Long-term Changes in Mouse Lung Following Inhalation of a Fibrosis-inducing Dose of 239PuO2: Changes in Collagen Synthesis and Degradation Rates

Summary

Mice were exposed by nose-only inhalation to ²³⁹PuO₂, which resulted in an IAD of 1110 ± 29 Bq. At various times after exposure, rates of collagen metabolism were measured using validated in vivo methods based on the administration of radiolabelled proline, together with a large flooding dose of unlabelled proline and measurement of its incorporation into lung collagen as hydroxyproline. Dramatic increases in both synthesis and degradation rates of collagen were observed. At 54 days after exposure the fractional synthesis rates in experimental mice were almost five times those in controls (control: 3·2 ± 0·6%/day, ²³⁹PuO₂-exposed: 14·5 ± 0·4%/day) and by 300 days synthesis rates, although declining, were still more than double the control values. A similar pattern of change was observed for collagen degradation. The combination of changes in synthesis and degradation rates led to a 60% increase in lung collagen content by 300 days (control: 3·05 ± 0·24 mg/lung, ²³⁹PuO₂-exposed: 4·88 ± 0·42 mg/lung). The data suggest that extensive remodelling of the lung connective tissue matrix occurs during development of fibrosis and that, over long periods of time, small imbalances between synthesis and degradation may result in quite large increases in protein content.     

Long-term consequences of 239PuO2 exposure in dogs: persistent T lymphocyte dysfunction.

Young Beagle dogs were exposed by inhalation to aerosols of 239PuO2 and observed for their lifespans as part of a large, ongoing study of the biological effects of inhaled radionuclides. The purpose of our study was to compare certain immune responses of the 239PuO2-exposed dogs at middle age (7-10 years old) and old age (12-14 years old), with those of unexposed, age-matched or young (3-4 years old) animals. Some of the aged, exposed dogs had developed lung tumours. Lymphocyte proliferative responses to phytohaemagglutinin (PHA) were lower in aged control dogs than in either young or middle-aged control dogs. Both aged and middle-aged, radiation-exposed dogs had decreased responses to PHA when compared to age-matched controls. Responses to concanavalin A (Con A) were not affected by age in control dogs, but tended to decrease in the oldest group of radiation-exposed dogs. Responses to both PHA and Con A were severely depressed in tumour-bearing dogs. The cytolytic activity of natural killer cells was not affected by age, radiation exposure, or tumour presence. We concluded that inhalation of 239PuO2 by young Beagle dogs resulted in an earlier-than-normal decrease in the ability of T cells to respond to mitogenic stimulation. In other words the depressed responses to PHA that were observed might represent radiation-induced, accelerated ageing of the T cell response.     

SEM autoradiography: aggregation of inhaled 239PuO2

Aggregation of inhaled 239PuO2 particles in the pulmonary region of the lung may be required for promotion of pulmonary carcinogenesis in rats. Female Wistar rats were exposed to an aerosol of 239PuO2 and their lungs examined by scanning electron microscopic (SEM) autoradiography. SEM autoradiography provides a rapid and inexpensive method for viewing a large lung tissue volume for alpha tracks. Evidence of particle aggregation was seen by 28 days postinhalation and was marked by 90 to 150 days post-inhalation. Subpleural plutonium particles resulted in exposure into the pleural cavity. Peribronchiolar, alveolar plutonium particles and particle aggregates gave the greatest radiation dose to the bronchiolar epithelium. High-dose, overlapping, alpha-track, radiation zones in bronchiolar epithelium may be required for maximum development of lung tumors.     

Collagen metabolism in rat lungs during chronic intermittent exposure to oxygen.

Collagen metabolism was studied in rat lungs during prolonged intermittent exposure to oxygen. After an initial of 2-d exposure to oxygen, the rats alternately breathed air and oxygen in 24-h periods up to 30 d. Lung histology showed perivascular edema as an early sign of oxygen toxicity. Increased capillary permeability was followed by a marked perivascular leukocytosis that was prominent between the 5th and 11th d of the treatment. During the further course of the experiment, the inflammatory response gradually diminished, and finally a network of collagen fibres filled the perivascular areas. The inflammatory process elevated the amounts of DNA and RNA in lung tissue, and the ratio of RNA to DNA was maximal on the 5th day. Studies on metabolism of lung collagen with intraperitoneally injected 3H-proline as label showed that, after the initial inflammatory reaction, both synthesis and degration of collagen were increased in oxygen-treated lungs. The increase in synthesis exceeded the rise in degradation and, therefore, collagen was accumulated. The activation of lung collagen synthesis coincided in time with a rise in the activity of lung protocollagen proline hydroxylase.     

Pulmonary immune response of dogs after exposure to 239PuO2

This study evaluated the cell-mediated (CMI) and humoral immune responses in four Beagle dogs five to six years after single inhalation exposures to different monodisperse 239PuO2 aerosols (0.72-1.4 microns activity median aerodynamic diameter). These exposures resulted in initial lung burdens ranging from 19 to 35 kBq. Four nonexposed dogs were used as age-matched controls. Anesthetized dogs were immunized by instillation of sheep red blood cells (SRBC) into selected lung lobes. Cells and fluids were obtained serially from blood samples and by bronchoalveolar lavage of the saline- and SRBC-treated lung lobes at 5-20 days after immunization. The CMI response evaluated by the leukocyte procoagulant activity test was similar in the saline- and SRBC-treated lobes of both groups of dogs. The humoral immune response was measured by the enzyme-linked immunosorbent assay. No differences were shown between the amount of antibody measured in the sera or lung lavages from control or Pu-exposed dogs. Histopathology of the tracheobronchial lymph nodes from the Pu-exposed dogs showed them to be fibrotic with no lymphoid cells, suggesting that these tissues could not respond to the antigen deposited in the lungs. However, both mediastinal and sternal lymph nodes did contain lymphoid tissue, and were likely to be the lymphoid tissues that produced the immunity to the antigen deposited in the lungs of the exposed dogs. Although both exposed and control dogs produced immune responses to the antigen instilled into their lungs, differences were observed in the number of neutrophils in lung lavages from the control and exposed animals. There was a dramatic influx of neutrophils into both the saline- and SRBC-treated lung lobes of the Pu-exposed dogs that was not seen in the age-matched controls. This suggests that the inhaled 239PuO2 produced chronically-active inflammation in the lung which may contribute to recruitment of lymphocytes to the lung following intrapulmonary deposition of antigen. In conclusion, the immune responses induced by lung immunization of dogs that had inhaled 239PuO2 were not suppressed by large doses of chronic alpha irradiation of the lungs and tracheobronchial lymph nodes, indicating that local pulmonary immune responses are preserved despite severe radiation-induced alteration of these tissues.     

Survival,lung clearance,dosimetry and gross pathology of rats exposed to either NpO 2 or PuO 2 aerosols

Purpose : To compare survival, lung dosimetry and gross pathology after inhalation exposure of rats to either NpO 2 or industrial PuO 2 aerosols with similar granulometric parameters. Because the specific alpha activity ratio Pu/Np is about 600, a much more homogeneous lung irradiation was expected for NpO 2. Materials and methods : Male Sprague Dawley rats were exposed once and their lung burdens were measured by X-ray spectrometry at different times post-exposure up to death. The time-course of doses delivered to the lungs were estimated, taking into account individual lung clearance parameters and body and lung weights. Gross lung pathologies were scored at autopsy. Results : In the range of initial lung deposits (ILD) studied (0.1-4 kBq), lung clearance impairment and reduced lifespan were only observed after exposure to NpO 2. For similar ILD or doses, the highest incidences of lung lesions assumed to be tumours were observed for NpO 2 with a saturation of lung tumour induction for doses larger than 8 Gy (ILD: 1.5kBq). Up to 22Gy (ILD: 3.5kBq), such saturation was not observed for PuO 2. Conclusions : NpO 2 appears much more toxic than PuO 2. Before saturation, lung tumour incidence increased nearly linearly with dose, the slope of the curve for NpO 2 being about twice as steep as that for PuO 2     

Survival, lung clearance, dosimetry and gross pathology of rats exposed to either NpO2 or PuO2 aerosols

PURPOSE: To compare survival, lung dosimetry and gross pathology after inhalation exposure of rats to either NpO2 or industrial PuO2 aerosols with similar granulometric parameters. Because the specific alpha activity ratio Pu/Np is about 600, a much more homogeneous lung irradiation was expected for NpO2. MATERIALS AND METHODS: Male Sprague Dawley rats were exposed once and their lung burdens were measured by X-ray spectrometry at different times post-exposure up to death. The time-course of doses delivered to the lungs were estimated, taking into account individual lung clearance parameters and body and lung weights. Gross lung pathologies were scored at autopsy. RESULTS: In the range of initial lung deposits (ILD) studied (0.1-4 kBq), lung clearance impairment and reduced lifespan were only observed after exposure to NpO2. For similar ILD or doses, the highest incidences of lung lesions assumed to be tumours were observed for NpO2 with a saturation of lung tumour induction for doses larger than 8 Gy (ILD: 1.5kBq). Up to 22Gy (ILD: 3.5kBq), such saturation was not observed for PuO2. CONCLUSIONS: NpO2 appears much more toxic than PuO2. Before saturation, lung tumour incidence increased nearly linearly with dose, the slope of the curve for NpO2 being about twice as steep as that for PuO2.     

Comparative biokinetics of plutonium and americium after inhalation of PuO2 and mixed oxides (U, Pu)O2 in rat

PURPOSE: To compare the biokinetics of Pu and Am in rat after inhalation of PuO2 and two (U, Pu) mixed oxides (MOX), referred to as MIMAS and SOLGEL. MATERIALS AND METHODS: Lung clearance was measured in vivo by X-and y-ray spectrometry. Retention of Pu and Am in femurs, liver and kidneys was measured by alpha-spectrometry. RESULTS: Observed lung clearance was in the same range for all three powders. Extra-pulmonary transfers were expressed as the percent of the initial deep lung deposit (IDLD) measured 7 days after inhalation. After PuO2 exposure, bone retention remained nearly constant throughout the 270-day experiment. It was approximately 0.7% of the IDLD for Pu and Am. By contrast, a gradual increase was observed for the two MOX. After 7 days, bone retention of Pu and Am was respectively 0.05 and 0.08% for MIMAS, and 0.2 and 0.6% for SOLGEL. The retention reached maximal values between 180 and 270 days post-exposure, which were 0.2 and 0.3% for MIMAS, and 1.2 and 2.8% for SOLGEL for Pu and Am respectively. CONCLUSIONS: Different transfer rates of Pu and Am from the lung were observed depending on the chemical composition of the oxides and/or the method of their preparation.     

Effect of inhaled 239PuO2 on alveolar type II cells

Morphological changes of rat alveolar type II (AT-II) cells were studied at 8 and 10 months following inhalation of 239PuO2 to elucidate the biological role of AT-II cells in the induction of lung tumours. TEM micrographs of random sections of lung were analysed qualitatively and quantitatively using an automatic image analyser. Eighteen morphometric parameters were obtained according to stereological principles. The results showed that, following the inhalation of 239PuO2, AT-II cells became less differentiated and the metabolism of the pulmonary surfactant in AT-II cells was disturbed.     

Uptake of cis-4-[18 F]fluoro-L-proline in scar formation: a marker of collagen synthesis?

Excessive scar formation is accompanied by abnormal collagen synthesis. The feasibility of monitoring collagen synthesis in vivo with no-carrier-added cis-4[18F]fluoro-L-proline (cis-FPro) was evaluated in an animal model with scar formation induced by implanted meshes. The abdominal wall of rats was replaced by alloplastic meshes. At days 3, 7, 14, 21 and 90 after implantation, the uptake of cis-FPro at 4 h post-injection was determined for resected samples of the mesh and normal tissues. The highest uptake was found in the kidneys (1.73+/-0.47%ID/g) followed by the liver (0.59+/-0.19%ID/g). The meshes showed the maximum uptake at day 3 (0.20+/-0.07%ID/g) with a decrease to 0.10+/-0.03%ID/g at day 90 (P<0.001). After 3 days no connective tissue was shown by histopathological morphometric analysis. The maximum partial volume (PV%) of connective tissue was 43+/-14 PV% 90 days after implantation. The maximum levels of granulocytes and inflammatory infiltrate were found at day 3 with minimal levels at day 90, paralleling the course of cis-FPro uptake. In conclusion, the uptake of cis-FPro at 4 h post-injection is not related to the content of connective tissue. Cis-FPro radiolabelled with 18F appears not to be a suitable radiopharmaceutical for in vivo monitoring of collagen synthesis in scar formation.     

Acute and repeated inhalation lung injury by 3-methoxybutyl chloroformate in rats: CT-pathologic correlation

OBJECTIVES: To investigate the acute and repeated pulmonary damage in Sprague-Dawley rats caused by the inhalation of 3-methoxybutyl chloroformate (3-MBCF) using computed tomography (CT), and to correlate these results with those obtained from a pathological study. METHODS: Sixty, 7-week-old rats were exposed to 3-MBCF vapor via inhalation (6 h/day) for 1 day (N=20), 3 days (N=20), and 28 days (5 days/week) (N=20) using whole body exposure chambers at a concentration of 0 (control), 3, 6 and 12 ppm. CT examinations including densitometry and histopathologic studies were carried out. For the follow-up study, the rats exposed for 3 days were scanned using CT and their pathology was examined at 7, 14, and 28 days. RESULTS: There was a significant decrease in the parenchymal density in the groups exposed to the 3-MBCF vapors for 1 day at 3 ppm (p=0.022) or 6 ppm (p=0.010), compared with the control. The parenchymal density of the rats exposed to 12 ppm was significantly higher. The pathological findings in this period, the grades of vascular congestion, tracheobronchial exfoliation, and alveolar rupture were significant. In the groups exposed for 3 days, there was a large decrease in the parenchymal density with increasing dose (control: -675.48+/-32.82 HU, 3 ppm: -720.65+/-34.21 HU, 6 ppm: -756.41+/-41.68 HU, 12 ppm: -812.56+/-53.48 HU) (p=0.000). There were significant density differences between each dose in the groups exposed for 28 days (p=0.000). The CT findings include an irregular lung surface, areas of multifocal, wedge-shaped increased density, a heterogeneous lung density, bronchial dilatation, and axial peribronchovascular bundle thickening. The histopathology examination revealed the development of alveolar interstitial thickening and vasculitis, and an aggravation of the mainstem bronchial exudates and bronchial inflammation. The alveolar wall ruptures and bronchial dilatation became severe during this period. On the follow-up study, the groups exposed for 3 days showed diffusely increased parenchymal density on the 7 days study, but the lung densities were lower at 14 and 28 days than at 3 days. In the rats exposed to lowest concentration, the pulmonary parenchymal density and pathologic findings rapidly returned to normal within 1 week. CONCLUSIONS: Decreased parenchymal density of the lung was a common CT finding in acute and repeated inhalation injury. The air accumulation is believed to be the results of tracheolaryngeal inflammatory edema, bronchial dilatation, and alveolar rupture from the early period.     

Eccentric rehabilitation exercise increases peritendinous type I collagen synthesis in humans with Achilles tendinosis

It has been shown that 12 weeks of eccentric heavy resistance training can reduce pain in runners suffering from chronic Achilles tendinosis, but the mechanism behind the effectiveness of this treatment is unknown. The present study investigates the local effect of an eccentric training regime on elite soccer players suffering from chronic Achilles tendinosis on the turnover of the peritendinous connective tissue. Twelve elite male soccer players, of whom six suffered from unilateral tendinosis and six were healthy controls, participated in this study. All participants performed 12 weeks of heavy-resistance eccentric training apart from their regular training and soccer activity. Before and after the training period the tissue concentration of indicators of collagen turnover was measured by the use of the microdialysis technique. After training, collagen synthesis was increased in the initially injured tendon (n=6; carboxyterminal propeptide of type I collagen (PICP): pre 3.9+/-2.5 microg/L to post 19.7+/-5.4 microg/L, P<0.05). The collagen synthesis was unchanged in healthy tendons in response to training (n=6; PICP: pre 8.3+/-5.2 microg/L to post 11.5+/-5.0 microg/L, P>0.05). Collagen degradation, measured as carboxyterminal telopeptide region of type I collagen (ICTP), was not affected by training neither in the injured nor in the healthy tendons. The clinical effect of the 12 weeks of eccentric training was determined by using a standardized loading procedure of the Achilles tendons showing a decrease in pain in all the chronic injured tendons (VAS before 44+/-9, after 13+/-9; P<0.05), and all subjects were back playing soccer following the eccentric training regime. The present study demonstrates that chronically injured Achilles tendons respond to 12 weeks of eccentric training by increasing collagen synthesis rate. In contrast, the collagen metabolism in healthy control tendons seems not to be affected by eccentric training. These findings could indicate a relation between collagen metabolism and recovery from injury in human tendons.     

Malnutrition and oxygen at high pressure: influence on collagen synthesis in lung and heart of the newborn rat

Rat dams were divided into a malnourished group fed 6% protein and a control group fed 25% protein. Newborns were selected from the two groups for injection with 14C-proline. Half of those injected were exposed to oxygen averaging 60 psig. Malnutrition impaired collagen synthesis in the lung as early as day 10 and in the heart at day 5. At day 20 and 30, pups from malnourished dams showed less severe convulsion than did the controls. Malnourished group displayed less adverse effect on lung and heart relative to body weight than did controls. Lung and heart collagen content in the malnourished group at days 15 and 10, respectively, were less than the controls. Between day 5 and day 20, OHP does not affect the metabolism of the lung and heart connective tissues, but it does by day 30. Malnutrition affects collagen metabolism of the heart earlier than it does the lung.     

Ornithine decarboxylase in organs of rat following chronic gamma-irradiation at low dose-rates

PURPOSE: To investigate the consequence of continuous low dose-rate exposure to gamma-rays on ornithine decarboxylase (ODC EC 4.1.1.17) activity in organs of rat. MATERIALS AND METHODS: Young male Wistar rats were irradiated at 1.1, 2.1 and 12.9 cGy/day in the dose ranges of 9-165, 17-315 and 100-2000 cGy, respectively, in a specially designed chamber. ODC activity was determined in 20000 g supernatant fluid of thymus, spleen and lung by measuring the release of 14CO2 from L-[1-14C]ornithine. RESULTS: Chronic y-irradiation modulated ODC activity. It decreased at low cumulated doses (after 8 and 15 days of exposure). At longer periods after chronic irradiation (after 45 and 90 days), ODC activity was restored up to control levels despite increasing values of cumulated doses. On day 150 a similar increase in ODC activity in spleen 2.1 cGy/day and in lung at 12.9 cGy/day was observed. CONCLUSIONS: These studies showed a non-monotonic pattern of the 'dose-response' curve. The results were interpreted in terms of the triggering of a homeostatic system.     

Composition and turnover of contractile proteins in volume-overtrained skeletal muscle

The purpose of this study was to find the composition shift of myosin heavy chain (MyHC) isoforms in overtraining in fast- and slow-twitch skeletal muscles and different changes in MyHC isofom composition, synthesis and turnover rate between 4-week and 6-week overtraining. Male Wistar rats were randomly assigned to 4-week and 6-week endurance training, 4-week and 6-week overtraining groups. Plantaris (Pla), extensor digitorum longus (EDL), and soleus (Sol) muscles were studied. Daily excretion of 3-methylhistidine (3-MeHis) pool as an indicator for protein degradation increased in the 4-week and 6-week overtraining group to 4.04 +/- 0.21 and 4.32 +/- 0.23 %/day subsequently in comparison with the control group (2.16 +/- 14 %/day, p < 0.001). In Pla muscle MyHC I isoform synthesis rate was 33 200 +/- 2150 (after 6-week overtraining 27 100 +/- 1800, p < 0.05), IIa 32 600 +/- 2100; IId 27 300 +/- 1890 and IIb isoform 20 100 +/- 1600 (after 6-week overtraining 15 500 +/- 1400, p < 0.05) dpm/M leucine/min. Actin synthesis rate increased in fast-twitch muscles during 4- and 6-week overtraining, and in soleus muscle during 6-week overtraining. In EDL and Sol muscle MyHC isoform composition during 6-week overtraining did not change significantly. During the 6-week overtraining the relative content of MyHC I and IIb isoforms decreased and IIa and IId isoforms increased in Pla muscle. The initial increase of MyHC IIb isoform after 4-week overtraining shows the higher stability of this isoform in comparison with MyHC I isoform in fast-twitch muscles during high volume exercise.     

Ginkgo biloba extract prevents high altitude pulmonary edema in rats

Ginkgo biloba reduces the severity of acute mountain sickness in humans, but protection against high altitude pulmonary edema (HAPE) has not been reported. This study was conducted to determine if G. biloba would prevent early HAPE in rats. Six rats (ginkgo group) received G. biloba (200 mg/kg body weight in drinking water and an equal amount in peanut butter) for 2 days before and during high altitude exposure (380 mmHg pressure for 24 h). Six other rats (control group) received water and peanut butter alone. Protein concentrations in bronchoalveolar lavage fluid (BALF) were increased in control rats (19.8 +/- 2.6 mg/dL) compared to ginkgo rats (11.6 +/- 0.9 mg/dL; p = 0.014), demonstrating that untreated (control) rats developed mild HAPE following high altitude exposure. For comparison, BALF protein concentrations in sea-level rats (air group) given peanut butter were 12.6 +/- 0.8 mg/dL (n = 6). Although pleural effusions did not develop in any rats, the protein concentrations of pleural fluid were also increased in control rats (4.9 +/- 0.16 g/dL) compared to ginkgo rats (4.0 +/- 0.13; p = 0.001); air group: 3.5 +/- 0.08 g/dL. There were no differences in wet/dry lung weight ratios between groups, but wet left lung weights/preexposure body weight were increased in control rats (1.26 +/- 0.02 g/kg) compared to the ginkgo group (1.17 +/- 0.01 g/kg; p = 0.002); air group: 1.11 +/- 0.03 g/kg. In conclusion, the data show that G. biloba prevents the development of early HAPE in rats.     

Evaluation of risk factors for lung tumour induction in rats exposed to either NpO 2 or PuO 2 aerosols

Purpose : To compare the incidence of each lung tumour type after inhalation exposure of rats to either NpO 2 or industrial PuO 2 aerosols, which have a similar size. Materials and methods : Male Sprague-Dawley rats were exposed once and followed during their whole life span. At the end of their life, the whole lungs were fixed, embedded and cut into thin sections for histological analysis. The presence of tumours was evaluated on three distinct levels of the lobes for phenotype determination to establish dose-effect relationships. Results : In the range of lung doses studied (0.05 to more than 50 Gy), the general trend was an increased frequency of all types of tumours after inhalation exposure to neptunium compared with plutonium. The linearity of the lower part of the dose-effect relationships for all malignant lung tumours leads to the conclusion that NpO 2 is 3.3-fold more carcinogenic than PuO 2. Conclusions : According to a linear extrapolation of the data on malignant lung tumour incidence collected among all studies reported on actinide oxide carcinogenesis, the risk of lung tumour appears to vary over a factor of about 10 depending on the nature and/or size of the aerosol. This variation has to be taken into account for a realistic assessment of tumour risk.     

Evaluation of risk factors for lung tumour induction in rats exposed to either NpO(2) or PuO(2) aerosols

PURPOSE: To compare the incidence of each lung tumour type after inhalation exposure of rats to either NpO(2) or industrial PuO(2) aerosols, which have a similar size. MATERIALS AND METHODS: Male Sprague-Dawley rats were exposed once and followed during their whole life span. At the end of their life, the whole lungs were fixed, embedded and cut into thin sections for histological analysis. The presence of tumours was evaluated on three distinct levels of the lobes for phenotype determination to establish dose-effect relationships. RESULTS: In the range of lung doses studied (0.05 to more than 50 Gy), the general trend was an increased frequency of all types of tumours after inhalation exposure to neptunium compared with plutonium. The linearity of the lower part of the dose-effect relationships for all malignant lung tumours leads to the conclusion that NpO(2) is 3.3-fold more carcinogenic than PuO(2). CONCLUSIONS: According to a linear extrapolation of the data on malignant lung tumour incidence collected among all studies reported on actinide oxide carcinogenesis, the risk of lung tumour appears to vary over a factor of about 10 depending on the nature and/or size of the aerosol. This variation has to be taken into account for a realistic assessment of tumour risk.     

手掌参醇提物对染矽尘大鼠肺组织Ⅰ、Ⅲ型胶原合成的影响

 目的 探讨手掌参醇提物(GcEE)对染矽尘大鼠肺组织Ⅰ、Ⅲ型胶原合成的影响,阐明其抗矽肺纤维化的作用.方法 32只大鼠随机分成对照组、染矽尘组、GcEE治疗组和汉防己甲素(TT)组.建立矽肺动物模型后第2天起,GcEE治疗组、TT治疗组分别灌胃给予GcEE[8 g/(kg·d)]、TT[50 mg/(kg·3 d) ]治疗,对照组和染矽尘组给予等容蒸馏水,给药28 d后处死大鼠,观察肺组织Ⅰ、Ⅲ型胶原合成,并用图像分析系统进行定量分析.结果 GcEE可显著降低染矽尘 大鼠肺系数,减少肺组织Ⅰ、Ⅲ型胶原合成.结论 GcEE能够明显抑制染矽尘大鼠的肺纤维化.     

Influence of oxygen flow rate on signal and T(1) changes in oxygen-enhanced ventilation imaging

PURPOSE: To investigate the optimal oxygen flow rate for oxygen-enhanced MR ventilation imaging. MATERIALS AND METHODS: Using a cardiac-triggered nonselective inversion recovery (IR) half Fourier single-shot fast spin echo sequence, series of images were acquired with the subject alternately inhaling room air and 100% oxygen. Oxygen flow rates of 5 L/min, 10 L/min, 15 L/min, 20 L/min, and 25 L/min were studied, and signal intensity from the oxygen-enhanced ventilation images and T(1) of the lung were measured. RESULTS: The average signal intensity was 63.0 +/- 21.0 for 5 L/min, 98.7 +/- 26.8 for 10 L/min, 133.8 +/- 20.0 for 15 L/min, 138.7 +/- 19.7 for 20 L/min, and 139.2 +/- 37.9 for 25 L/min. The average T(1)'s of the lung were 1399 msec +/- 130 msec for room air, 1314 msec +/- 101 msec for 5 L/min, 1276 msec +/- 105 msec for 10 L/min, 1207 msec +/- 71 msec for 15 L/min, 1206 msec +/- 90 msec for 20 L/min, and 1207 msec +/- 42 msec for 25 L/min. CONCLUSION: The optimal flow rate is 15 L/min for oxygen-enhanced ventilation imaging.