Re-Expression of Pulmonary Surfactant Proteins Following Tracheal Obstruction in Fetal Sheep

Increased fetal lung expansion, induced by tracheal obstruction (TO), is a potent stimulus for fetal lung growth, but rapidly reduces surfactant protein (SP) mRNA levels. Our aim was to determine the time course for the re-expression of the surfactant proteins in fetal lung tissue following the release of a TO and to relate these to the changes in lung liquid volume. Fetal sheep were exposed to either: (1) no treatment (controls); (2) 4 days of TO; (3) 4 days of TO, followed by release of the obstruction for 24 h; (4) 4 days of TO followed by release of the obstruction for 3 days. Four days of TO increased lung liquid volumes from 26.8 +/- 1.9 to 72.0 +/- 5.6 ml kg(-1) and reduced SP-A, SP-B and SP-C mRNA levels to 38.5 +/- 10.7, 56.8 +/- 10.3 and 18.3 +/- 5.3 % of control values, respectively. One day after TO release, lung liquid volumes were reduced to 17.4 +/- 5.3 ml kg(-1) (control 128 days, 31.0 +/- 3.8 ml kg(-1)) and SP-A and SP-B mRNA levels were not different from control levels. In contrast, SP-C mRNA levels only increased to 45.4 +/- 17.3 % of control. Three days after TO release, lung liquid volumes increased to 48.0 +/- 8.5 ml kg(-1) and SP-A and SP-B mRNA levels were reduced to 48.8 +/- 10.2 % and 71.5 +/- 19.8 % of control, respectively; SP-C mRNA levels remained at 35.3 +/- 12.3 % of control. Following the release of a TO, SP-A, SP-B and SP-C mRNA levels were closely and inversely related to the volume of lung liquid. Based on these relationships, the lung liquid volumes that equate to 100 % expression were considerably less than control lung volumes (< 10 vs. 30-40 ml kg(-1)) in fetuses of this age. Thus, the changes in fetal lung SP-A, SP-B and SP-C mRNA levels following the release of a TO are variable, differ between the proteins and are closely related to the changes in lung liquid volumes. We conclude that the re-expression of surfactant proteins following TO is variable and that the change in lung liquid volume is potentially a good indicator for surfactant protein re-expression. Experimental Physiology (2001) 86.1, 55-63.     

Heterotopic pancreas of the stomach. Histogenesis and immunohistochemistry.

Ordinary histological investigation has suggested that heterotopic pancreas of the stomach may have two types of histogenesis; one is development from immigrated fetal pancreas tissue, and the other is development from primitive gastric mucosal epithelium following penetration into the submucosa with subsequent erroneous differentiation into pancreas tissue. It is suspected that type-I lesions include the majority of cases caused by immigration from fetal pancreas, and that some type-II cases arise through erroneous differentiation of primitive gastric mucosal epithelium. With regard to immunohistochemical findings, cells positive for pancreatic polypeptide and amylase were much more numerous in the acini of type-I cases compared with type-II cases. Positive cells were found not infrequently in the acini of type-II cases after staining for pancreatic polypeptide, insulin, glucagon, somatostatin, serotonin, and gastrin. On the other hand, a small number of cells in islets were not infrequently positive for alpha 1-antitrypsin, alpha 1-antichymotrypsin, and amylase. It is considered that in the heterotopic pancreas, ductal cells have the potential to differentiate into acinar cells and islet cells, as is the cases in the orthotopic pancreas.     

Evolution of endotoxin-induced lung injury in the rat beyond the acute phase.

OBJECTIVES: Intratracheal endotoxin in rats causes acute lung injury. Here we have addressed the cellular physiopathology of lung recovery from that injury. METHODS: The lungs of 5 untreated rats and rats treated with intratracheal endotoxin from 2, 3, 5, 8 (5 rats each) and 15 days (2 rats) were studied by light and electron microscopy and immunohistochemistry. RESULTS: In the acute phase there was a reduction in the aerated spaces (p < 0.01); diffuse infiltration of granulocytes and macrophages; hyperplasia of type-II pneumocytes, and hypertrophy of interstitial cells. Aerated spaces improved during recovery. In the early recovery phase (3-8 days) the compartmentalization of infiltrating cells varied significantly (p < 0.01): macrophages remained widespread while neutrophils were inside blood vessels. Many pneumocytes were intermediate between type-I and type-II cells. In the late recovery phase (15 days) the infiltrate disappeared; myofibroblasts were significantly more than previously (p < 0.01) and extracellular matrix was abundant; type-II pneumocytes contained non-lamellated lipid inclusions. CONCLUSIONS: Macrophages play a pivotal role in the damage-repair processes of the lung following endotoxin injury, leading to an increase in extracellular matrix, differentiation of myofibroblasts and altered secretion of surfactant by newly differentiated type-II pneumocytes.     

双下肢不等长与原发性膝骨关节炎的关系及影像学特点的相关性研究

目的 探讨双下肢不等长(LLD)与原发性膝关节骨关节炎(KOA)发病的关系及影像学特点,为KOA的防治提供一定的理论依据。方法 回顾性分析2017年6月-2019年8月北京博爱医院行人工膝关节置换术(TKA)的141例原发性KOA患者的临床及影像资料。其中男19例,女122例;年龄(67.8±9.4)岁;体质量指数(BMI) 为(26.8±2.9)kg/m²。患者术前行双下肢全长CT检查,应用WebViewer软件测量双下肢骨骼长度、双侧解剖股骨胫骨角(AFTA)和骨盆倾斜角(PTA)。拍摄站立位膝关节正侧位X线片,评估KOA的严重程度(K-L分级)。根据双下肢骨骼长度差值将患者分为LLD组(差值>5 mm)和对照组(差值≤5 mm)。LLD组患者根据下肢的长度分为长腿侧和短腿侧。评估KOA患者LLD的发生率,比较LLD组和对照组性别、年龄、BMI及PTA值的差异。在LLD组中,采用Spearman相关性分析LLD大小与年龄、BMI和PTA的相关性。在LLD组,比较长腿侧与短腿侧AFTA、KOA K-L分级及已行TKA手术患者占比的差异。结果 141例KOA患者中,LLD患者68例,LLD的发生率为48.2%。LLD组PTA (3.93°±3.13°)大于对照组(2.31°±2.06°),差异有统计学意义(t=3.654,P<0.05)。在LLD组,短腿侧AFTA(4.74°±7.02°)大于长腿侧(2.0°±5.69°),短腿侧行TKA者占89.7%(61/68),高于长腿侧的57.4%(39/68),差异均有统计学意义(χ²=2.554、16.753, P值均<0.05),而短腿侧和长腿侧K-L分级之间差异无统计学意义(P＞0.05)。在LLD组,Spearman相关分析结果显示,LLD大小与PTA呈正相关,差异有统计学意义(r_s=0.547, P<0.01);而LLD大小与BMI、年龄之间无相关性,差异均无统计学意义(r_s=0.082、0.075,P值均＞0.05)。结论 原发性KOA患者LLD发生率较高,KOA多发生在短腿侧,LLD会导致骨盆倾斜,LLD差异程度越大,畸形越严重。早期积极干预可能对预防KOA有一定的意义。     

Placental insufficiency decreases cell cycle activity and terminal maturation in fetal sheep cardiomyocytes

Umbilicoplacental embolization (UPE) in sheep has been used to investigate the effects of placental insufficiency on fetal development. However, its specific effects on the heart have been little studied. The aim of this study was to determine the effects of placental insufficiency, induced by UPE, on cardiomyocyte size, maturation and proliferation. Instrumented fetal sheep underwent UPE for either 10 or 20 days. Hearts were collected at 125 ± 1 days (10 day group) or 136 ± 1 days (20 day group) of gestation (term ∼145 days). Cell size, maturational state (as measured by the proportion of binucleated myocytes) and cell cycle activity (as measured by positive staining of cells for Ki-67) were determined in dissociated cardiomyocytes. UPE fetuses were hypoxaemic, but mean arterial pressures were not different from controls. UPE fetuses were lighter than control fetuses (10 days: −21%, P < 0.05; 20 days: −27%, P < 0.01) and had smaller hearts, but heart weight was appropriate for body weight. Neither lengths nor widths were different between control and UPE cardiomyocytes at either age. Ten days of UPE did not significantly alter the proportion of binucleated myocytes or cell cycle activity in either ventricle. However, 20 days of UPE reduced cell cycle activity in both ventricles by ∼70% ( P < 0.05); the proportion of binucleated myocytes was also lower in UPE fetuses at this age (left ventricle: 31.1 ± 12.0 versus 46.0 ± 6.6%, P < 0.05; right ventricle: 29.4 ± 12.3 versus 46.3 ± 5.3%, P < 0.05). It is concluded that in the absence of fetal arterial hypertension, placental insufficiency is associated with substantially depressed growth of the heart through suppressed proliferation and maturation of cardiomyocytes.     

Ultrastructural evaluation of lung maturation in a sheep model of diaphragmatic hernia and tracheal occlusion

In fetuses with diaphragmatic hernia (DH) lung development is impaired, and pulmonary hypoplasia is one of the main factors responsible for the poor outcome of the disease. A possible treatment consists of occluding trachea during lung development to retain pulmonary fluid and to force the lung to expand. Although it appeared promising at first, this technique has recently been reported to decrease type II cell number and to induce surfactant deficiency. The aim of this study was to investigate lung maturation further through ultrastructural examination in a fetal lamb model of DH created at 85 d, followed or not by endoscopic balloon tracheal occlusion (TO) at 120 d of gestation. The proportion of alveolar epithelial type I and type II cells was altered by both treatments: the type I/type II cell ratio, which was about 2 in control lungs, was decreased 4.5-fold in DH lungs but was increased 4.5-fold in DH+TO lungs. The proportion of undifferentiated cells was increased in DH lungs. Indeterminate cells sharing features of type II and type I cells that were not observed in controls were seldom seen in DH lungs and were numerous in DH+TO lungs. The number of lamellar bodies per type II cell was decreased in both DH and DH+TO groups. In DH lungs, wall structure presented an immature appearance, with cellular connective tissue and poor secondary septation of saccules. In DH+TO lungs, primary septa appeared more mature, with reduced connective tissue, but secondary septa were still buds, although elastin was present at their tips. A single capillary layer was found in all three groups (control, DH, and DH+TO) with no sign of septal capillary pairing. This first investigation in DH and DH+TO lungs through transmission electron microscopy thus enabled us to show that compression and forced expansion of the lung are both responsible for alterations in type II cell differentiation and septal development.     

Aquaporin gene expression and regulation in the ovine fetal lung

Fetal lung development is dependent upon secretion of liquid into the future airways which must be cleared at birth to establish air-breathing. Aquaporins (AQP) 1, 3, 4 and 5 are membranous water channel proteins that are present in the lung after birth in rodents, with little expression before birth. Our aim was to describe the changes in AQP1, 3, 4 and 5 expression and protein levels in the fetal lung of a long-gestation species (sheep) and in response to physiological factors known to alter fetal lung liquid dynamics. Both mRNA and high protein levels were detected for AQP1, 3, 4 and 5 by day 100 (term is ≈150 days in ovine fetuses). A cortisol infusion (120–131 days) significantly (   P < 0.05  ) increased AQP1 (0.9 ± 0.2 (   n = 4  ) vs. 1.8 ± 0.3 (   n = 5  )) and AQP5 (8.8 ± 0.6 vs. 14.1 ± 1.2) mRNA levels in fetal lung (measured by real-time PCR). Ten days of tracheal obstruction significantly (   P < 0.05  ) decreased AQP5 mRNA levels (6.1 ± 0.9 (   n = 5  ) vs. 2.7 ± 0.3 (   n = 5  )). Immunohistochemistry was used to show that protein levels changed in parallel with the mRNA changes. These findings suggest that AQPs could be involved in lung liquid production and reabsorption during fetal development in long-gestation species.     

Glucocorticoids and hypothyroidism modulate development of fetal lung insulin receptors

We investigated the development of insulin receptors in membranes of fetal rabbit lung during normal ontogeny and the effect of glucocorticoids and hypothyroidism. Specific binding of 125I-insulin to fetal lung membranes increased progressively to a peak at 29 days gestation, declining by 30 days. Scatchard plots were curvilinear and revealed a progressive increase in receptor numbers (X 10(10)/mg protein) from 129 +/- 7 (mean +/- SE) at 22-24 days to 575 +/- 16 at 29 days, declining to 467 +/- 12 at 30 days, term being approximately 31 days. Affinities did not change throughout gestation and were similar to those of adult lung; receptor numbers in adults were significantly lower than in fetuses at 26-30 days. Epinephrine and PGE1 could evoke a doubling of cAMP production in adult and fetal lung membranes until 29 days. Concomitantly with the fall in fetal insulin receptor number at 30 days, cAMP production in response to epinephrine or PGE1 increased fivefold. Induction of fetal hypothyroidism decreased insulin receptor numbers in the lung of the 28-day fetus by 70% from control (P less than 0.001) without a change in receptor affinity. In contrast, betamethasone administration increased fetal lung insulin receptor numbers by 250% (P less than 0.001) but did not alter their affinity; maternal lung insulin receptors were not altered. Thus, normal ontogeny of the fetal lung insulin receptor is characterized by a progressive increase in number followed by decline immediately before parturition associated with a sharp increase of cAMP responsiveness of the membranes. Hypothyroidism and glucocorticoid exposure can modulate the normal development of the fetal lung insulin receptor.     

T-cadherin (CDH13, H-cadherin) expression downregulated surfactant protein D in bronchioloalveolar cells

T cadherin is a unique cadherin cell adhesion molecule that is anchored to the surface membrane through a glycosyl phosphatidyl inositol (GPI) moiety. In the present study, we postulated that T cadherin could regulate surfactant protein (SP)-D gene expression in human bronchioloalveolar type-II cells. We transfected A549 cells (human lung cancer cell line with alveolar type-II cell characteristics) with the T-cadherin expression vector. Both original and control plasmid-transfected A549 cells expressed SP-D; however, neither human nor murine T-cadherin-transfected A549 cells expressed SP-D mRNA. The downregulation of SP-D production in human T-cadherin-expressed A549 cells was also demonstrated using Western immunoblotting techniques. Control vector-transfected A549 cells showed a positive band of SP-D but not of T cadherin. In contrast, T-cadherin-transfected A549 cells, which expressed T-cadherin protein, did not produce SP-D. We further examined the relationship of T cadherin and SP-D expression in secondary pulmonary alveolar proteinosis associated with hematolymphoid malignancies. SP-D was detected in bronchioloalveolar type-II cells in alveolar proteinosis. However, little or no T-cadherin expression was detected in alveolar type-II cells in these patients. To our knowledge, this is the first report describing an effect of cadherin on SP production in bronchioloalveolar cells.     

Differential expression of coxsackievirus and adenovirus receptor on alveolar epithelial cells between fetal and adult mice determines their different susceptibility to coxsackievirus B infection

Coxsackievirus B (CVB) can cause aseptic meningitis, myocarditis and respiratory disease, especially in newborn infants. To compare the susceptibility to CVB infection of fetal and adult mice, we prepared primary alveolar epithelial cells (AECs) from lungs of BALB/c mice. In contrast to fetal mouse AECs, those of adults were less susceptible to CVB3 infection, as indicated by decreased cytopathic effects, and reduced levels of viral particles bound at the cell surface. In adult mouse AECs, amplification of the viral genome and virus capsid protein VP1 synthesis were concomitantly reduced. In addition, the cell-surface expression of coxsackievirus and adenovirus receptor (CAR), which plays a key role in the initiation of CVB and pulmonary infection, was downregulated in adult mouse AECs. These findings demonstrate that adult mouse AECs are less susceptible to CVB3 due to decreased CAR levels. Thus, these findings strongly indicate that the level of virus receptors on AECs is one of the crucial determinants for the age-dependence of CVB virulence in the mouse lung.     

谷氨酰胺缺乏对急性早幼粒白血病原代细胞生长和分化的影响

目的:了解谷氨酰胺(Gln)缺乏对急性早幼粒白血病(APL)原代细胞生长和分化的影响。方法:从18例未经治疗的APL病人外周血中提取APL原代细胞,在无Gln的RPMI1640培养液中补加10%胎牛血清,以活细胞密度5×10⁸/L接种细胞,在37℃,5%CO2和饱和湿度下培养4d,计数活细胞,并收集细胞行Wright-Giemsa、DNA、POX、NAE及NaF抑制试验、墨汁吞噬试验和NBT还原试验等细胞化学染色,于油镜下观察。结果:经4d培养,其活细胞密度为起始活细胞密度的(54.28±4.28)%,而对照组为(108.56±12.27)%(P<0.01);成熟分叶核粒细胞和杆状粒细胞比例显著高于对照组(P<0.01)。结论:缺乏Gln可使APL原代细胞生长受到抑制,并可使之向成熟粒细胞方向分化。     

Lung growth response after tracheal occlusion in fetal rabbits is gestational age-dependent.

In utero tracheal occlusion (TO) is a potent stimulus of fetal lung growth, and is currently being applied in clinical trials to treat severe forms of pulmonary hypoplasia. The aim of this study was to examine the effect of timing of TO on pulmonary growth and maturation rates. Fetal rabbits (term = 31 d) were subjected to in utero tracheal clipping at 24 (late pseudoglandular stage) or 27 d of gestation (late canalicular/early terminal sac stage). Sham-operated littermates served as controls (C). Animals were killed at time intervals ranging from 1 to 6 d (early group) or 1 to 3 d (late group) after occlusion. Lung growth was measured by computerized stereologic volumetry and 5'-bromo-2'-deoxyuridine (BrdU) pulse labeling. Pneumocyte II population kinetics were analyzed using a combination of anti-surfactant protein-A and BrdU immunohistochemistry and computer-assisted morphometry. Statistical analysis was performed using unpaired Student's t test. Early TO was followed by an initial 3-d stagnation of growth and subsequently a dramatic acceleration of growth (BrdU-labeling index [LI] 10.1 +/- 0. 6% in TO versus 2.7 +/- 0.5% in C at 29 d, P < 0.001). In contrast, late TO induced an immediate and sustained moderate increase of lung growth (BrdU-LI 2.8 +/- 0.9% in TO versus 1.1 +/- 0.2% in C at 30 d, P < 0.05), associated with relatively more pronounced air-space distension. Whereas late TO caused no significant alterations in type II cell density or proliferation, early TO was followed by a marked increase in type II cell proliferation, paradoxically associated with dramatic reduction of type II cell density after 29 d. The effects of intrauterine TO on fetal lung growth and type II cell kinetics critically depend on the gestational age, and thus on the maturity of the lungs at the time of surgery. These findings have important clinical implications with respect to the timing of fetal interventions aimed at promoting lung growth. The fetal rabbit provides an invaluable model to study the mechanics and age dependency of TO-induced lung growth.     

Correlation of lung macrophage age and surface antigen in the hamster

A monoclonal antibody specific for a surface antigen found on hamster lung macrophages has been produced. Macrophages obtained from LSH Syrian golden hamsters by pulmonary lavage have varying amounts of this antigen on their surface. We compared the age of alveolar macrophages (using 3H-thymidine) with the amount of surface antigen. Lung macrophages were obtained by repeated saline lavage at 1, 3, 5, and 10 days after 3H-thymidine injection. Monoclonal antibody was then reacted with these cells followed by fluorescein isothiocyanate-conjugated protein A. Cell size and fluorescence were analyzed by flow cytometry. A wide range of fluorescent intensity was observed; the cells were sorted into four subpopulations (SPs). SP1 had the lowest fluorescence per cell, and SP4 had the highest. The sorted cells were placed on glass slides, and autoradiographs were made. The percentage of labeled macrophages in each SP was determined. At 1 day after thymidine injection, cells with a paucity of antigen (SP1) were the most highly labeled; 12.5% of SP1 macrophages were labeled, but only 1.4 and 1.1% of SP3 and SP4 were labeled, respectively. The labeling was relatively even in all four SPs at 3 days, but at 5 days the labeling of cells in SP2 and SP3 was highest. By day 10, labeled macrophages had large amounts of surface antigen and were in SP3 and SP4. These findings suggest that pulmonary macrophages that have recently synthesized DNA lack surface antigen. As time passes, cells mature and more antigen is acquired. The amount of surface antigen reflects cell age and provides a useful tool to isolate and study macrophage SPs.     

维生素C对CD4+效应记忆性T细胞体外扩增的影响

 目的：探讨小分子药物维生素C（VC）对CD4+效应记忆性T细胞（TEM）体外扩增的影响从而改善过继免疫治疗的效果。方法：体外分离正常人的外周血CD4+ T淋巴细胞,将细胞分为2组（实验组和对照组）进行细胞培养。实验组加入VC后,通过细胞计数仪和流式细胞仪对2组细胞中TEM的扩增情况进行检测。结果：(1) 在CD4+ T细胞体外扩增实验中,VC对CD4+ T细胞的总数无显著影响。(2) VC使TEM在CD4+ T细胞中的比例显著升高,100 mg/L为扩增的最佳浓度。(3) 在CD4+ T细胞扩增的第10天检测其中TEM的细胞数量,对照组TEM的数量为(1.22±0.15)×106,实验组TEM的数量为(3.56±0.35)×106 ,两者的差异有统计学意义（P<0.01）。结论: VC可有效地促进CD4+ TEM的体外扩增,为过继免疫治疗提供简单、安全及有效的体外扩增方法。     

Neurotrophic ACTH analogue promotes plasticity of type I corticosteroid receptor in brain of senescent male rats

Age-related changes were studied in the concentration of type-I and type-II corticosteroid receptors in the hippocampus of young adult (3 months) and aged (28.5 to 30.5 months) male rats. Using 3H-labelled ligands, in vitro binding of type-I and type-II corticosteroid receptors in the soluble cell fraction (cytosol) revealed an age-related decrease in concentration of both receptor types of 52% and 28%, respectively. Infusion of young and aged male rats for 2 weeks with the ACTH4-9 [adrenocorticotropin4-9] peptide analogue ORG 2766 (0.5 micrograms/0.5 microliter/hr) resulted in only a minor increase (+8%) in the number of type-I receptors in young rats. In the aged animals, however, the type-I receptor concentration was 68% higher than in the vehicle-treated aged animals. In contrast, no effect of the peptide treatment was noted on the concentration of type-II receptors in either young or aged rats. Furthermore, no effect was found for either age or treatment with peptide on the affinity of type-I and type-II receptors for their respective ligands. Binding of 3H-labelled ligands to brain sections of young and aged rats was performed using in vitro autoradiography. Quantitative image analysis of the film showed that in senescence there is a marked reduction in both type-I (62-75%) and type-II (29-56%) receptor concentrations in the hippocampal subregions (CA1, CA2, CA3 and dentate gyrus) as well as in the lateral septum. Treatment of aged rats with ORG 2766 selectively reversed the age-associated reduction in type-I receptors, while the peptide did not affect the type-II receptors.(ABSTRACT TRUNCATED AT 250 WORDS)     

肾上腺髓质素m RNA在慢性缺氧大鼠右心室中的表达

目的:探讨肾上腺髓质素(AM)在慢性低氧性肺动脉高压发病中的作用。方法:16只大鼠随机分为低氧组和对照组,间断常压低氧14d复制肺动脉高压模型,静脉右心导管测定右室收缩压(RVSP)的变化,分离心室检测右室/(左室+室间隔)(RV/LV+SP)比值,原位杂交法检测AMmRNA在右心室中的表达。结果:低氧组大鼠右室压为(63.63±3.42)mmHg,显著高于对照组的(34.13±3.40)mmHg(P<0.01)。低氧组大鼠(RV/LV+SP)比值为0.439±0.039,显著高于对照组的0.23±0.025(P<0.01)。AMmRNA在对照组大鼠的右室心肌细胞也有少量表达,低氧组大鼠其表达显著多于对照组。图像分析表明,低氧组的平均吸光度、平均表达面积分别为0.1061±0.0188,0.1421±0.0165,均显著高于对照组的0.0872±0.0171,0.0967±0.0135。结论:低氧时右心室AMmRNA表达增加,提示可能在肺动脉高压的发病中起保护作用。     

Essential roles for angiotensin receptor AT1a in bleomycin-induced apoptosis and lung fibrosis in mice

Apoptosis of alveolar epithelial cells (AECs) has been implicated as a key event in the pathogenesis of lung fibrosis. Recent studies demonstrated a role for the synthesis and binding of angiotensin II to receptor AT1 in the induction of AEC apoptosis by bleomycin (BLEO) and other proapoptotic stimuli. On this basis we hypothesized that BLEO-induced apoptosis and lung fibrosis in mice would be inhibited by the AT1 antagonist losartan (LOS) or by targeted deletion of the AT1 gene. Lung fibrosis was induced by intratracheal administration of BLEO (1 U/kg) to wild-type C57BL/6J mice. Co-administration of LOS abrogated BLEO-induced increases in total lung caspase 3 activity detected 6 hours after in vivo administration and reduced by 57% BLEO-induced caspase 3 activity in blood-depleted lung explants exposed to BLEO ex vivo (both P < 0.05). Co-administration of LOS in vivo reduced DNA fragmentation and immunoreactive caspase 3 (active form) in AECs, measured at 14 days after intratracheal BLEO, by 66% and 74%, respectively (both P < 0.05). LOS also inhibited the accumulation of lung hydroxyproline by 45%. The same three measures of apoptosis and lung fibrosis were reduced by 89%, 85%, and 75%, respectively (all P < 0.01), in mice with a targeted disruption of the AT1a receptor gene (C57BL/6J-Agtr1a(tm1Unc)). These data indicate an essential role for angiotensin receptor AT1a in the pathogenesis of BLEO-induced lung fibrosis in mice and suggest that AT1 receptor signaling is required for BLEO-induced apoptosis of AECs in mice as it is in rat and human AECs.     

基于髋关节数字解剖降低THA术后下肢不等长带刻度股骨髓腔锉和相应股骨柄假体及技术的研发与应用

目的 根据髋关节的数字解剖特点研发一种带刻度股骨髓腔锉和相应股骨柄假体及测量方法,探讨其在全髋关节置换手术（THA）中控制下肢长度的效果,并对影响其使用效果的原因进行分析。方法 回顾性队列研究。纳入2017年6月—2020年7月山东省千佛山医院行初次单侧THA的患者300例。其中,男154例、女146例,年龄27~86（59.5±11.3）岁。按照术中控制下肢长度的方法进行分组：观察组134例,采用带刻度髓腔锉控制下肢长度;对照组166例,采用徒手方法控制下肢长度。观察指标：（1）比较2组患者性别、身高、术前下肢不等长（LLD）、手术侧别等基线资料。（2）测量和比较2组患者术后LLD的差异,以及LLD的分布情况。（3）比较2组LLD>10 mm患者的占比,分析导致患者术后LLD>10 mm的原因。结果 所有患者手术过程顺利,术后切口均为一期愈合。（1）2组患者性别、身高、术前LLD、手术侧别等基线资料比较,差异均无统计学意义（P值均>0.05）。（2）观察组患者术后LLD为4.76（2.98,7.18）mm,对照组为5.85（3.78,8.38）mm,差异有统计学意义（Z=-2.84,P=0.004）;观察组患者术后LLD的分布情况优于对照组,差异有统计学意义（Z=3.08,P=0.002）。（3）观察组中有8例（5.97%,8/134）患者术后LLD>10 mm,对照组有24例（14.46%,24/166）,差异有统计学意义（χ²=5.61,P=0.018）;术后LLD>10 mm原因分析：与假体和患者不匹配有关（观察组3例、对照组4例）;与髋臼下缘骨赘增生明显导致克氏针定位偏下有关（观察组5例、对照组3例）。结论 在行单侧THA时,使用带刻度股骨髓腔锉相比徒手方法可以更有效地控制术后LLD。而假体不匹配以及术中对髋臼下缘及大转子顶点探查不够准确是影响该方法有效控制LLD的主要原因。     

Altered epithelial cell proportions in the fetal lung of glucocorticoid receptor null mice

Glucocorticoids provide important signals for maturation of the fetal lung and antenatal glucocorticoids are used to reduce the respiratory insufficiency suffered by preterm infants. To further understand the role of glucocorticoids in fetal lung maturation, we have analyzed mice with a targeted null mutation for the glucocorticoid receptor (GR) gene, which severely retards lung development. The lungs of fetal GR-null mice have increased lung weight and DNA content, are condensed and hypercellular, with reduced septal thinning leading to a 6-fold increase in the airway to capillary diffusion distance. In fetal GR-null mice, mRNA levels of the type II epithelial cell surfactant protein genes A and C were reduced by approximately 50%. Analysis of epithelial cell types by electron microscopy revealed that the proportions of type II cells were increased by approximately 30%, whereas the proportions of type-I cells were markedly reduced (by approximately 50%). Similarly, we found a 50% reduction in mRNA levels for T1alpha and aquaporin-5, two type I cell-specific markers, and a 20% reduction in aquaporin-1 mRNA levels. This demonstrates that during murine embryonic development, receptor-mediated glucocorticoid signaling facilitates the differentiation of epithelial cells into type I cells, but is not obligatory for type II cell differentiation.