黏蛋白对气道黏液高分泌的抑制及其机制研究

制造黏液是一种维持肺部健康的主要防御机制,然而黏液中主要糖蛋白成份即黏蛋白的过量产生却是哮喘、慢性阻塞性肺疾病(COPD)、囊性纤维化(CF)及肺癌的共同疾病特征.目前,以黏蛋白的过量表达与分泌作为靶标的治疗手段的研究刚刚起步.该文将讨论肺部黏蛋白基因表达及其表达产物释放到气道中的调控机制方面的最新研究进展,并提出抑制气道黏液高分泌的有效治疗策略.     

丁苯酞对哮喘小鼠气道黏液高分泌及IL-13、TNF-α的影响*

目的: 研究丁苯酞对哮喘小鼠气道黏液高分泌及白介素-13(IL-13)、肿瘤坏死因子-α(TNF-α)的影响。方法: 小鼠随机分为空白对照组、模型对照组、阳性对照组和丁苯酞高、中、低剂量(100、50、25 mg/kg)组(n=12)。实验第1日、8日、15日通过注射卵清白蛋白(OVA)致敏,第22日吸入OVA连续激发5周复制哮喘模型,同时在激发前给予丁苯酞20 mg/kg进行干预,观测哮喘行为学、气道杯状细胞及黏蛋白5ac(Muc5ac)的分泌,测定支气管肺泡灌洗液(BALF)粘度,采用ELISA法测定BALF中Muc5ac、IL-13及TNF-α的水平。结果: 与空白对照组比较,模型对照组小鼠打喷嚏、抓鼻及哮喘的程度显著加重(P＜0.01),小鼠气道上皮杯状细胞增生及Muc5ac的分泌显著增加(P＜0.01),BALF的粘度及其中的Muc5ac、IL-13和TNF-α的含量显著升高(P＜0.01);与模型对照组比较,25、50、100 mg/kg丁苯酞干预后哮喘行为学评分明显下降(P＜0.01);小鼠气道上皮杯状细胞增生、Muc5ac的分泌、BALF的粘度及其中的Muc5ac、IL-13和TNF-α的含量均明显降低(P＜0.05, 0.01)。结论: 丁苯酞具有抑制哮喘气道黏液高分泌而平喘的作用,缓解IL-13、TNF-α异常高表达是其抑制气道黏液高分泌的作用机制之一。     

当归对阴虚哮喘小鼠气道黏液高分泌及TNF-α/NF-κB信号通路的影响*

目的: 探讨当归对阴虚哮喘小鼠气道黏液高分泌及TNF-α/NF-κB信号通路的影响。方法: 取KM小鼠随机分为空白对照组、模型对照组、氨溴索组、当归低、中、高剂量(2、4、8 g/kg)组(n=12),采用卵蛋白与甲状腺片复制阴虚哮喘模型,观测当归对小鼠哮喘症状、IgE、TNF-α以及肺组织Muc5ac与NF-κB表达的影响。结果: 2、4、8 g/kg当归能明显缓解阴虚哮喘小鼠的哮喘症状,降低血清IgE与BALF中TNF-α水平,抑制肺组织Muc5ac与NF-κB的过度表达。结论: 当归具有明显的平喘作用,抑制TNF-α/NF-κB信号通路而缓解气道黏液高分泌是其平喘的作用机制之一。     

湿热环境习服和抗晕动病训练对晕动病的预防作用

目的：拟通过湿热环境习服性训练和抗晕动病训练两阶段,探究训练对降低晕动病发病率及等级的作用。方法：选取60名健康男性志愿者,配对分成实验组和对照组,实验组①一阶段采取模拟湿热环境静坐、快走、负重跑等训练,通过检测受试者主观感受、肛温、心率、血压、出汗率、汗盐浓度等指标确定受试者达到湿热环境习服;然后两组均在40℃、80％下进行Coriolis加速度转椅试验诱发晕动病,以Graybiel法评定晕动病得分及等级,以评价湿热环境习服训练是否可以降低晕动病发病率及等级;②三个月后实验组脱习服后进行二阶段常温下（20℃、50％）抗晕动病训练,共接受旋转转椅法训练10次,每次通过Graybiel法记录晕动病得分及等级;对照组不接受两阶段的训练。然后两组再次均进行Coriolis加速度转椅试验诱发晕动病,以Graybiel法评定晕动病得分及等级,用以评价抗晕动病训练是否可以降低湿热环境下晕动病发病率及等级。结果：①一阶段湿热环境习服训练后,实验组和对照组Graybiel评分及等级差异无显著性（P〉0．05）;②二阶段抗晕动病训练后,实验组Graybiel评分及等级较对照组有明显降低（P〈0．01）。结论：单纯湿热环境习服训练并不能帮助降低湿热环境下晕动病的发病率和等级;但抗晕动病训练可以有效降低发病率和等级。     

当归对实验性血虚便秘模型小鼠结肠组织形态和黏液分泌的影响

目的：观察当归对实验性血虚便秘模型小鼠的治疗作用及其对小鼠结肠组织形态和黏液分泌的影响。方法：60只KM小鼠,雌雄各半,随机分为6组（n=10）：正常对照组、血虚便秘组、阳性对照组、当归高、中、低剂量组。除正常对照组小鼠外,其余各组小鼠灌胃给予复方地芬诺酯（DNP）,皮下注射乙酰苯肼（APH）,腹腔内注射环磷酰胺（CPA）,复制血虚便秘小鼠模型。从实验的第14天起,当归组小鼠灌胃给予不同剂量的当归煎液（16.67,8.33,4.17 g/kg）,阳性对照组给予常通舒颗粒（5 g/kg）,血虚便秘模型组和正常对照组小鼠给予等体积生理盐水,每日1次,连续28 d。观察小鼠一般状态,检测首粒黑便排出时间（FBDT）、粪便和结肠含水量,取结肠组织进行HE和AB-PAS染色,观察小鼠结肠组织形态变化和黏液分泌情况。结果：与正常对照组比较,血虚便秘组小鼠出现血虚和便秘体征,FBDT显著延长、粪便和结肠含水量显著降低（P<0.01）,结肠黏膜和大肠腺萎缩、黏膜层变薄（P<0.01）,黏液分泌减少。与血虚便秘模型组比较,3个剂量的当归均能改善血虚便秘体征,显著缩短FBDT（P<0.05,P<0.01）,显著升高小鼠结肠含水量（P<0.05,P<0.01）;高、中剂量的当归能显著升高小鼠粪便含水量（P<0.05）;3个剂量当归均能改善血虚便秘模型小鼠的结肠黏膜和大肠腺萎缩,增加结肠黏液分泌,改善结肠润滑功能。结论：当归可改善结肠黏膜萎缩、增加结肠黏液分泌,从而软化粪便促进粪便排出。     

冷冻前后的低渗应激对小鼠孵化囊胚存活率的影响

本试验用10％或20％GL预处理5min,再移入GFS40中平衡0．5min二步法冷冻保存的小鼠孵化囊胚,解冻后24h内恢复率高达93％－97％,与对照组(99％)相比无显著差异(P＞0．05)。新鲜孵化囊胚在低渗液中平衡30min,0．25×PBS组恢复率达92％,而0．20×PBS组恢复率仅为50％,与对照组相比差异极显著(P＜0．01)。冷冻解冻后孵化囊胚直接进行低渗处理,结果0．50×PBS组的恢复率(72％)与对照组(88％)差异显著(P＜0．05),而0．30×、0．25×和0．20×PBS组的恢复率分别为58％、11％和0％。解冻后经培养的孵化囊胚对低渗处理的耐受力增强,0．50×PBS处理组的恢复率达94％,与对照组(98％)相比无显著差异(P＞0．05),0．30×、0．25×和0．20×PBS组的恢复率与对照组相比虽有极显著差异(P＜0．01),但与解冻后直接进行低渗处理组相比恢复率有较大提高(82％－26％)。     

低分子量肝素对慢性阻塞性肺疾病大鼠气道黏液分泌的影响

目的:观察低分子量肝素对慢性阻塞性肺疾病(COPD)大鼠血浆D-二聚体和气道黏液分泌的影响.方法:将30只Wistar大鼠随机分为正常对照组、COPD模型组、LMWH干预组,每组10只.采用熏吸香烟法加气管内注入脂多糖的方法建立COPD大鼠模型,LMWH干预组于COPD模型建立后皮下注射LMWH,检测各组大鼠血浆D-二聚体水平及气道黏液细胞数的变化.结果:COPD模型组血浆D-二聚体水平及气道黏液细胞数较正常对照组均明显升高(P＜0.05),而低分子量肝素治疗组二者较COPD模型组均明显下降(P＜0.05).血浆D-二聚体水平与气道黏液细胞数呈显著正相关(r=0.946,P=0.04).结论:低分子量肝素在改善凝血功能的同时可以减少COPD气道黏液分泌,有助于疾病的控制和转归.     

色氨酸对应激小鼠行为学和脑内单胺类递质的影响

本文以小鼠为实验材料建模,依次进行了Morris水迷宫、跳台、强迫游泳实验。结果显示,应激可导致小鼠学习记忆能力下降,容易出现绝望情绪,下丘脑5-HT含量下降,NE含量上升,灌胃高低剂量色氨酸(100,200mg·kg-1 bw)均可显著提高小鼠学习记忆能力,缓和绝望情绪。低剂量色氨酸在增加下丘脑5-羟色胺(5-HT)含量和降低去甲肾上腺素(NE)含量方面效果更显著。结果表明,适量色氨酸可以有效改善应激小鼠相关行为学评分,其机制可能与下丘脑5-HT和NE的含量有关。     

半夏泻心汤对束缚应激小鼠免疫功能的影响

目的研究半夏泻心汤对束缚应激小鼠免疫功能的影响.方法小鼠随机分为对照组、束缚模型组、低浓度半夏泻心汤组、中浓度半夏泻心汤组和高浓度半夏泻心汤组5组,束缚7 d后测定各组巨噬细胞的吞噬指数、外周血T淋巴细胞数量和抗体生成细胞IgM的分泌量.结果束缚模型组各指标均显著低于对照组(P<0.05);半夏泻心汤各浓度组均可显著升...     

Metabolic and hormonal acclimation to heat stress in domesticated ruminants

Environmentally induced periods of heat stress decrease productivity with devastating economic consequences to global animal agriculture. Heat stress can be defined as a physiological condition when the core body temperature of a given species exceeds its range specified for normal activity, which results from a total heat load (internal production and environment) exceeding the capacity for heat dissipation and this prompts physiological and behavioral responses to reduce the strain. The ability of ruminants to regulate body temperature is species- and breed-dependent. Dairy breeds are typically more sensitive to heat stress than meat breeds, and higher-producing animals are more susceptible to heat stress because they generate more metabolic heat. During heat stress, ruminants, like other homeothermic animals, increase avenues of heat loss and reduce heat production in an attempt to maintain euthermia. The immediate responses to heat load are increased respiration rates, decreased feed intake and increased water intake. Acclimatization is a process by which animals adapt to environmental conditions and engage behavioral, hormonal and metabolic changes that are characteristics of either acclimatory homeostasis or homeorhetic mechanisms used by the animals to survive in a new 'physiological state'. For example, alterations in the hormonal profile are mainly characterized by a decline and increase in anabolic and catabolic hormones, respectively. The response to heat load and the heat-induced change in homeorhetic modifiers alters post-absorptive energy, lipid and protein metabolism, impairs liver function, causes oxidative stress, jeopardizes the immune response and decreases reproductive performance. These physiological modifications alter nutrient partitioning and may prevent heat-stressed lactating cows from recruiting glucose-sparing mechanisms (despite the reduced nutrient intake). This might explain, in large part, why decreased feed intake only accounts for a minor portion of the reduced milk yield from environmentally induced hyperthermic cows. How these metabolic changes are initiated and regulated is not known. It also remains unclear how these changes differ between short-term v. long-term heat acclimation to impact animal productivity and well-being. A better understanding of the adaptations enlisted by ruminants during heat stress is necessary to enhance the likelihood of developing strategies to simultaneously improve heat tolerance and increase productivity.     

Beneficial developmental acclimation in reproductive performance under cold but not heat stress

Thermal plasticity can help organisms coping with climate change. In this study, we analyse how laboratory populations of the ectotherm species Drosophila subobscura, originally from two distinct latitudes and evolving for several generations in a stable thermal environment (18 °C), respond plastically to new thermal challenges. We measured adult performance (fecundity traits as a fitness proxy) of the experimental populations when exposed to five thermal regimes, three with the same temperature during development and adulthood (15-15 °C, 18-18 °C, 25-25 °C), and two where flies developed at 18 °C and were exposed, during adulthood, to either 15 °C or 25 °C. Here, we test whether (1) flies undergo stress at the two more extreme temperatures; (2) development at a given temperature enhances adult performance at such temperature (i.e. acclimation), and (3) populations with different biogeographical history show plasticity differences. Our findings show (1) an optimal performance at 18 °C only if flies were subjected to the same temperature as juveniles and adults; (2) the occurrence of developmental acclimation at lower temperatures; (3) detrimental effects of higher developmental temperature on adult performance; and (4) a minor impact of historical background on thermal response. Our study indicates that thermal plasticity during development may have a limited role in helping adults cope with warmer - though not colder - temperatures, with a potential negative impact on population persistence under climate change. It also emphasizes the importance of analysing the impact of temperature on all stages of the life cycle to better characterize the thermal limits.     

小儿支原体肺炎合并气道黏液栓形成的气道微生物菌群变化

研究支原体肺炎（MPP）合并气道黏液栓的患儿气道微生物菌群的变化。

选取2018年1月至2020年1月在我院诊治的116例MPP患儿为研究对象。根据支气管镜检查结果,将56例合并气道黏液栓的MMP患儿纳入MPP合并黏液栓组,60例无气道黏液栓的MPP患儿纳入单纯MPP组。用16S rRNA测序技术分析各组患儿支气管灌洗液中气道菌群的组成,比较各组气道微生物菌群分布差异,采用Pearson相关性分析探讨MPP合并黏液栓组菌属与临床参数的相关性。

单纯MPP组和MPP合并黏液栓组的优势菌门是软壁菌门、拟杆菌门、厚壁菌门。MPP合并黏液栓组软壁菌门和变形菌门相对丰度显著高于单纯MPP组（P = 0.012、0.001）,两组的拟杆菌门、厚壁菌门、放线菌门和梭杆菌门相对丰度间差异无统计学意义（P＞0.05）。单纯MPP组和MPP合并黏液栓组的优势菌属包括支原体属、放线菌属、鞘氨醇单胞菌属、苯杆菌属、伊丽莎白菌属、普氏菌属、链球菌属和韦荣球菌属。相比于单纯MPP组,MPP 组合并黏液栓组支原体属、放线菌属的相对丰度较高（P＜0.001）,鞘氨醇单胞菌属和伊丽莎白菌属相对丰度较低（P＜0.001）。单纯MPP组和MPP合并黏液栓组的苯杆菌属、普氏菌属、链球菌属和韦荣球菌属的相对丰度差异无统计学意义（P＞0.05）。相比于单纯MPP组,MPP合并黏液栓组菌群多样性及相对丰度差异不具有统计学意义（P＞0.05）。MPP合并黏液栓组链球菌属的相对丰度与患儿年龄呈显著负相关（r = −0.524,P = 0.014）,和发热时间呈显著正相关性（r = 0.684,P = 0.002）。

MPP合并气道黏液栓患儿气道菌群的变化可能是气道黏液栓形成的重要因素,MPP合并气道黏液栓患儿链球菌属的相对丰度与患儿年龄呈负相关,与发热时间呈正相关,值得临床深入研究。

     

Salt stress and fluctuating light have separate effects on photosynthetic acclimation,but interactively affect biomass

In nature, soil salinity and fluctuating light (FL) often occur concomitantly. However, it is unknown whether salt stress interacts with FL on leaf photosynthesis, architecture, biochemistry, pigmentation, mineral concentrations, as well as whole-plant biomass. To elucidate this, tomato (Solanum lycopersicum) seedlings were grown under constant light (C, 200 μmol m⁻² s⁻¹) or FL (5–650 μmol m⁻² s⁻¹), in combination with no (0 mM NaCl) or moderate (80 mM NaCl) salinity, for 14 days, at identical photoperiods and daily light integrals. FL and salt stress had separate effects on leaf anatomy, biochemistry and photosynthetic capacity: FL reduced leaf thickness as well as nitrogen, chlorophyll and carotenoid contents per unit leaf area, but rarely affected steady-state and dynamic photosynthetic properties along with abundance of key proteins in the electron transport chain. Salt stress, meanwhile, mainly disorganized chloroplast grana stacking, reduced stomatal density, size and aperture as well as photosynthetic capacity. Plant biomass was affected interactively by light regime and salt stress: FL reduced biomass in salt stressed plants by 17%, but it did not affect biomass of non-stressed plants. Our results stress the importance of considering FL when inferring effects of salt-stress on photosynthesis and productivity under fluctuating light intensities.     

Exploring epidermal mucus protease activity as an indicator of stress in Atlantic sturgeon (Acipenser oxyrinchus oxyrhinchus)

Atlantic sturgeon are anadromous fish that spend much of their life in near-shore environments. They are designated as “threatened” by the Committee on the Status of Endangered Wildlife in Canada and listed by the IUCN as “near threatened.” In Canada, Atlantic sturgeon support small commercial fisheries in the Saint John River, New Brunswick, and the St. Lawrence River, Quebec. While occupying the marine environment, the species is susceptible to various anthropogenic stressors, including by-catch in trawl fisheries and through interactions with coastal engineering projects such as tidal power development. Atlantic sturgeon are also susceptible to implantation of acoustic tags used by researchers to study their movement ecology. These stressors can cause physiological and behavioural changes in the fish that can negatively impact their viability. Because the species are commercially important, and are also of conservation concern, it is important to understand stress responses of Atlantic sturgeon to better mitigate the effects of increased industrial activity in the coastal zone. This study used proteomics to identify and characterize protease activity and identify putative novel protein biomarkers in the epidermal mucus of Atlantic sturgeon. Changes in protein profiles in Atlantic sturgeon epidermal mucus as a result of by-catch and surgery stress were investigated using one-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis and mass spectrometry. Proteolytic activity was identified and characterized using inhibition zymography, which provided information on the classes of proteases that are associated with stress. Samples were collected from Atlantic sturgeon on the Minas Basin, Nova Scotia, Canada, after capture by brush weir and otter trawl, and after surgical implantation of a V16-69 kHz VEMCO acoustic tag. Significant proteins found in the epidermal mucus include various inflammatory proteins, with calmodulin and complement 9 found ubiquitously, and more rarely lysosome C, identified in a brush weir capture sample. Serum albumin, a blood plasma protein, was another ubiquitous protein and verifies how the sample collection method provides a picture of the internal systems. Protease activity was dominantly exhibited by matrix metalloproteases and serine proteases in all sample collections, with serine proteases more active in otter trawl captures than in brush weir captures. By identifying potential protein biomarkers of stress, this study is an example of a non-invasive method for measuring stress in Atlantic sturgeon. Understanding the defence mechanism and release of non-specific biomarkers can be used to improve conservation regulations, as well as to contribute to the limited scientific knowledge on the stress response of Atlantic sturgeon.     

Functional leaf traits,plant communities and acclimation processes in relation to oxidative stress in trees: a critical overview

Tropospheric ozone exercises pressure on vegetation in combination with other oxidative factors such as strong sunlight, UV‐B radiation, high temperatures and water shortage. The relationship established between these factors and the plants can be either antagonistic (cross‐resistance) or synergistic. Response mechanisms are activated involving physiological, chemical and morphological features. Overall sensitivity (or resistance) is determined by the amount of total oxidative pressure in relation to the plant's physiological plasticity [i.e. its ability (within its own resilience potential) to alter its structure and functions in order to react to the oxidative pressure]. Within different populations of the same species, functional leaf traits (leaf area and thickness, leaf mass per area or specific leaf area, tissue thickness) may vary in relation to the extent that the plant succeeds in acclimating to ambient oxidative pressure. The behaviour of a tree in an oxidative environment can be interpreted by means of leaf structure analysis. Leaves presenting high tissue density (and thus low intercellular space content) display a high degree of acclimation to stressors, react little to environmental changes and are characterized by remarkable longevity. Leaves of this type also have a high photosynthesis capacity per surface unit (due to the N content per surface unit) and a high P_N/G_W (or water use efficiency, WUE). Thus, they are able to support detoxification processes. These morphological traits are to be found in adult plants in late successional stands and, above all, in ambients that have already been subjected to oxidative pressure. However, in early successional species and during the dynamic stages of growth (e.g. in the renewal occurring along forest edges), it is the opposite leaf traits that prevail: low leaf density, high photosynthesis capacity per dry weight unit, low WUE, low leaf longevity. These traits make plants far more reactive to environmental changes (e.g. they exploit the light from sun flecks much more effectively), but enable them to achieve only a low degree of acclimation and a poor ability to support detoxification processes. Whereas adult forests display a high level of ecological resilience and have a relatively good tolerance of ozone, the renewal stages are (at least potentially) more vulnerable. In these environments, ozone can alter the competition among genotypes and favour more resistant ones. Among the sectors most at risk, we must include communities growing at the edge of their ecological range, for whom even a slight increase in oxidative pressure can trigger substantial degenerative processes.     

Interactive effects of acclimation temperature and short‐term stress exposure on resistance traits in the butterfly Bicyclus anynana

The ability to buffer detrimental effects of environmental stress on fitness is of great ecological importance because, in nature, pronounced environmental variation may regularly induce stress. Furthermore, several stressors may interact in a synergistic manner. In the present study, plastic responses in cold, heat and starvation resistance are investigated in the tropical butterfly Bicyclus anynana Butler, 1879, using a full factorial design with two acclimation temperatures (20 and 27 °C) and four short‐term stress treatments (control, cold, heat, starvation). Warm‐acclimated butterflies are more heat‐ but less cold‐tolerant as expected. Short‐term cold and starvation exposure reduce cold and heat resistance, and short‐term heat exposure decreases cold but increases heat resistance. Starvation resistance is not affected by any of the short‐term treatments. Thus, the effects of short‐term stress exposure are either neutral or negative, except for a positive effect of heat exposure on heat resistance, indicating the negative effects of pre‐exposure to stress. Interestingly, significant interactions between acclimation temperature and short‐term stress exposure for heat and cold resistance are found, demonstrating that larger temperature differences incur more damage. Therefore, animals may not generally be able to benefit from pre‐exposure to stress (through ‘hardening’), depending on their previously experienced conditions. The complex interactions between environmental variation, stress and resistance are highlighted, warranting further investigations.     

Autophagy is essential for ultrafine particle-induced inflammation and mucus hyperproduction in airway epithelium

Environmental ultrafine particulate matter (PM) is capable of inducing airway injury, while the detailed molecular mechanisms remain largely unclear. Here, we demonstrate pivotal roles of autophagy in regulation of inflammation and mucus hyperproduction induced by PM containing environmentally persistent free radicals in human bronchial epithelial (HBE) cells and in mouse airways. PM was endocytosed by HBE cells and simultaneously triggered autophagosomes, which then engulfed the invading particles to form amphisomes and subsequent autolysosomes. Genetic blockage of autophagy markedly reduced PM-induced expression of inflammatory cytokines, e.g. IL8 and IL6, and MUC5AC in HBE cells. Mice with impaired autophagy due to knockdown of autophagy-related gene Becn1 or Lc3b displayed significantly reduced airway inflammation and mucus hyperproduction in response to PM exposure in vivo. Interference of the autophagic flux by lysosomal inhibition resulted in accumulated autophagosomes/amphisomes, and intriguingly, this process significantly aggravated the IL8 production through NFKB1, and markedly attenuated MUC5AC expression via activator protein 1. These data indicate that autophagy is required for PM-induced airway epithelial injury, and that inhibition of autophagy exerts therapeutic benefits for PM-induced airway inflammation and mucus hyperproduction, although they are differentially orchestrated by the autophagic flux.     

Effect of temperature level on thermal acclimation in Large White growing pigs

The effect of temperature level (24°C, 28°C, 32°C or 36°C) on performance and thermoregulatory response in growing pigs during acclimation to high ambient temperature was studied on a total of 96 Large White barrows. Pigs were exposed to 24°C for 10 days (days -10 to -1, P0) and thereafter to a constant temperature of 24°C, 28°C, 32°C or 36°C for 20 days. Pigs were housed in individual metal slatted pens, allowing a separate collection of faeces and urine and given ad libitum access to feed. Rectal (RT) and cutaneous (CT) temperatures and respiration rate (RR) were measured three times daily (0700, 1200 and 1800 h) every 2 to 3 days during the experiment. From day 1 to 20, the effect of temperature on average daily feed intake (ADFI) and BW gain (average daily gain, ADG) was curvilinear. The decrease of ADFI averaged 90 g/day per °C between 24°C and 32°C and 128 g/day per °C between 32°C and 36°C. The corresponding values for ADG were 50 and 72 g/day per °C, respectively. The 20 days exposure to the experimental temperature was divided in two sub-periods (P1 and P2, from day 1 to 10 and from day 11 to 20, respectively). ADFI was not affected by duration of high-temperature exposure (i.e. P2 v. P1). The ADG was not influenced by the duration of exposure at 24°C and 28°C groups. However, ADG was higher at P2 than at P1 and this effect was temperature dependent (+130 and +458 g/day at 32°C and 36°C, respectively). In P2 at 36°C, dry matter digestibility significantly increased (+2.1%, P < 0.01); however, there was no effect of either duration or temperature on the digestibility of dry matter at group 24°C and 32°C. RT, CT and RR were measured three times daily (0700, 1200 and 1800 h) every 2 to 3 days during the experiment. Between 28°C and 36°C, RT and CT were lower during P2 than during P1 (-0.20°C and -0.23°C; P < 0.05), whereas RR response was not affected by the duration of exposure whatever the temperature level. In conclusion, this study suggests that the effect of elevated temperatures on performance and thermoregulatory responses is dependent on the magnitude and the duration of heat stress.