postnatal hypercapnia was longer in premature newborns showed significantly lower lung phospholipid concentrations than term-delivered newborn animals. Maternal treatment with dexamethasone increased lung phospholipid concentrations which reached values close to those found in term newborns. Our results suggest that maternal treatment with dexamethasone prevents postnatal hypoxia in the premature newborn rat by increasing the lung phospholipid content, which results in an enhancement of oxygen transfer through the alveolar membranes and the attenuation of hyperlactiacidemia.     

Effects of dexamethasone in hypoxic-ischemic brain injury in the neonatal rat

To clarify the effects of corticosteroids in neonatal hypoxic-ischemic brain injury, 7-day-old rats were subjected to unilateral common carotid artery ligation and hypoxia (Levine procedure) after being injected subcutaneously with saline, low-dose dexamethasone (4 mg/kg) or high-dose dexamethasone (40 mg/kg). Neither low-dose nor high-dose dexamethasone ameliorated the brain edema, lactacidemia, or hypoglycemia associated with hypoxia-ischemia. In addition, dexamethasone did not alter the pattern of neuropathologic damage or reduce the fall in brain high-energy phosphates. Finally, high-dose dexamethasone-treated animals experienced significantly more mortality than did either saline- or low-dose dexamethasone-treated animals. In this model of neonatal hypoxia-ischemia, dexamethasone did not confer any significant cerebral protection.     

内毒素血症对新生鼠脑一氧化氮合酶表达的影响

目的　在脑的正常发育及一些病理条件下 ,一氧化氮合酶 (NOS)发挥一定作用 ,但不同亚型的NOS作用不同。该研究观察正常新生鼠脑以及内毒素血症时新生鼠脑 3种一氧化氮合酶 (NOS)亚型蛋白的表达 ,并探讨脂多糖 (LPS)和地塞米松 (DXM)对其表达的影响。方法　生后健康 7日龄Wistar大鼠 6 8只 ,随机分为对照组、内毒素血症组 (腹腔内注射E .coliLPS 5mg kg)及DXM组 (LPS 5mg kg +DXM 10mg kg) ,分别于用药后2 ,4 ,6 ,2 4h取脑进行NOS免疫组织化学染色。结果　正常对照组新生大鼠脑神经元型NOS(nNOS)明显表达 ,内皮型NOS(eNOS)微弱表达 ,诱导型NOS(iNOS)无表达。LPS腹腔注射后 4hnNOS表达开始增加 ;eNOS及iNOS表达于 6h开始增加 ,3者表达均于 2 4h时达高峰 ;3种NOS表达阳性细胞主要分布于脑皮质、海马、下丘脑、脑室旁核团、纹状体神经细胞。除此之外 ,nNOS在梨状皮质有较强表达 ,eNOS及iNOS在血管内皮细胞呈微弱表达。3种NOS亚型蛋白表达在DXM注射后 2～ 6h受到明显抑制 ,并持续至用药后 2 4h。结论　正常新生鼠脑表达nNOS及eNOS ,无iNOS表达 ;LPS诱导 3种NOS亚型的表达 ,其表达的部位及受诱导表达的程度亦不同 ,提示NOS在中枢神经系统的正常发育及LPS诱导的内毒素血症脑损伤发病中发挥一定作用 ,DXM具有神     

Antenatal dexamethasone administration impairs normal postnatal lung growth in rats

Our purpose was to determine the influences of antenatal dexamethasone administration on neonatal lung development in rats. Dexamethasone (0.4 mg/kg maternal body weight per day) was administered i.p. on the 21st d (group 1) or on the 20th and 21st d (group 2) of gestation in Sprague Dawley rats with timed pregnancies. After natural deliveries, the lungs of the pups 1-60 d of age were removed and processed for morphometric analysis. In 60-d-old pups, groups 1 and 2 both showed a lower numerical density of alveoli and a larger mean alveolar radius than control pups. Antenatal administration of dexamethasone to rats impairs the normal postnatal lung growth. Some aspects of the use of antenatal glucocorticoid therapy in humans may require reconsideration.     

Neonatal hypoxia in the rat: effects on exocrine pancreatic development

BACKGROUND: Glucocorticoids profoundly affect pancreatic development during the suckling period. Increases in circulating glucocorticoids during exposure to hypoxia may alter the normal pattern of pancreatic enzyme development. METHODS: Rats were exposed to hypoxia from birth to 7 days (suckling) or from 28 to 35 days of age (weaned at day 21). RESULTS: Hypoxia in neonatal rats (0-7 days) led to decreased pancreatic weight, and trypsin, lipase, and amylase activity compared with normoxic controls. In contrast, rats exposed to hypoxia from 28 to 35 days of age had decreased lipase activity but no change in other pancreatic parameters. Two weeks after hypoxia (0-7 days) pups were returned to normoxia, and their body weights remained smaller than the age-matched, previously normoxic controls. Pancreatic enzyme activities were decreased in the group recovering from hypoxia compared with controls. Recovery of enzyme activities was observed 3 weeks after hypoxic rats were returned to normoxia. Normoxic pups were given dexamethasone to simulate the hyperglucocorticoid state in hypoxia at 7-day olds. Dexamethasone administration led to decreased body weight, but increased pancreatic weight and enzyme activity compared with normoxic, age-matched controls. CONCLUSIONS: Hypoxia in newborn rats delays the maturation of pancreatic exocrine enzymes. The mechanism is not related to increased serum glucocorticoids.     

Antenatal steroids and the developing brain

Randomised clinical trials show that two injections of corticosteroid into the mother before preterm delivery reduce respiratory distress syndrome, neonatal mortality, and intraventricular haemorrhage. However, repeated courses of antenatal steroid are not backed by such evidence of safety and efficacy. Animal studies have shown that maternal corticosteroid delays myelination and reduces the growth of all fetal brain areas particularly the hippocampus. Corticosteroids may reduce or enhance hypoxic-ischaemic injury to the developing brain depending on timing and dosage. Clinical trials of maternally administered corticosteroid show no evidence of increased disability on follow up but numbers are small. Postnatal trials of dexamethasone when brain maturity is still preterm show a significant increase in later disability in the dexamethasone treated groups. There is evidence from randomised trials, retrospective data, experiments on pregnant mice, and the chemical make up of the preparations that betamethasone may be safer and more protective of the immature brain than dexamethasone. Single course corticosteroid treatment before preterm delivery must still be recommended as a life saving and cost effective intervention, but clinicians may wish to change from using dexamethasone to betamethasone. In view of the animal and postnatal data, clinicians should be cautious with repeated courses of antenatal corticosteroids and repetition may be unnecessary for lung maturity.     

Chronic hypoxia and rat lung development: analysis by morphometry and directed microarray

It is unclear how sublethal hypoxia affects lung development. To investigate the effects of chronic hypoxia on postnatal lung remodeling, we treated neonatal rats with FIO2 of 0.12 for 10 d and analyzed lung development by morphometry and gene expression by DNA microarray. Our results showed the neonatal rats exposed to hypoxia reduced body weight by 42% and wet lung weight by 32% compared with the neonatal rats exposed to normoxia. In the neonatal rats exposed to hypoxia, the radial alveolar counts were decreased to 5.6 from 7.9 and the mean linear intercepts were increased to 56.5 mum from 38.2 mum. In DNA microarray analysis, approximately half of probed genes were unknown. Chronic hypoxia significantly regulated expression of genes that are involved in pathogenesis of pulmonary hypertension and postnatal lung remodeling. Chemokine ligand 12, jagged 2 were among those upregulated; c-kit, ephrin A1, and Hif-2alpha were among those downregulated. The altered expression of those genes was correlated with the lung development and remodeling.     

Pituitary-adrenal responses to acute hypoxemia during and after maternal dexamethasone treatment in sheep

The effects of maternal dexamethasone treatment on hypothalamic-pituitary-adrenal axis function were determined during basal and hypoxemic conditions in maternal and fetal sheep. Under halothane, ewes and their fetuses were catheterized at 117 d gestation (term = 145 d). Starting at 124 d, the ewes received i.m. injections of two doses of either dexamethasone (12 mg) or saline at 24-h intervals. All animals experienced one episode of hypoxemia when the dexamethasone was present in the maternal and fetal circulations [125 +/- 1 d (H1)] and a second episode of hypoxemia when the steroid was no longer detectable in either the maternal or fetal circulations [128 +/- 1 d (H2)]. The fall in partial pressure of oxygen in arterial blood in response to hypoxia was similar in the two episodes in both the fetal and the maternal blood. Maternal dexamethasone treatment diminished maternal and fetal basal plasma cortisol but not ACTH during the normoxic period of H1 but not H2. In control animals, hypoxemia induced increases in fetal but not maternal ACTH and cortisol concentrations. In dexamethasone-treated animals, maternal ACTH and cortisol concentrations also remained unchanged from baseline in both H1 and H2. In contrast, fetal plasma ACTH and cortisol responses to hypoxemia were significantly suppressed during H1 but not H2. Correlation of fetal plasma ACTH and cortisol concentrations suggested diminished cortisol output without a change in adrenocortical responsiveness in dexamethasone-treated fetuses during H1 but not H2. Maternal treatment with dexamethasone transiently suppressed maternal and fetal basal hypothalamic-pituitary-adrenal axis function and the fetal plasma ACTH and cortisol responses to acute hypoxemia in sheep.     

Early postnatal dexamethasone treatment and increased incidence of cerebral palsy

OBJECTIVE: To study the long term neurodevelopmental outcome of children who participated in a randomised, double blind, placebo controlled study of early postnatal dexamethasone treatment for prevention of chronic lung disease. METHODS: The original study compared a three day course of dexamethasone (n = 132) with a saline placebo (n = 116) administered from before 12 hours of age in preterm infants, who were ventilated for respiratory distress syndrome and had received surfactant treatment. Dexamethasone treatment was associated with an increased incidence of hypertension, hyperglycaemia, and gastrointestinal haemorrhage and no reduction in either the incidence or severity of chronic lung disease or mortality. A total of 195 infants survived to discharge and five died later. Follow up data were obtained on 159 of 190 survivors at a mean (SD) age of 53 (18) months. RESULTS: No differences were found between the groups in terms of perinatal or neonatal course, antenatal steroid administration, severity of initial disease, or major neonatal morbidity. Dexamethasone treated children had a significantly higher incidence of cerebral palsy than those receiving placebo (39/80 (49%) v. 12/79 (15%) respectively; odds ratio (OR) 4.62, 95% confidence interval (95% CI) 2.38 to 8.98). The most common form of cerebral palsy was spastic diplegia (incidence 22/80 (28%) v. 5/79 (6%) in dexamethasone and placebo treated infants respectively; OR 4.45, 95% CI 1.95 to 10.15). Developmental delay was significantly more common in the dexamethasone treated group (44/80 (55%)) than in the placebo treated group (23/79 (29%); OR 2. 87, 95% CI 1.53 to 5.38). Dexamethasone treated infants had more periventricular leucomalacia and less intraventricular haemorrhage in the neonatal period than those in the placebo group, although these differences were not statistically significant. Eleven children with cerebral palsy had normal ultrasound scans in the neonatal period; all 11 had received dexamethasone. Logistic regression analysis showed both periventricular leucomalacia and drug assignment to dexamethasone to be highly significant predictors of abnormal neurological outcome. CONCLUSIONS: A three day course of dexamethasone administered shortly after birth in preterm infants with respiratory distress syndrome is associated with a significantly increased incidence of cerebral palsy and developmental delay.     

The effects of maternal phlebotomy and orally-administered erythropoietin (Ep) on erythropoiesis in the suckling rat

Erythropoiesis was stimulated in 2- to 5-day-old neonatal rats suckled by phlebotomized mothers. This was established by increases in: hemoglobin levels, mean corpuscular hemoglobin concentration and percentages of peripheral reticulocytes. The oral administration of cow milk containing 4 IU human erythropoietin (Ep) to 10-day-old normal neonates for 4 days induced a reticulocytosis. Significant amounts of Ep appeared in the plasma of 1-day-old rats nursed by mothers bled 3 days prior to delivery as compared to nondetectable levels in 1-day-old control rats of normal mothers. The data suggest that Ep is transmitted to neonatal rats via maternal milk, and escapes inactivation, at least to some extent, in the process of absorption from the gastrointestinal tract with consequent stimulation of erythropoiesis in these animals.     

Increased plasma beta-hydroxybutyrate, preserved cerebral energy metabolism, and amelioration of brain damage during neonatal hypoxia ischemia with dexamethasone pretreatment

Dexamethasone (DEX) pretreatment has been shown to be neuroprotective in a neonatal rat model of hypoxia ischemia (HI). The exact mechanism of this neuroprotection is still unknown. This study used 31P nuclear magnetic resonance spectroscopy to monitor energy metabolism during a 3-h episode of HI in 7-d-old rat pups in one of two groups. The first group was pretreated with 0.1 mL saline (i.p.) and the second group was treated with 0.1 mL of 0.1mg/kg DEX (i.p.) 22 h before HI. Animals pretreated with DEX had elevated nucleoside triphosphate and phosphocreatine levels during HI when compared with controls. Saline-treated animals had significant decreases in nucleoside triphosphate and phosphocreatine and increases in inorganic phosphate over this same period. 31P nuclear magnetic resonance data unequivocally demonstrate preservation of energy metabolism during HI in neonatal rats pretreated with DEX. Animals pretreated with DEX had little or no brain damage following 3 h of HI when compared with matched controls, which experienced severe neuronal loss and cortical infarction. These same pretreated animals had an increase in blood beta-hydroxybutyrate levels before ischemia, suggesting an increase in ketone bodies, which is the neonate's primary energy source. Elevation of ketone bodies appears to be one of the mechanisms by which DEX pretreatment provides neuroprotection during HI in the neonatal rat.     

Dexamethasone effects on group B streptococcal infection in newborn rats

BACKGROUND: We previously published that human neutrophil-mediated bacterial killing of group B Streptococcus (GBS) in vitro was dependent on the timing and concentration of dexamethasone exposure. HYPOTHESIS: Dexamethasone treatment would affect neutrophil mediated killing of GBS in an animal model. METHODS: Wistar rat pups were randomly allocated to receive placebo or dexamethasone before, early or late after GBS infection. Suckling rats were infected with 104 or 105 colony-forming units of GBS or nothing. Pups were followed for survival, quantitative bacteremia, growth and neutrophil-mediated bacterial killing. Neutrophils for bacterial killing were obtained via cardiac puncture before infection. Statistics included chi square for survival, Mann-Whitney U test for bacteremia, analysis of variance for growth and paired Student's t test for bacterial killing analyses. RESULTS: Dexamethasone treatment before invasive GBS infection decreases quantitative bacteremia, improves survival and improves neonatal neutrophil-mediated bacterial killing in suckling rats, whereas dexamethasone treatment after infection increases bacteremia and decreases survival. Regardless of timing of dexamethasone treatment, before or after invasive GBS infection, growth was significantly impaired in all suckling rats receiving dexamethasone compared with controls. CONCLUSION: Treatment with dexamethasone before invasive GBS infection improves survival and decreases bacteremia in suckling rats; this appears in part to be mediated by improved neonatal neutrophil-mediated bacterial killing. We speculate that this improvement in outcome may be a result of improved number or function of neutrophil cell surface receptors.     

脑源性促红细胞生成素在新生鼠脑缺氧缺血后海马的表达变化

目的 探讨新生鼠脑缺氧缺血后海马CA1区腩源性促红细胞生成素(EPO)的表达,揭示脑缺氧缺血后内源性因素启动海马神经发生的可能机制.方法 7口龄SD新生大鼠结扎左侧颈总动脉并暴露在低氧环境造成新生大鼠缺氧缺血性脑损伤.选用192只大鼠,96只做免疫组织化学染色,96只做免疫印迹Westemblot分析.分别随机分为3组,即正常对照组、单纯缺氧组、缺氧缺血组,每组又分为1 h、6 h、16 h、1 d、3 d和7 d共6个时间点.应用免疫组织化学法和免疫印迹观察海马CA1区脑源性EPO的表达变化.结果 单纯缺氧、缺氧缺血EPO的表达与正常对照组比较,差异均有统计学意义;正常埘照组各时间点EPO的表达差异无统计学意义,单纯缺氧、缺氧缺血后16 h,脑源性EP0表达达到较高水平,与其余时间点比较差异有统计学意义,以后随时间延长逐渐下调.结论 脑源性EPO表达在新生鼠脑缺氧缺血后早期即增加,推测低氧、EPO早期高表达可能是参与海马神经发生的内源性因素之一.     

新生大鼠脑白质损害时神经细胞凋亡及bcl-2蛋白的表达变化

目的：研究表明脑白质损害与少突胶质前体细胞凋亡密切相关,bcl-2蛋白作为抗凋亡蛋白与新生大鼠脑白质损害(WMD)的关系较少报道。该文探讨bcl-2蛋白在新生大鼠脑白质损害(WMD)时的表达变化及意义。方法：将2日龄SD大鼠(n=90),随机分为两组,实验组(缺氧缺血)45只,对照组(假手术)45只,制成WMD模型;采用TUNEL法测定神经细胞凋亡及免疫组化（SP）法检测bcl-2蛋白在脑室周围白质区不同时间点的表达变化。结果：成功建立了WMD模型。实验组神经细胞凋亡在缺氧缺血后3 d达到高峰,凋亡指数脑白质为37.40±4.26,胼胝体为29.84±1.11,与对照组比较,在4 h,12 h,24 h,3 d,7 d 有统计学意义（P<0.05）。实验组bcl-2蛋白表达在WMD后1 h就上升,12 h达高峰,平均灰度值脑白质为124.96±0.27,胼胝体为130.09±0.77),在1 h,4 h,12 h,24 h,3 d的表达与对照组相比,差异有统计学意义（P<0.05）。结论： 新生大鼠脑白质损害时,bcl-2蛋白早期表达增高,而神经细胞凋亡高峰滞后,二者具有明显时序性,这种时序变化提示bcl-2蛋白可能对神经细胞具有一定保护作用。［中国当代儿科杂志,2007,9（2）：164-168］     

地塞米松对脓毒症新生大鼠nephrin的影响

目的观察脓毒症新生鼠肾小球足细胞裂孔隔膜蛋白nephrin、P-cadherin的表达及地塞米松对两者的影响,以探讨脓毒症蛋白尿的发生机制。方法新生10 d Wistar大鼠24只,采用脂多糖(LPS)腹腔内注射的方法诱导脓毒症模型,随机分为脓毒症组(SE组,n=12),地塞米松治疗组(DE组,n=12),DE组大鼠腹腔注射LPS 12 h后给予地塞米松0.3 mg/kg。另设出生10 d Wistar鼠为对照组(NC,n=10)。注射LPS 48 h后分别测定血清C-反应蛋白(CRP)、降钙素原(PCT)、中性粒细胞明胶酶相关载脂蛋白(NGAL),24 h尿蛋白(24 hUP)及尿足细胞(UPC)排泄水平;RT-PCR和Western-blotting检测肾小球nephrin、P-cadherin mRNA和蛋白质的表达。结果与NC组相比,SE组大鼠的CRP、PCT、NGAL、24 h UP水平均显著升高,差异有统计学意义(P均<0.01),UPC差异无统计学意义;nephrin、P-cadherin mRNA及蛋白质的表达明显下调。地塞米松明显改善LPS引起的CRP、PCT、NGAL、24 h UP升高,维持nephrin、P-cadherin mRNA及蛋白质的表达,对UPC的排泄无明显影响。结论地塞米松可减轻全身炎症反应,恢复肾小球nephrin、P-cadherin mRNA和蛋白质的表达,减轻蛋白尿。     

Effect of dexamethasone on pulmonary surfactant metabolism in hyperoxia-treated rat lungs

We have examined the effect of dexamethasone on the metabolism of pulmonary surfactant in normal and hyperoxia-treated rats. The relative abundance of the surfactant-specific apoprotein A (SP-A) mRNA in lung tissues and the contents of disaturated phosphatidylcholine (DSPC) and SP-A were measured in bronchoalveolar lavage fluids and in lung tissues in 4-wk-old rats exposed to room air or greater than 90% oxygen for 7 d with or without simultaneous treatment with dexamethasone (0.5 mg/kg body wt for 7 d). The relative abundance of the SP-A mRNA was marginally increased by hyperoxia (1.3-fold over controls). Dexamethasone increased the relative abundance of the SP-A mRNA to a level comparable to that with hyperoxia treatment (1.5-fold over controls). In lavage fluids, the contents of DSPC and SP-A were increased by 4- and 6-fold over controls by hyperoxia, respectively, but they were increased only by 2-fold by dexamethasone. In lung tissues, the contents of DSPC and SP-A were increased by 3- and 2-fold over controls by hyperoxia, respectively. These values in lung tissues in the air-exposed rats were not significantly increased by dexamethasone. In hyperoxia-treated rats, dexamethasone did not significantly affect the relative abundance of the SP-A mRNA level and the contents of DSPC and SP-A in lavage fluids and lung tissues. These results indicate that mechanisms other than increased synthesis of SP-A are involved in hyperoxia-induced SP-A accumulation and that dexamethasone does not affect the abnormal accumulation of pulmonary surfactant induced by hyperoxia.     

维生素 D 缺乏对子代大鼠肺形态结构及血小板源性生长因子-A 表达的影响

目的：研究孕期维生素 D（VitD）缺乏对子代大鼠肺形态发育及血小板源性生长因子-A（PDGF-A）表达的影响。方法：雌性Sprague-Dawley (SD) 大鼠随机分为对照组、VitD 缺乏模型组（每组6只）。对照组正常饲养;模型组予以避光、不含 VitD 的饲料喂养,2周后与成熟 SD 雄性大鼠交配,每组取孕20 d的胎肺及生后1 d 新生鼠肺,光镜及电镜下观察肺形态结构, RT-PCR 及 Western blot 分别检测肺组织PDGF-A mRNA及蛋白水平的表达。结果：光镜下,模型组子鼠肺泡平均表面积、平均呼吸膜周径均小于对照组（P<0.05）,平均肺泡间隔厚度大于对照组（P<0.05）;电镜下,模型组子鼠的板层小体数量明显少于对照组,成熟细胞器较少见。RT-PCR 及 Western blot结果显示模型组子鼠肺组织PDGF-A mRNA和蛋白表达水平均低于对照组（P<0.05）。结论：孕期 VitD 缺乏抑制孕晚期胎鼠及新生大鼠的肺形态发育。VitD 缺乏能显著抑制肺组织 PDGF-A 表达;PDGF-A表达减低可能是VitD缺乏抑制大鼠肺发育的重要机制之一。     

Brainstem involvement in neonatal herpes simplex virus type 2 encephalitis

Herpes simplex virus encephalitis in the newborn typically involves the cerebral cortex in a widespread manner. Herpes simplex virus type 2 rarely involves the brainstem. Here we report a 16-day-old infant with predominant brainstem and cerebellar involvement secondary to herpes simplex virus type 2 infection. Diffusion-weighted MRI performed 3 days after the onset of symptoms revealed restricted diffusion mainly in brainstem and cerebellar structures. No abnormal findings were seen on conventional MRI. Subsequent MRI scans showed evolution of the brain injury with extension along the corticospinal tracts. However, there was no evidence of any other supratentorial gray or white matter injury. This is the first report of predominant brainstem involvement in neonatal herpes simplex virus type 2 encephalitis. In addition, the importance of performing diffusion-weighted sequences to detect early central nervous system involvement and serial MRI to follow the evolution of central nervous system lesions is emphasized.     

缺氧缺血性脑损伤发病中神经干细胞变化规律初探

目的：探讨缺氧缺血性脑损伤后神经干细胞(NSCs)的变化规律。方法：取新生7日SD大鼠随机分为正常对照组、缺氧组和缺氧缺血组。每组再根据处死时间点随机分成3 h,6 h,1 d,3 d,7 d,14 d,21 d 7个亚组(n=10)。缺氧缺血组大鼠分离并结扎左颈总动脉,置于密闭缺氧箱2.5 h,缺氧组不结扎血管,仅缺氧2.5 h。免疫组织化学检测海马、皮层及纹状体区阳性NSCs数。结果：正常7日龄大鼠脑组织存在NSCs,且呈明显的区域性分布,在10日龄后数目逐渐减少。缺氧组及缺氧缺血组大鼠NSCs较正常组增多,差异有显著性,在缺氧后3d(10日龄)时达高峰,后逐渐减少,缺氧组在缺氧后21 d(28日龄)时仍高于正常组。结论：H IBD发病中早期NSCs增殖;NSCs随着病情的演变开始减少;早期采用NSCs干预治疗可能为临床治疗H IBD提供重要途径。     

大剂量地塞米松降低缺氧缺血性新生大鼠脑MCP-1蛋白表达

目的　研究新生大鼠缺氧缺血性脑病 (HIE)时脑组织单核细胞趋化蛋白 - 1(MCP - 1)的表达及地塞米松对其影响。方法　 2 5只新生大鼠分为 3组 :HIE模型对照组 (对照组 ) ,大剂量地塞米松治疗组 (大剂量组 ) ,小剂量地塞米松治疗组 (小剂量组 ) ;于造模后腹腔内分别注射生理盐水 10ml/kg ,地塞米松 10mg/kg及地塞米松 0 .5mg/kg ;2 4h后处死后取脑组织 ,免疫组化法检查脑组织MCP - 1蛋白的表达 ,光镜检查脑病理改变情况。结果　对照组、大剂量组、小剂量组的MCP - 1蛋白 ,神经细胞总数及变性 /坏死神经细胞数 ,分别为 7.98±1.37% ,0 .97± 0 .42 % ,7.2 5± 2 .45 % ;15 8.0 7± 14.48个 / 6HP ,2 0 3.2 5± 10 .2 7个 / 6HP ,15 5 .11± 16 .6 1个 / 6HP ,2 2 .86± 3.13个 / 6HP ,17.75± 3.45个 / 6HP ,2 3.89± 4.18个 / 6HP。与对照组相比 ,大剂量组MCP - 1蛋白表达减少 (P <0 .0 1) ,神经细胞总数增加 (P <0 .0 5 )及变性 /坏死神经细胞数减少 (P <0 .0 1) ,而小剂量组改变不明显(P >0 .0 5 )。结论　大剂量地塞米松可能通过降低HIE脑组织中MCP - 1蛋白表达对HIE脑组织损伤产生保护作用。