Bone marrow-derived mesenchymal stem cells attenuate phosgene-induced acute lung injury in rats

Abstract

Accidental phosgene exposure could result in acute lung injury (ALI), effective therapy is needed for the patients with phosgene-induced ALI. As a type of cells with therapeutic potential, mesenchymal stem cells (MSCs) have been showed its efficacy in multiple diseases. Here, we assessed the therapeutic potential of MSCs in phosgene-induced ALI and explored the related mechanisms. After isolation and characterization of rat bone marrow MSCs (BMMSCs), we transplanted BMMSCs into the rats exposed to phosgene and observed significant improvement on the lung wet-to-dry ratio and partial oxygen pressure (PaO₂) at 6, 24, 48?h after phosgene exposure. Histological analyses revealed reduced sign of pathological changes in the lungs. Reduced level of pro-inflammatory tumor necrosis factor α and increased level of anti-inflammatory factor interleukin-10 were found in both bronchoalveolar lavage and plasma. Significant increased expression of epithelial cell marker AQP5 and SP-C was also found in the lung tissue. In conclusion, treatment with MSC markedly decreases the severity of phosgene-induced ALI in rats, and these protection effects were closely related to the pulmonary air blood barrier repairment and inflammatory reaction regulation.     

Air Pollution and Postneonatal Mortality in a Tropical City: Kaohsiung,Taiwan

With growing evidence of the association between daily mortality and air pollution in adults, it is important to investigate whether infants are also susceptible to the adverse health effects of ambient air pollutants. The purpose of this study is to examine the relationship between air pollution and postneonatal mortality in Kaohsiung, Taiwan, a large industrial city with a tropical climate, during the period 1994–2000, using a case-crossover analysis. Case–crossover analysis provides an alternative to Poisson time-series regression for studying the short-term adverse health effects of air pollution. The air pollutants examined included particulate matter (PM₁₀), sulfur dioxide (SO₂), ozone (O₃), nitrogen dioxide (NO₂), and carbon monoxide (CO). The risk of postneonatal deaths was estimated to increase by 4.0% per 67 μg/m³ (the interquartile range in daily ambient concentration of PM₁₀) for PM₁₀, 1.8% per 17.84 ppb for NO₂, 5.1% per 0.31 ppm for CO, and 4.6% per 19.20 ppb for O₃. Although positive, none of these associations achieved statistical significance. The established link between air pollution levels and infant mortality may not be as strong in cities with tropical climates, although other factors such as differences in pollutant mix or the underlying health of the postneonates may explain the lack of a strong association in this study. Further studies of this type in cities with varying climates and cultures are needed.     

光气染毒对小鼠肝脏的损伤作用

目的:研究小鼠光气染毒对肝脏的损伤作用与枯否氏细胞的变化.方法:40只小鼠,雌雄各半,随机分为4组. 正常对照组小鼠以空气为对照,染毒组小鼠给予11.9 mg/L剂量的光气,时间为5 min, 染毒后2, 4, 8 h,测定各组小鼠肝脏的丙二醛(MDA)含量、总超氧化物歧化酶(T-SOD)活力、还原型谷胱甘肽(GSH)及染毒4 h后进行肝组织学和超微结构观察. 结果: 随着光气染毒后时间的延长,小鼠肝脏的MDA含量升高,GSH含量降低,T-SOD活力在染毒后2 h显著升高,与正常组差异显著(P<0.05);光镜下,光气染毒的肝组织肝细胞呈现空泡样变性. 电镜下,染毒肝细胞脂滴增多,肝脏出血,枯否氏细胞(KC)出现凋亡征象. 结论: 光气染毒可引起小鼠肝脏脂质过氧化,肝细胞脂肪变性、KC凋亡.     

不同浓时积光气致大鼠急性死亡及氧化损伤作用

目的观察不同浓时积(concentration×time,Ct)光气致大鼠急性死亡和氧化损伤的作用。方法雄性SD大鼠60只随机分为对照组和5个光气染毒组,Ct分别为3ml×3min,15ml×1min,7.5ml×2min,5ml×3min及10ml×3min(30ml/min)。染毒后观察24h,计算病死(比)率。免疫组化法测定染毒后24h的肝脏核转录因子(NF-κB)的表达。以无动物死亡组作为氧化损伤观察组,染毒后24h测定肺脏湿干比、血清和肝脏丙二醛(MDA)及超氧化物歧化酶(SOD)。结果(1)病死比:对照组(0/10)、3×3组(0/10)、15×1组(0/10)、7.5×2组(4/10)、5×3组(4/10)、10×3组(10/10);(2)NF-κB:除对照组外,染毒组均有表达,15×1组最明显;(3)氧化损伤:对照组、3×3组和15×1组无动物死亡,作为氧化损伤观察组。各组肺湿干比与对照组差异无统计学意义(P>0.05);15×1组肝脏MDA、肝脏和血清SOD较对照组升高(P<0.05);3×3组各指标与对照组比较差异无统计学意义(P>0.05)。结论Ct值相同时,染毒时间越长,中毒越重,表明光气吸入导致动物死亡的过程中,染毒时间的作用大于染毒浓度;而非致死剂量的光气吸入造成的炎性反应和氧化损伤则与染毒浓度密切相关。     

大鼠经光气染毒后肺组织不同时间点PPAR-γ表达的变化

背景与目的： 研究大鼠经光气染毒后,不同时间点肺组织中过氧化物酶体增殖体激活受体γ (PPAR-γ)的表达变化,以探讨PPAR-γ在光气致大鼠急性肺损伤中的作用。 材料与方法： 60只SD雄性大鼠随机分为对照组和光气染毒后5个不同时间点检测组,共6组。正常对照组大鼠以空气为对照,染毒组大鼠给予38.08 mg/L剂量的光气,时间为1 min,于染毒后1、3、6、12、24 h观察肺组织湿干比、肺组织病理,并采用RT-PCR、ELISA和Western-blot分别测定肺组织中TNF-α及PPAR-γ的mRNA和蛋白表达变化。 结果： 经光气染毒后随时间的增加,肺湿干比增加;病理显示肺组织呈急性肺损伤加重趋势。肺组织TNF-α mRNA及蛋白表达水平增加,PPAR-γ mRNA表达水平在染毒后1 h明显降低,3 h降到最低,1、3、6 h和12 h时均显著低于正常组(P<0.05)。染毒后PPAR-γ蛋白表达显著降低(P<0.05),3 h降到最低,以后逐渐升高。 结论： 光气染毒后大鼠肺组织PPAR-γ基因及蛋白表达显著降低,这可能与光气诱导肺组织发生的炎症反应有关。     

紫外线照射充氧自血回输治疗家兔光气急性中毒

目的：探讨紫外线照射充氧自血回输（UBIO）疗法对光气染毒家兔急性肺损伤的治疗作用。方法：家兔50只,随机分为5组（n=10）：正常对照组、中毒组、常规治疗组、UBIO治疗组及UBIO联合常规治疗（复合治疗）组。染毒后记录家兔生存时间,于6、24、48和72h抽取动脉血作血气分析,72h后处死,开胸取肺,测定肺湿干比（W/D）、肺水含量（LW）和肺系数（L/B）,留取部分肺组织作组织病理学检查。结果：UBIO治疗组及UBIO联合常规治疗组与常规治疗组比较,生存时间明显延长。家兔光气中毒后,中毒组肺水肿指标显著升高（P〈0.01）。但经UBIO治疗后,与中毒组比较,UBIO治疗组及复合治疗组肺水肿指标显著降低（P〈0.05）,常规治疗组肺水肿指标与中毒组比较差异无统计学意义（P〉0.05）;UBIO治疗组及复合治疗组动脉血PaO2及SaO2明显高于常规治疗组（P〈0.05）且肺组织损伤较轻。结论：UBIO能改善氧供和代谢,减轻光气中毒造成的急性肺组织损伤,为光气中毒提供新的治疗途径。     

骨髓间充质干细胞移植在光气吸入性肺损伤大鼠肺组织及血浆炎症因子的干预作用

目的：观察骨髓间充质干细胞（bone marrow derived mesenchymal stem cells, BMD-MSCs）移植对光气吸入性肺损伤大鼠肺组织及血浆炎症因子的干预作用。方法：96只雄性SD大鼠随机分为：空气对照组（A组）、BMD-MSCs干预对照组（AM组）、光气染毒组（PH组）、光气染毒后BMD-MSCs 干预组（PM组）,每组8只。染毒组按8.33 mg/L动态恒量染毒5 min。PM组染毒后即刻经尾静脉注射106 BMD-MSCs。4组分别于模型完成后6、24、48 h处死大鼠,取肺组织行病理检查及肺湿/干比、血气分析,取血浆行Bio-Plex细胞因子检测。结果：PH组较A组TNF-α浓度明显升高（P＜0.05）;PM组较PH组TNF-α浓度降低（P＜0.05）。PM组与PH组血浆IL-4浓度6 h、24 h均降低,以PM组下降更明显（P＜0.05）;48 h明显升高,以PM组升高更明显（P＜0.05）。PH组较A组IL-10浓度高（P＜0.05）;PM组较PH组IL-10浓度高（P=0.013）。结论：经尾静脉注射BMD-MSCs后可以使大鼠血浆中抗炎因子IL-4和IL-10逐渐升高,促炎因子TNF-α逐渐下降,提示其对光气致急性肺损伤大鼠肺具有保护作用。     

高氧液对急性光气中毒肺损伤保护作用的实验观察

目的观察家兔光气染毒后血气、生化指标及形态学的变化,研究高氧液对急性光气中毒性肺损伤的保护作用。方法18只新西兰大白兔随机分3组,每组6只,雌雄不拘。1组为空白对照组;另外2组动物吸入光气,其中一组(阳性对照组)静脉输入平衡盐,另一组(高氧液组)静脉输入高氧液,3组分别于实验的不同时间取血,测定动脉氧分压(PaO2)、血浆丙二醛(MDA)含量、超氧化物歧化酶(SOD)活力,8h后处死动物,取肺组织,测定肺组织中还原型谷胱甘肽(GSH)、氧化型谷胱甘肽(GSSG)含量,并做组织病理学检查。结果(1)高氧液组与阳性对照组动物光气中毒后血浆MDA含量都随实验时间的延长而升高,PaO2、SOD活力则呈下降趋势,肺组织GSH含量下降,GSSG含量升高。在1、3及8h时两组动物的血浆MDA含量、SOD活力及肺组织GSH、GSSG含量与空白对照组相比,差异有统计学意义(P<0.05或P<0.01)。(2)高氧液组在3、8h时(即在治疗后)PaO2分别为[(9.91±0.49)、(9.15±0.46)mmHg],均高于阳性对照组[(9.03±0.76)、(8.11±0.57)mmHg],差异有统计学意义(P<0.01);血浆MDA含量分别为[(3.66±0.35)、(5.31±0.15)μmol/L],均低于阳性对照组[(4.32±0.26)、(7.4±0.33)μmol/L],差异有统计学意义(P<0.01);红细胞SOD活力分别为[(237.37±29.96)、(208.10±18.80)NU/m     

Synthesis of covalent [14C]‐labeled diarylsulfonylurea (DASU) inhibitors of the processing and release of IL‐1

CP‐452,759 and CP‐470,947, two covalent [¹⁴C]‐labeled diarylsulfonylurea (DASU) inhibitors of the processing and release of IL‐1 from human monocytes, have been synthesized. The radiosyntheses utilize [¹⁴C]‐labeled phosgene to prepare labeled isocyanates which are coupled with an epoxide sulfonamide to give the [¹⁴C]‐DASUs. These tools should allow future studies aimed at purifying and identifying the DASU binding protein involved in the inhibition of the processing and release of IL‐1 from human monocytes. Copyright © 2002 John Wiley & Sons, Ltd.