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mTOR signaling pathway is a highly conserved intracellular signaling pathway,which partici-pates in several signaling pathways, such as PI3K/AKT/mTOR, AKT/TSC1-TSC2/Rheb/mTOR, LKB1-AMPK-TSC-mTOR and FGF-10-Spry2-mTORC1-STAT3/HIF-1α-VEGF-A. mTOR signaling implicate in the regulation of the development of lung and many pulmonary diseases in many aspects,may be connected to bron-chopulmonary dysplasia. Bronchopulmonary dysplasia is one of the very common chronic lung diseases in pre-term,physical and chemical factors have been shown to induce acute lung injury, aberrant wound healing and lung fibrosis in the immature lung. This review summarizes relationship of mTOR signaling among lung develop-ment,acute lung injury and lung fibrosis,to explore the role of mTOR signaling in the development of bronchop-ulmonary dysplasia,in hope of providing novel method in the prevention and treatment of bronchopulmonary dysplasia.
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Aim To study the development of acute lung inflammation in mice induced by activation of the complement alternative pathway and the changes of the related indicators, and to provide an ideal pathological model of acute lung inflammation in mice for drug screening and intervention. Methods Cobra venom factor( CVF) was used to activate complement alterna-tive pathway of SPF Kunming mice by intravenous injection. According to different sampling time, the mice were divided into 15 min, 30 min, 1 h, 2 h, 6 h group, and the parallel PBS control groups were set at the same time. Lung coefficient, lung water content, myeloperoxidase ( MPO ) activity, BALF cell number and protein content were tested. The pathological changes of lung tissue were observed by HE staining. The concentration of IL-6 , TNF-α, P-selectin and ICAM-1 in bronchoalveolar lavage fluid ( BALF ) and serum were determined by ELISA. Results CVF caused pulmonary inflammatory cell infiltration in mice obviously. Compared with PBS groups, MPO activity of lung tissue, BALF cell and the protein concentration were significantly increased. The contents of IL-6, TNF-α, P-selectin in BALF and serum were in-creased, and the content of ICAM-1 in serum was also increased. The content of P-selectin in BALF reached the first peak at 30 min point, the content of IL-6 and TNF-α in BALF reached the first peak at 1 h point, but the indicators had no further changes at 2 h point, and all the indicators rose again at 6 h point. The lev-els of IL-6 and TNF-α in serum reached peak at 1 h point,then the content showed lower levels at the sub-sequent time points. The levels of P-selectin and ICAM-1 in serum increased along the time. Lung coef-ficient, lung water content and ICAM-1 of the BALF showed no significant alteration. Conclusion The ac-tivation of the complement alternative pathway can lead to acute lung inflammation in mice and the inflammato-ry response is the most obvious at 30 min to 1 h. The study could provide an ideal pathological model of a-cute lung inflammation in mice for drug screening and intervention.
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Objective To observe the effect of Valsartan on a rat model of acute lung injury and the expression of transforming growth factor-β,TGF-β) ,Smad2/3, Smad7. Methods Twenty-four male adult Sprague-Dawley rats were random divided into three groups : The bleomycin (BLM) group, the control group, and the Valsartan group. Each group contained eight rats. The Valsartan group was treated with Valsartan everyday at a dose of 20 mg/kg after a single intratracheal instillation of bleomycin at a dose of 5mg/kg. BLM group was treated with saline instead of Valsartan after an instillation of bleomycin. The control group was treated with saline instead of Valsartan and bleomycin. Each group was killed at the 7th day after instillation. The lung tissues were harvested for H. E. stain, the immunohistochemistry was used to detect the expressions of TGF-β1, Smad2/3 ,and Smad7. Results The degree of alveolitis in the Valsartan group was ameliorated, compared with those in BLM group (P ＜0. 01). The expressions of TGF-β1 and Smad2/3 in lung tissue of the Valsartan group were significantly lower than that of BLM group(P ＜0. 01). The expressions of Smad7 in lung tissue of the Valsartan group were significantly higher than that of BLM group (0.23 ±0. 02 vs0. 36 ±0.03, P ＜0.01). Conclusions Valsartan could alleviate acute lung injury in rats, which probably be due to the expression decrease of TGF-β1 and Smad2/3 and the expression increase of Smad7 in lung tissues.
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Objective To research the effect of octreotide on the lung injury of far place organ after ischemia-reperfusion in rabbit liver.Methods Prings maneuver rabbit hepatic ischemia-reperfusion models were established. 24 adult New Zealand rabbits were random divided into three groups: group Ⅰ (sham operative group) , group Ⅱ (ischemia-reperfusion by physiological saline group) and group Ⅲ (octreotide preconditioning group). To group Ⅲ, we injected octreotide of 20μg/kg to abdominal cavity and octreotide of 30(μg/kg to skin following, and octreotide was dissolved into 2ml with 0. 9% physiological saline. To group Ⅰ and Ⅱ, octreotide were replaced with the same amount of physiological saline. The changes of MAP, HR in every group were recorded at the time before ischemia (T1 ) , 30min (T2) after ischemia, 30min(T3) , 60min(T4) , 120min(T5) , 240min(T6) after reperfusion. The tumor necrosis factor-alpha (TNF-a) and interleukin-lbeta (IL-1β) in the plasma in every group at T1, T2, T3, T4 , T5, T6 were detected. These rabbits were killed 240 min after reperfusion, then the lung's hepatocellular ultrastructures of every group were observed under electromicroscope, and the apoptosis of lung was detected by TUNEL. Results The MAP, HR of group Ⅱ and group Ⅲ were lower than that of group Ⅰ at T2 to T4. Moreover, group Ⅱ were lower than that of group Ⅲ (P <0.05). The TNF-a, IL-1β of group Ⅱ (fromT2) and group Ⅲ ( from T3) were higher than that of group Ⅰ ( P < 0.05) , and group Ⅲ were lower than group Ⅱ after ischemia (P <0. 01). Through electromicroscope, we found that the injury of the lungs hepatocellular ultrastructure in group Ⅲ was slighter than that in group Ⅱ . We detected the apoptosis of the lung organizes by TUNEL under 5 fields of light microscopes, and found that the apoptosis counts of group Ⅱ (55. 82 ±4. 19) and group Ⅲ (32. 17 ±3. 10) were more than that of group Ⅰ (3. 96 ±0. 87), and group Ⅲ were less than thatof group Ⅱ (P < 0. 01). Conclusion Octreotide can protect the lung injury of far place organ after ische-mia-reperfusion in rabbit liver.
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Eosinophilia accompanied by eosinophilic invasion and organ dysfunction may develope idiopathic hypereosinophilic syndrome. Any organ can be involved including bone marrow, lung, skin, heart, gastrointestinal tract and nervous system. Cough, dyspnea, pleural effusion or chest pain are common pulmonary manifestation, and they may be attributed to parenchymal infiltration, pulmonary embolism or heart failure. We report a 43-year-old woman with idiopathic hypereosinophilic syndrome involving bone marrow, skin, and lung. The patient developed acute dyspnea and chest pain. High resolution CT demonstrated multiple wedge-shaped segmental involvement with pleural effusion thought to be a pulmonary infarction or heart failure. Echocardiography could not find any abnormality. Lung biopsy showed interstitial eosinophilic infiltration with increased eosinophils in BAL fluid. She was treated with high dose corticosteroid and hydroxyurea. Within few days, most of her symptoms disappeared and chest radiography nearly cleared up.
Subject(s)
Adult , Female , Humans , Biopsy , Bone Marrow , Chest Pain , Cough , Dyspnea , Echocardiography , Eosinophilia , Eosinophils , Gastrointestinal Tract , Heart , Heart Failure , Hydroxyurea , Hypereosinophilic Syndrome , Lung , Nervous System , Pleural Effusion , Pulmonary Embolism , Pulmonary Infarction , Radiography , Skin , ThoraxABSTRACT
The preventive effects of some drugs on pulmonary lipid peroxi-dation and inborn oxidation protectant system in the lungs were observed in rats after the animals were exposed to 200 ppm of hydrogen sulfide (H2S) for 3 hours.Malondialdehyde (MDA) level of the lungs and bronchoalveolar lavage fluid (BALF),superoxide dismutase (SOD) activity,glutathione(GSH) and vitamin E (VE) levels of the lungs were determined in the 6th and 12th hour after H2S inhalation.It was found that a significant increase of MDA level of both the lungs and BALF and a significant decrease of SOD activity and GSH and VE level occured after a single exposure to 200 ppm of H2S inhalation.On the contrany,the MAD level of every group of which the animals had been medicated for prevention was lower than that of the intoxicated groups.Among the premedicated groups,the MDA level of 4-dimethylaminophenol(DMAP) group,VE group,and NaNO2 group was not different from that of the normal except that the MDA level in BALF was higher in VE and NaNO2 group than in the control.In every premedicated groups,SOD activity was increased and GSH and VE levels were elevated.These facts suggest that DMAP,NaNO2,VE,dexamethasone and anisoda-mine all could reduce the MDA level and elevate the capacity of the oxidation protectant system of the lungs after H2S inhalation.It is concluded that there are drugs to protect victims from H2O intoxication while DMAP,NaNO2 and VE are relatively more potent among the drugs used in this study.
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Acute lung injury(ALI)/acute respiratory distress syndrome(ARDS),the complicated and devastating illness,resulted from various processes of systemic inflammatory response syndrome(SIRS),injure directly or indirectly the lung.With the advance of investigations in SIRS and multiple organs disfunction syndrome(MODS),inflammation development and control have been considered to be the important mechanism of ALI/ARDS.The research hotspot is also focused on the inflammatory cells and cytokines.Dachengqi decoction can influence on the functions of inflammatory cells and cytokines,so the strategies of anti-inflammatory treatment on immunoregulation became the key point for prevention and treatment of ALI/ARDS with traditional Chinese medicine.
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The roles of leukocytes and prostaglandins in mediating alterations of pulmonary hemodynainics and lung fluid exchange after intravenous autologous zymo-san-activated plasma (ZAP) challenge is investigated in 14 conscious goats with chronic lung-lymph-fistula. In the control group, ZAP infusion causes the mean pulmonary arterial pressure (Ppa) markedly elevate, lung lymph flow (QI) and the lymph-to-plasma protein concentration ratio (L/P) increase. There is a significant correlation between Ppa and the content of plasma TXB2. In antiPMNs serum-induced leukopenia group, the extent of increment in Pp a is not as obvious as the normal goats, and no marked change is observed in QI, L/P and content of TXB2. These results indicate: l.TXA2 releases from leukocytes may affect lung fluid exchange during ZAP infusion; 2. leukocytes may play an important role in ZAP-induced lung injury.
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The experimental blast lung injuries are as follows: 1.permiability of the alveolar epithclium(AE),capillary endothelium(CE) and their intercellular junctions increased; 2.small vacuoles,large vacuoles formation and cell membrane damage in the AE and CE increased in amounts; 3.blood platelets aggregated and neutrophils trapped in the capillary lumen.These changes are more serious in the CE and especially 72 h after trinitrotoluene(TNT)explosions.These suggest that the CE is more sensitive to blast injury than AE,and the CE damage may be related to the neutrophils trapping and platelets aggregation in the capillary lumens.
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The separation,purification and activity determination of basic fibroblast growth factor (bFGF) with nucleic acid molecular hybridization was described and the changes of bFGF in lung injury treated with prostacy-clin were observed.It was found that bioactive bFGF and bFGF-mRNA could only be found in the injured lung tissues but not in the normal lungs.Administration of prostacyclin could slightly elevate the activity of bFGF and signficantly increase the level of bFGF-mRNA.The findings of this study suggest that there is an increase of bFGF level after lung injury,prostacyclin can influence the expression of bFGF,and bFGF plays an important role in the repair of the injured lung tissues.
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The role of free radicals in the precipitation of lung damage after hydrogen sulfide inhalation was investigated in rats, which were killed right after and in the 1st, 6th,12th, 24th, and 72nd hour after exposure to 100 and 220 ppm of hydrogen sulfide (H2S) for 3 hours respectively. Malondialdehyde(MDA) level in lung homogenate and in bronchoalveolar lavage fluid (BALF), protein content and the number of leucocytes and pulmonary alveolar macrophages (PAM) in BALF, superoxide dismutase(SOD),glutathione(GSH),and vitamin E(VE)level in lung tissue and blood were determined. It was found that H2S inhalation resulted in an increase of MDA level which occurred much earlier after exposure to 220 ppm than after exposure to 100 ppm. Protein content was increased in the 1st, 6th, and 12th hour after inhalation. The number of leucocytes and PAM were increased, which implies the existence of inflammatory response in the respiratory tract. SOD activity decreased in the early period after inhalation but significantly increased later. Both GSH and VE levels decreasedThese findings suggest that H2S inhalation induces an inflammatory response in the respiratory tract and an increase of free radical formation which in turn brings about exessive lipid peroxidation. It is concluded that free radical formation is a contributing factor of lung damages after H2S inhalation.
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Forty-one burn patients were divided into inhalation injury and non-inhalation injury groups.It was found that in the inhalation injury group,TXB2 level and TXB2/G-keto-PGF1? ratio in plasma and lung tissue were significantly elevated,circulatory platelet aggregate ratio markedly decreased,and blood viscosity greatly increased.Histopathologically,congestion,edema,hemorrhage and thrombosis were seen in lung tissue.The changes of TXB2 level and TXB2/6-keto-PGF1?ratio were parallel to the clinical course of the development of respiratory failure in the patients with body surface burns complicated with inhalation injury.It is believed that the imbalance of TXA2/PGI2 is one of the factors of respiratory failure in severe body surface burns complicated with inhalation injury.
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The canine model to study inhalaton injury established in our lab was employed,and neutrophil NADPH oxidase activity,blood gas analysis,lung water volume,chest radiographs,and pulmonary histopathological changes were observed in the dogs after they were exposed to smoke inhalaton.It was found that carbon monoxide poisoning,hypoxemia,metabolic aci-dosisi respiratory alkalosis and lung damage developed rapidly and early after smoke inhalation;white blood cells disappeared from the circulation 5 minutes after injury onward;the activity of neutrophil NADPH oxidase increased gradually from the 30th minute to the 6th hour after injury,then decreased and approached to its preinjury level in the 12th hour after injury.It is postulated on the basis of the above findings that neutrophils would accumulate in the lungs after smoke inhalation and experince a "respiratory burst" characterized by the activation of NADPH oxidase and the production of large amounts of oxygen and other active oxygen radicals,which would play a significant role in the pathogenesis of acute lung damage in the early stage of smoke inhalation injury.
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Sixty-six rabbits were divided into 2 groups, the control group and the experimental group. The latter was subdivided into 10 groups according to the time of observation after burn injury including 2nd-hour group to 30th-day group. Each group consisted of 6 animals. Specimens from the trachea and the lungs were examined with optical microscopy, scanning electron microscopy and transmission electron microscopy.No obvious lesion was seen in the specimens from the control. In the experimental group, various pathological changes began to appear from the 6th hour after injury. In the trachea and bronchi, congestion of varying degrees, edema, leucocytic infiltration, lodging, adhesion, breaking or separation of cilia, and increase of goblet cells and Clara cells in number weie found. In. the lungs, interstitial edema of varying degrees, accumulation and infiltration of neutro-phils in capillaries, pulmonary interstitium and alveolar spaces, decrease in num ber of type II pneumocytes and their lamellar bodies, vacuolization of lamellar bodies, and phagocytosis of lamellar bodies by macrophages were seen. Most prominent changes were shown on the 3rd day postburn, and they began to alleviate on the 7th day. The number of type II pneumocytes and their lamellar bodies gradually increased number. Some lesions still existed on the 30th day postburn but no significant fibrosis could be found. The occurrence and development of the main lesions and their significance were discussed.
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Histopathological and ultrastructural changes of the lungs were observed in various intervals after high-velocity bullet wounds of the two thighs of dogs. It was found that histologically there were microvascular dilatation, congestion, capillary rupture, interstitial and alveolar bleeding, focal atelecta-sis and pulmonary emphysema in the first half hour and the 6th hour after injury. In addition, microvascular embolism and hyaline membrane formation were seen in the 24th and 72nd hour after injury. Under electron microscopy, there were swelling of capillary endothelium, swelling, degeneration and necrosis of type I pneumocytes, shortening and decreasing of the microvilli of type II pneu-mocytes, significant vacuolation of the lamonar bodies, accumulation of leucocytes and platelets in the capillary lumen,and obvious decrease of the granules in the leucocytes. The mechanism of the pulmonary injury accompanying bullet wound of the thighs was discussed.
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The pulmonary toxicology after H2S inhalation was studied with bronchoaleveolar lavage (BAL),ultracentrifuge.and optical and electron microscopy in rats.The changes of the activities of lactate dehydrogenase,alkaline phosphatase,acid phosphatase and angiotension converting enzyme in BAL fluid were used as indicators of cellular damages.those of leucocytic count as the indicator of inflammatory response,and those of the concentration of protein and Evans blue as the indicator of the alterations of vascular permeability.In addition,the effects of H2S on lipid peroxidation,natural antioxidative system and energy substances and the changes of phospholipid concentration in BAL fluid were also studied.The results were as follows:(1)Inhalation of H2S exerted a severe cytotoxic effect on the lung tissues resulting in damages on various types of cells and a severe edematogenic effect on lung parenchyma.(2)The development of pulmonary edema in H2S intoxication resulted from a combination of different pathogenic factors.(3)The biochemical changes and their recovery occurred earlier than those of the pathological changes.The effecacy of 6 categories of drugs including 25 medicaments against H2S intoxication was e-valuated in mice,and 10 drugs were found prophylactically effective.The effects of various methe-moglobin-forming substances and some other drugs were also investingated in their treatment for H2S intoxication in rabbitsand dogs.It was concluded that methemoglobin-forming substances could be used as specific antidotes but could not prevent or diminish the lung damages due to H2S inhalation unless they were administered in association with dexamethasone,vitamin E,and anisodamine.Eventually,a postulated scheme of the medical treatment for H2S intoxication was presented.