市售长叶松油和锡兰肉桂油对登革热媒蚊埃及伊蚊的灭幼效果(英文)

松油和桂皮油由于具有芳香性气味, 因而成为良好的成虫驱避剂, 但是关于它们对蚊虫的杀幼虫作用研究不多。为揭示市售的长叶松Pinus longifolia油和锡兰肉桂Cinnamomum zeylanicum油对来源于印度德里的埃及伊蚊Aedes aegypti 4龄幼虫的毒杀潜力, 我们进行了室内研究, 以幼虫死亡率及行为改变和形态改变等指标评估其杀幼虫潜力。结果表明： 两种油对埃及伊蚊4龄幼虫均具有毒杀作用, 且松油的灭幼效果优于桂皮油。松油的LC₅₀和LC₇₀ 值分别为0.33093 mg/L 和0.54476 mg/L, 而桂皮油的LC₅₀和LC₇₀ 值分别为0.63159 mg/L和0.77736。进一步观察发现, LC₉₀剂量下桂皮油的杀幼虫潜力强于松油, 其LC₉₀为1.11879 mg/L, 而松油的LC₉₀为 1.04915 mg/L。在处理的幼虫中观察到行为改变, 如兴奋、 坐立不安、 颤抖、 痉挛然后瘫痪, 说明这两种油可能对其神经肌肉系统产生了影响。显微观察处理幼虫的形态改变发现, 与对照相比, 大多数器官的外观正常, 只是肛鳃略为内收缩而引起结构畸形, 提示肛腮可能是这两种油的作用位点, 腮的功能异常引起了幼虫死亡。这两种油品可开发用作防治蚊虫的新型杀幼虫药剂。     

2种中草药对福寿螺的杀灭效果及对肝脏影响

【目的】有效控制福寿螺产生的危害,为实现中草药的资源化利用提供依据。【方法】以甘草、陈皮为植物源灭螺剂,进行不同浓度梯度(0、0.5、1.5、3.0、4.5、6.0 g·L^-1)提取液浸泡下的灭螺活性探究。【结果】甘草组、陈皮组处理下福寿螺死亡率随时间的增长在不同浓度下毒杀效果明显。对48 h时福寿螺死亡率数据进行概率单位法回归分析,发现甘草组(LC₂₅、LC₅₀、LC₇₅)<陈皮组(LC₂₅、LC₅₀、LC₇₅),说明福寿螺对甘草更敏感。为进一步探究福寿螺死亡原因,在前期研究的基础上深入探讨甘草、陈皮提取液对福寿螺的肝脏的影响,在亚致死浓度甘草0.511 g·L^-1(LC₂₅)、0.940 g·L^-1(LC₅₀)、1.727 g·L^-1(LC₇₅)和陈皮3.892 g·L^-1...     

叔丁基对羟基茴香醚和诺氟沙星对水生生物的影响

采用急性毒性试验的方法,研究了叔丁基对羟基茴香醚(Butylated hydroxyanisole,BHA)和诺氟沙星(Norfloxacin,NFLX)对水生生物斜生栅藻和大型溞的毒性效应。结果表明大型溞在BHA和NFLX暴露下48h的LC₅₀分别为3.15mg·L^-1和194.98mg·L^-1。BHA和NFLX对斜生栅藻也有明显的毒性作用,其96h的EC₅₀分别为6.19mg·L^-1和50.18mg·L^-1。大型蚤对BHA暴露的敏感性强于斜生栅藻,而斜生栅藻对NFLX的敏感性比大型溞强。根据化学物质对鱼类和溞类的毒性评价标准,BHA和NFLX分别属于中等和低等毒性的化合物。     

α-萜品醇熏蒸对大麦虫体内抗氧化酶活性的影响

为研究植物挥发性有机化合物α-萜品醇的杀虫活性及作用机理, 本研究采用熏蒸法测定了α-萜品醇对大麦虫Zophobas morio（鞘翅目： 拟步行甲科）4龄幼虫的急性毒性, 并测定了不同熏蒸时间后幼虫体内超氧化物歧化酶（SOD）、 过氧化物酶（POD）和过氧化氢酶（CAT）活性。结果表明： 熏蒸48 h时, α-萜品醇对大麦虫4龄幼虫的LC₅₀和LC₂₀值分别为69.425 μg/L和59.916 μg/L。α-萜品醇（LC₂₀和LC₅₀）处理的4龄幼虫SOD, POD和CAT活性均表现为先升高后降低的趋势。据此推测, α-萜品醇在幼虫体内积累显著影响幼虫体内SOD, POD和CAT活性, 降低虫体内自由基的清除能力, 从而对其产生毒害作用。     

氨对褶纹冠蚌钩介幼虫及稚蚌的急性毒性

为探究氨对蚌类早期生活史阶段的毒性效应,研究分别以褶纹冠蚌(Cristaria plicata)的钩介幼虫及稚蚌为实验对象开展了24h和48h的急性毒性实验。结果表明:氨对褶纹冠蚌钩介幼虫的24h半致死浓度(LC₅₀)为0.63 mg NH₃-N/L (NH₃,分子氨)和78 mg TAN_7.0,20℃/L (TAN_7.0,20℃,pH 7.0水温20℃时即标准化的总氨氮);氨对褶纹冠蚌稚蚌的48h LC₅₀为0.60 mg NH₃-N/L和104 mg TAN_7.0,20℃/L;上述阈值高于已有研究中氨对其他淡水蚌类的毒性阈值;褶纹冠蚌钩介幼虫对氨氮的耐受性低于稚蚌,二者均低于幼蚌,因此褶纹冠蚌更早期生活史阶段对氨的耐受性更低。相关研究结果可完善氨对蚌类毒性的理解,为水体氮管理策略的制定和蚌类保护提供一定科学依据。     

低致死剂量氯虫苯甲酰胺对沟金针虫食物利用和相关生理生化指标的剂量和时间效应

【目的】明确氯虫苯甲酰胺对沟金针虫Pleonomus canaliculatus亚致死效应的生理生化机制,阐明氯虫苯甲酰胺低致死剂量对沟金针虫食物利用、能量物质含量以及体内消化酶、保护酶和解毒酶活力的影响。【方法】室内采用土壤混药法测定氯虫苯甲酰胺对沟金针虫3龄幼虫毒力,并测定了氯虫苯甲酰胺LC₁₀, LC₂₅和LC₄₀低致死剂量对沟金针虫3龄幼虫营养指标和体内能量物质含量的影响;采用酶动力学法检测了氯虫苯甲酰胺低致死剂量处理1, 6, 12, 24, 48和72 h后沟金针虫3龄幼虫体内消化酶(蛋白酶、α-淀粉酶、脂肪酶、海藻糖酶)、保护酶(CAT, POD和SOD)以及解毒酶(CarE, MFO和GST)活力的动态变化。【结果】氯虫苯甲酰胺对沟金针虫3龄幼虫有较高毒力,其LC₅₀值为1.2397 mg/kg。LC₁₀和LC₄₀剂量氯虫苯甲酰胺处理沟金针虫3龄幼虫后,平均相对生长率(MRGR)和近似消化率(AD)显著降低,严重干扰其对食物的利用;LC₁₀, LC₂₅和LC₄₀剂量处理后沟金针虫3龄幼虫体内主要的能量物质(蛋白质、脂质、碳水化合物、海藻糖)含量和消化酶活力均明显降低,而解毒酶和保护酶活力显著增加,最终延缓其生长发育。【结论】氯虫苯甲酰胺对沟金针虫幼虫具有很高的杀虫活性,低致死剂量氯虫苯甲酰胺处理沟金针虫幼虫后,通过抑制消化酶活性,使其对食物的利用能力降低和生长发育延缓,以及诱导解毒酶和保护酶活性来阻止外界毒物侵害。研究结果为阐明氯虫苯甲酰胺对沟金针虫的亚致死效应机制及作用机理提供了一定的理论基础。     

用山苍子芳香油防治蚕豆象

用山苍子芳香油拌种防治蚕豆象成虫Bruchus rufimanus Boheman每50公斤蚕豆拌油300克两,12天后成虫死亡率达95.8%。在22—28℃下,用200ml/m³的山苍子油薰蒸8天,成虫死亡率达100%,其LC₅₀为59.6ml/m³,LC₉₅为134.9ml/m³。3月份在20℃下,山苍子油薰蒸成虫的LT₅₀为177.8小时,LT₉₅为707.9小时;在25℃下薰蒸,LT₅₀为86.6小时,LT₉₅为334.9小时;在30℃下薰蒸,LT₅₀为50.1小时,LT₉₅为141.2小时;在36℃下薰蒸,不到24小时成虫即全死。山苍子油毒杀幼虫的效果较差。此油平时可供人们药用和食用,也不影响蚕豆发芽。     

亚致死浓度氯虫苯甲酰胺可降低亚洲玉米螟的种群增长

为了探讨氯虫苯甲酰胺对亚洲玉米螟Ostrinia furnacalis (Guenée)的抗性风险评估, 为科学使用氯虫苯甲酰胺防治亚洲玉米螟提供理论基础, 本研究在实验室条件下采用饲料混毒法测定了新型杀虫剂氯虫苯甲酰胺对亚洲玉米螟的毒力, 利用生命表技术研究了氯虫苯甲酰胺对亚洲玉米螟 3龄幼虫的亚致死效应。结果表明： 氯虫苯甲酰胺对亚洲玉米螟3龄幼虫的LC₁₀, LC₄₀ 和LC₅₀分别为0.038, 0.098 和0.123 mg a. i. /L。以氯虫苯甲酰胺LC₁₀和LC₄₀剂量分别处理亚州玉米螟3龄幼虫后, 幼虫和蛹的发育历期明显延长, 成虫寿命缩短, 产卵量也显著降低, 但对蛹重（雌： P=0.337, 雄： P=0.121）、卵孵化率（P=0.087）和性比（P=0.379）无显著影响。处理种群的净增值率（R₀）、内禀增长率（r_m）和周限增长率（λ）显著低于对照种群（P<0.0001）。结果提示, 氯虫苯甲酰胺的亚致死浓度可降低亚洲玉米螟的种群增长。     

冬青油与肉桂油对淡色库蚊的生物活性

为进一步明确冬青油（wintergreen oil）与肉桂油（cinnamon oil）对蚊虫的生物活性, 本研究采用浸液法、 “Y”型嗅觉仪法和密闭三角瓶熏蒸法, 分别测定了两种精油对淡色库蚊Culex pipiens pallens幼虫的毒杀作用以及对成虫的驱避和熏杀活性。结果显示： 肉桂油和冬青油对淡色库蚊幼虫均具有较强的毒杀作用, 处理24 h的LC₅₀分别为71.87 mg/L和 102.83 mg/L。在0.5 μL的供试剂量下, 冬青油与肉桂油在20 min内对淡色库蚊的驱避率均在80%以上, 显示了较好的驱蚊活性。冬青油对淡色库蚊具有明显的熏蒸击倒作用, 12 μL/L浓度下的KT₅₀为3.97 min; 而肉桂油则具有较好的熏蒸致死活性, 熏蒸5 h的LC₅₀ 为0.31 μL/L。冬青油与肉桂油按1∶1体积比混配后对淡色库蚊表现出较好的击倒和致死效果。冬青油和肉桂油既对淡色库蚊幼虫具有较强的毒杀作用, 又对淡色库蚊雌成虫表现出较好的驱避和熏杀活性, 具有开发成为植物源蚊虫防控剂的潜力。     

溴氰虫酰胺亚致死剂量对甜菜夜蛾生长发育及体内解毒酶活性的影响

【目的】探讨溴氰虫酰胺对甜菜夜蛾 Spodoptera exigua (Hübner)的亚致死效应,为甜菜夜蛾的综合防治和溴氰虫酰胺的合理使用提供理论依据。【方法】采用饲料混毒法,测定溴氰虫酰胺对甜菜夜蛾3龄幼虫的毒力,确定其亚致死剂量（LC₁₀和LC₂₅）,并分别用该亚致死剂量处理甜菜夜蛾3龄幼虫,研究其对甜菜夜蛾的生长发育和体内3种解毒酶活性的影响。【结果】以LC₁₀ 和LC₂₅剂量处理甜菜夜蛾3龄幼虫后,幼虫生长受到显著抑制,虫重抑制率分别为11.55%和27.68%;LC₁₀和LC₂₅处理组3龄幼虫到化蛹天数分别比对照组延长0.07和0.20 d;化蛹率显著低于对照组（80.93%）,分别为63.89%和49.43%;成虫寿命显著缩短1.11 d和2.08 d;单雌产卵量和卵孵化率也低于对照组。亚致死剂量溴氰虫酰胺处理甜菜夜蛾幼虫后24-96 h,羧酸酯酶活性和谷胱甘肽-S转移酶活性表现出相似的变化趋势,呈先激活升高、后被抑制降低;而多功能氧化酶活性在药剂处理48 h和72 h均受到不同程度的抑制作用,这种抑制作用与浓度成正比。【结论】亚致死剂量的溴氰虫酰胺对甜菜夜蛾的生长发育有显著抑制作用,对其幼虫体内解毒酶活性也有不同程度的抑制作用。     

Phoenixin-14 stimulates differentiation of 3T3-L1 preadipocytes via cAMP/Epac-dependent mechanism

Phoenixin-14 (PNX) is a newly discovered peptide produced by proteolytic cleavage of the small integral membrane protein 20 (Smim20). Previous studies showed that PNX is involved in controlling reproduction, pain, anxiety and memory. Furthermore, in humans, PNX positively correlates with BMI suggesting a potential role of PNX in controlling fat accumulation in obesity. Since the influence of PNX on adipose tissue formation has not been so far demonstrated, we investigated the effects of PNX on proliferation and differentiation of preadipocytes using 3T3-L1 and rat primary preadipocytes. We detected Smim20 and Gpr173 mRNA in 3T3-L1 preadipocytes as well as in rat primary preadipocytes. Furthermore, we found that PNX peptide is produced and secreted from 3T3-L1 and rat primary adipocytes. PNX increased 3T3-L1 preadipocytes proliferation and viability. PNX stimulated the expression of adipogenic genes (Pparγ, C/ebpβ and Fabp4) in 3T3-L1 adipocytes. 3T3-L1 preadipocytes differentiated in the presence of PNX had increased lipid content. Stimulation of cell proliferation and differentiation by PNX was also confirmed in rat preadipocytes. PNX failed to induce AKT phosphorylation, however, PNX increased cAMP levels in 3T3-L1 cells. Suppression of Epac signalling attenuated PNX-induced Pparγ expression without affecting cell proliferation. Our data show that PNX stimulates differentiation of 3T3-L1 and rat primary preadipocytes into mature adipocytes via cAMP/Epac-dependent pathway. In conclusion our data shows that phoenixin promotes white adipogenesis, thereby may be involved in controlling body mass regulation.     

Premetazoan Origin of Neuropeptide Signaling

Neuropeptides are a diverse class of signaling molecules in metazoans. They occur in all animals with a nervous system and also in neuron-less placozoans. However, their origin has remained unclear because no neuropeptide shows deep homology across lineages, and none have been found in sponges. Here, we identify two neuropeptide precursors, phoenixin (PNX) and nesfatin, with broad evolutionary conservation. By database searches, sequence alignments, and gene-structure comparisons, we show that both precursors are present in bilaterians, cnidarians, ctenophores, and sponges. We also found PNX and a secreted nesfatin precursor homolog in the choanoflagellate Salpingoeca rosetta. PNX, in particular, is highly conserved, including its cleavage sites, suggesting that prohormone processing occurs also in choanoflagellates. In addition, based on phyletic patterns and negative pharmacological assays, we question the originally proposed GPR-173 (SREB3) as a PNX receptor. Our findings revealed that secreted neuropeptide homologs derived from longer precursors have premetazoan origins and thus evolved before neurons.     

Phoenixin-14 stimulates proliferation and insulin secretion in insulin producing INS-1E cells

Phoenixin (PNX) is a recently discovered neuropeptide which modulates appetite, pain sensation and neurons of the reproductive system in the central nervous system. PNX is also detectable in the circulation and in peripheral tissues. Recent data suggested that PNX blood levels positively correlate with body weight as well as nutritional status suggesting a potential role of this peptide in controlling energy homeostasis. PNX is detectable in endocrine pancreas, however it is unknown whether PNX regulates insulin biosynthesis or secretion. Using insulin producing INS-1E cells and isolated rat pancreatic islets we evaluated therefore, whether PNX controls insulin expression, secretion and cell proliferation. We identified PNX in pancreatic alpha as well as in beta cells. Secretion of PNX from pancreatic islets was stimulated by high glucose. PNX stimulated insulin mRNA expression in INS-1E cells. Furthermore, PNX enhanced glucose-stimulated insulin secretion in INS-1E cells and pancreatic islets in a time-dependent manner. Stimulation of insulin secretion by PNX was dependent upon cAMP/Epac signalling, while potentiation of cell growth and insulin mRNA expression was mediated via ERK1/2- and AKT-pathway. These results indicate that PNX may play a role in controlling glycemia by interacting with pancreatic beta cells.     

Age-dependent decline in mouse lung regeneration with loss of lung fibroblast clonogenicity and increased myofibroblastic differentiation

While aging leads to a reduction in the capacity for regeneration after pneumonectomy (PNX) in most mammals, this biological phenomenon has not been characterized over the lifetime of mice. We measured the age-specific (3, 9, 24 month) effects of PNX on physiology, morphometry, cell proliferation and apoptosis, global gene expression, and lung fibroblast phenotype and clonogenicity in female C57BL6 mice. The data show that only 3 month old mice were fully capable of restoring lung volumes by day 7 and total alveolar surface area by 21 days. By 9 months, the rate of regeneration was slower (with incomplete regeneration by 21 days), and by 24 months there was no regrowth 21 days post-PNX. The early decline in regeneration rate was not associated with changes in alveolar epithelial cell type II (AECII) proliferation or apoptosis rate. However, significant apoptosis and lack of cell proliferation was evident after PNX in both total cells and AECII cells in 24 mo mice. Analysis of gene expression at several time points (1, 3 and 7 days) post-PNX in 9 versus 3 month mice was consistent with a myofibroblast signature (increased Tnc, Lox1, Col3A1, Eln and Tnfrsf12a) and more alpha smooth muscle actin (αSMA) positive myofibroblasts were present after PNX in 9 month than 3 month mice. Isolated lung fibroblasts showed a significant age-dependent loss of clonogenicity. Moreover, lung fibroblasts isolated from 9 and 17 month mice exhibited higher αSMA, Col3A1, Fn1 and S100A expression, and lower expression of the survival gene Mdk consistent with terminal differentiation. These data show that concomitant loss of clonogenicity and progressive myofibroblastic differentiation contributes to the age-dependent decline in the rate of lung regeneration.     

Adaptation of respiratory muscle perfusion during exercise to chronically elevated ventilatory work.

Pneumonectomy (PNX) leads to chronic asymmetric ventilatory loading of respiratory muscles (RM). We measured RM energy requirements during exercise from RM blood flow (Q) using a fluorescent microsphere technique in dogs that had undergone right PNX as adults (adult R-PNX) or as puppies (puppy R-PNX), compared with dogs subjected to right thoracotomy without PNX as puppies (Sham) and to left PNX as adults (adult L-PNX). Ventilatory work (W) was measured during exercise. RM weight was determined post mortem. After adult and puppy R-PNX, the right hemidiaphragm becomes grossly distorted, but W and right costal muscle mass increased only after adult R-PNX. After adult L-PNX, the diaphragm was undistorted; W and left hemidiaphragm RM Q were elevated, but muscle mass did not increase. Mass of parasternal muscle did not increase after adult R-PNX, despite increased Q. Thus muscle mass increased only in response to the combination of chronic stretch and dynamic loading. There was a dorsal-to-ventral gradient of increasing Q within the diaphragm, but the distribution was unaffected by anatomic distortion, hypertrophy, or workload, suggesting a fixed pattern of neural activation. The diaphragm and parasternals were the primary muscles compensating for the asymmetric loading from PNX.     

Regional lung growth following pneumonectomy assessed by computed tomography.

After pneumonectomy (PNX), mechanical strain on the remaining lung is greatly increased. To assess whether remaining lobes expand uniformly after left or right PNX (removing 42 and 58% of lung mass, respectively), we performed high-resolution computed tomography (CT) scans at 45 ml/kg above end-expiratory lung volume on adult male foxhounds after left or right PNX, which were compared with adult Sham controls. Air and tissue volumes were separately measured in each lobe. After left PNX, air and tissue volumes in the right upper and cardiac lobes increased approximately 2.2-fold above and below the heart, whereas volumes in right middle and lower lobes did not change significantly. After right PNX, air and tissue volumes in the left upper and middle lobes increased 2.3- to 2.7-fold across the midline anterior to the heart, whereas the left lower lobe expanded approximately 1.9-fold posterior to the heart. Regional changes in volume density of tissue post-PNX estimated by CT scan parallel postmortem estimates by morphometric analyses. Data indicate heterogeneous regional distribution of mechanical lung strain, which could influence the differential cellular compensatory response following right and left PNX.     

Endothelial-derived angiocrine signals induce and sustain regenerative lung alveolarization

To identify pathways involved in adult lung regeneration, we employ a unilateral pneumonectomy (PNX) model that promotes regenerative alveolarization in the remaining intact lung. We show that PNX stimulates pulmonary capillary endothelial cells (PCECs) to produce angiocrine growth factors that induce proliferation of epithelial progenitor cells supporting alveologenesis. Endothelial cells trigger expansion of cocultured epithelial cells, forming three-dimensional angiospheres reminiscent of alveolar-capillary sacs. After PNX, endothelial-specific inducible genetic ablation of Vegfr2 and Fgfr1 in mice inhibits production of MMP14, impairing alveolarization. MMP14 promotes expansion of epithelial progenitor cells by unmasking cryptic EGF-like ectodomains that activate the EGF receptor (EGFR). Consistent with this, neutralization of MMP14 impairs EGFR-mediated alveolar regeneration, whereas administration of EGF or intravascular transplantation of MMP14(+) PCECs into pneumonectomized Vegfr2/Fgfr1-deficient mice restores alveologenesis and lung inspiratory volume and compliance function. VEGFR2 and FGFR1 activation in PCECs therefore increases MMP14-dependent bioavailability of EGFR ligands to initiate and sustain alveologenesis.     

Developmental signals do not further accentuate nonuniform postpneumonectomy compensatory lung growth.

Mechanical forces imposed on lung tissue constitute major stimuli for normal lung development and postpneumonectomy (PNX) compensatory growth and remodeling. Superimposing developmental signals on PNX signals augments compensatory alveolar growth but exaggerates airway-parenchymal dissociation (i.e., dysanaptic lung growth); the latter tends to offset benefits derived from the former. In adult dogs after PNX, lobar expansion and growth of the remaining lobes were markedly non-uniform (Ravikumar et al. J Appl Physiol 97:1567-1574, 2004). We hypothesized that superimposing developmental and post-PNX signals further accentuates nonuniformity of lobar growth. We used high-resolution computed tomography (HRCT) to follow regional lung expansion and growth in foxhounds undergoing right PNX at 2.5 mo of age compared with litter-matched control (Sham) animals; scans were performed 4 and 10 mo following surgery, i.e., before and after somatic maturity. Air and tissue volumes were measured in each lobe; tissue volume estimated by HRCT includes air-free tissue and blood in small vessels <1 mm. Interlobar nonuniformity of tissue volume was absent at 4 mo but evident 10 mo after PNX; growth of the remaining left lower lobe gradually lagged behind other lobes. At maturity, nonuniformity of lobar growth in pneumonectomized puppies was similar to that previously reported in pneumonectomized adults. We conclude that superimposing developmental and post-PNX signals enhances some aspects of compensatory lung growth and remodeling without altering its nonuniform spatial distribution.     

Upregulation of erythropoietin receptor during postnatal and postpneumonectomy lung growth

Circulating erythropoietin (EPO) stimulates erythrocytosis, whereas organ-specific local EPO receptor (EPOR) expression has been linked to angiogenesis, tissue growth, and development. On the basis of the observation of concurrent enhancement of lung growth and erythrocyte production during exposure to chronic hypoxia, we hypothesized that a paracrine EPO system is involved in mediating lung growth. We analyzed EPOR protein expression in normal dog lung tissue during postnatal maturation and during compensatory lung growth after right pneumonectomy (PNX). Membrane-bound EPOR was significantly more abundant in the immature lung compared with mature lung and in the remaining lung 3 wk after PNX compared with matched sham controls. COOH-terminal cytosolic EPOR peptides, which were even more abundant than membrane-bound EPOR, were also upregulated in immature lung but differentially processed after PNX. Apoptosis was enhanced during both types of lung growth in direct relationship to cellular proliferation and EPOR expression. We conclude that both developmental and compensatory lung growth involve paracrine EPO signaling with parallel upregulation but differential processing of EPOR.     

Cellular kinetics and modeling of bronchioalveolar stem cell response during lung regeneration

Organ regeneration in mammals is hypothesized to require a functional pool of stem or progenitor cells, but the role of these cells in lung regeneration is unknown. Whereas postnatal regeneration of alveolar tissue has been attributed to type II alveolar epithelial cells (AECII), we reasoned that bronchioalveolar stem cells (BASCs) have the potential to contribute substantially to this process. To test this hypothesis, unilateral pneumonectomy (PNX) was performed on adult female C57/BL6 mice to stimulate compensatory lung regrowth. The density of BASCs and AECII, and morphometric and physiological measurements, were recorded on days 1, 3, 7, 14, 28, and 45 after surgery. Vital capacity was restored by day 7 after PNX. BASC numbers increased by day 3, peaked to 220% of controls (P<0.05) by day 14, and then returned to baseline after active lung regrowth was complete, whereas AECII cell densities increased to 124% of baseline (N/S). Proliferation studies revealed significant BrdU uptake in BASCs and AECII within the first 7 days after PNX. Quantitative analysis using a systems biology model was used to evaluate the potential contribution of BASCs and AECII. The model demonstrated that BASC proliferation and differentiation contributes between 0 and 25% of compensatory alveolar epithelial (type I and II cell) regrowth, demonstrating that regeneration requires a substantial contribution from AECII. The observed cell kinetic profiles can be reconciled using a dual-compartment (BASC and AECII) proliferation model assuming a linear hierarchy of BASCs, AECII, and AECI cells to achieve lung regrowth.