汉防己甲素防治放射性肺损伤的临床观察

目的:观察汉防已甲素(Tet)防治放射性肺损伤的安全性疗效.方法:122例胸部放疗患者分为实验组(RT+Tet)52例,对照组(RT)70例.放疗均采用3D-CRT技术,DT56～70 Gy.肺V20控制在(20±6)%.实验组于放疗中每周1～6 d口服Tet 100 mg/次,3次/d.观察药物毒副反应和放射性肺损伤情况.结果:两组均顺利完成治疗计划,未发生药物相关不良反应.急性放射性肺损伤,实验组:0级20例,Ⅰ级29例,Ⅱ级3例.对照组:0级41例,Ⅰ级27例,Ⅱ级2例;晚期放射性肺损伤,实验组:0级41例,Ⅰ级9例,Ⅱ级2例.对照组:0级51例,Ⅰ级13例,Ⅱ级6例.两组急性和晚期放射性肺损伤发生情况,差异均无统计学意义,P值分别为0.083和0.536.对照组临床中激素应用率为39%(27/70),明显高于实验组19%(10/52),P=0.022.结论:Tet在胸部放疗中使用安全,对急性和晚期放射性肺损伤的防治作用尚未显现.激素的应用可能是观察放射性肺损伤的主要影响因素之一.     

碘油栓塞致大鼠肝肿瘤细胞凋亡和动态病理观察

目的　研究经肝动脉碘油灌注栓塞后大鼠肝肿瘤病理学表现 ,观察肿瘤细胞凋亡情况。方法　 4 1只Walker 2 5 6大鼠肝癌模型随机分为 6组 :对照组 6只大鼠经胃十二指肠肝动脉灌注 76 %泛影葡胺 0 .2～ 0 .3ml;实验组肝动脉灌注栓塞超液态碘油 0 .5ml/kg与泛影葡胺乳剂 (1∶1) ,按碘油栓塞后 0 ,1,3,5 ,10d分为 5组 ,每组 7只。光镜和透射电镜分别观察大鼠肝肿瘤组织病理 ,检测凋亡细胞。结果　与对照组比较 ,实验组大鼠的肿瘤增长率 (GR)受到抑制 ,栓塞 3d组GR为 2 8% ,对照组为 133%。 3～ 10d组肿瘤坏死程度加重 (P <0 .0 1) ,10d组有 1例完全坏死 ,栓塞后早期炎症反应明显 ,后期出现纤维包裹和分隔。 1～ 10d组有 17例大鼠的凋亡细胞计数为阳性 ,主要位于肿瘤周边 ,呈典型细胞凋亡形态学特征。结论　经肝动脉单纯灌注栓塞碘油可引起大鼠肝肿瘤不同程度坏死 ,诱导肿瘤细胞凋亡可能是其另一种重要作用机制。     

大鼠皮层C6脑胶质瘤模型的建立

目的 :为脑胶质瘤的研究提供实验基础 ,建立稳定可靠的动物模型。方法 :借助于脑立体定位技术 ,在 2 5只雄性Wistar大鼠脑S1区接种含有 10g L琼脂糖的C6细胞悬液。随机分成 4个周组和 1个自然死亡组后观察大鼠的生存期 ,并采用MRI、病理解剖、HE染色及GFAP免疫组织化学方法 ,动态观察各周组肿瘤生长情况。结果 :在不同周组中 ,所有检查均显示颅内肿瘤形成 ,GFAP阳性。 4周内无死亡 ,自然死亡组在第 5周死亡 2只、余 3只于第 6周死亡。结论 :该方法建立的S1区脑胶质瘤模型具备与人脑胶质瘤生长相似的特性 ,肿瘤形成时间短 ,生存期稳定 ,且无脑外转移和颅外扩散 ,适合各种脑胶质瘤实验治疗研究。     

热疗对放射性肺损伤保护作用的实验研究

目的:研究热疗对新西兰白兔放射性肺损伤的保护作用.方法:16只雄性实验兔随机分为单纯照射组(对照组)和热疗+照射组(实验组),所有实验兔右肺照射40 GY,实验组照射后1周行热疗,每周2次,共4次热疗.照射后6周和12周分别行胸部CT和SPECT肺灌注显像,12周后进行放射性肺损伤的病理学比较.结果:两组6周和12周时胸部CT比较差异无统计学意义,P>0.05;6周时肺灌注显像两组均未见放射性稀疏;12周时肺灌注显像,两组均见右肺放射性稀疏缺损,实验组右肺与全肺放射性计数比值较对照组高,差异有统计学意义,P<0.05;两组病理学改变差异无统计学意义.结论:热疗可减轻放射性肺损伤的发生程度.     

RGS5表达变化和大鼠胶质瘤生长的关系

目的 探讨G蛋白信号调节因子5 (regulator of G protein signaling 5,RGS5)表达变化与大鼠胶质瘤生长之间的关系.方法 72只Sprague-Dawley (SD)大鼠随机平均分为胶质瘤组、生理盐水组、健康对照组、腺病毒-大鼠增殖抑制基因-绿色荧光蛋白重组复合物(adenovirus-rat hyperplasia suppressor gene-green fluorescent protein,Adv-rHSG-GFP)组.胶质瘤组和Adv-rHSG-GFP组建立大鼠C6胶质瘤动物模型,生理盐水组颅内注射10 μL生理盐水,健康对照组为健康大鼠.Adv-rHSG-GFP组在接种C6胶质瘤细胞后第4和11天,于肿瘤原位注射重组腺病毒Adv-rHSG-GFP.接种C6胶质瘤细胞后第9、15和21天取脑胶质瘤观察肿瘤的生长情况,免疫组织化学法检测RGS5蛋白的表达.结果 Adv-rHSG-GFP组肿瘤体积小于胶质瘤组(P＜0.01).生理盐水组和健康对照组无肿瘤生长.接种后第15和21天胶质瘤组RGS5蛋白表达均高于生理盐水组、健康对照组和Adv-rHSG-GFP组(均P＜0.01).结论 RGS5高表达与大鼠胶质瘤生长密切相关.     

维甲酸及氟伐他汀对放射性肺损伤防治作用的实验研究

目的:观察维甲酸(RA)和氟伐他汀(Flu)对放射性肺损伤的防治作用.方法:雌性SD大鼠80只随机分为正常对照组、单纯照射组、治疗组和预防组.后3组麻醉后,行直线加速器全胸部照射.预防组于照射前7 d以RA、Flu各10 rag/(kg·d)灌胃;治疗组于照射后次日灌服RA、Flu各10 mg/(kg·d);另两组灌服等量生理盐水直至实验结束.分别于照射后5、15、30和60 d每组各取5只大鼠,观察肺组织标本HE染色和胶原纤维染色;肺组织TGF-β1免疫组化检测以计算机图像分析系统测定.结果:治疗组和预防组大鼠肺炎和肺水肿比单纯照射组明显减轻,胶原纤维含量也明显减少.单照组在照射后5、15、30和60 d肺组织TGF-γ1阳性面积与正常对照组比较逐渐增大,P<0.01;而治疗组和预防组与同期单照组比较明显减小,P<0.05;预防组在15和30 d与同期治疗组比较明显减小,P<0.01.结论:RA联合Flu能有效地减轻放射性肺炎,抑制胶原纤维增生.预防组较治疗组能更好地减轻放射性肺损伤.     

奥沙利铂致大鼠周围神经系统毒性的病理学研究

目的:探讨奥沙利铂致大鼠周围神经系统毒性损害的病理改变是否具有时间依赖性与药物剂量依赖性的特点。方法:利用光镜和透射电镜技术观察大鼠后根神经节(dorsal root ganglia,DRG)及坐骨神经在奥沙利铂不同应用剂量及不同作用时间点的病理改变,并利用图像分析系统对DRG的形态改变进行分析。结果:DRG内感觉神经元的细胞体、细胞核及核仁均有不同程度固缩,用药后24~48 h最为显著,5周后基本恢复。细胞体与细胞核的面积与药物剂量成线性关系(r2=0.957,P=0.001;r2=0.983,P=0.000),核仁面积与药物剂量成非线性关系(r2=0.984)。坐骨神经在用药后24 h可见轻微的髓鞘变性,5周后明显好转。结论:奥沙利铂周围神经系统毒性损害的靶器官主要为DRG,并以DRG内感觉神经元的核仁改变最为显著,周围神经的损伤很可能为继发性损伤,以上病理改变具有可恢复性及药物剂量依赖性的特点。     

胸部肿瘤三维适形放疗急性放射性肺损伤相关因素的分析

目的:分析三维适形放射治疗胸部肿瘤患者发生急性放射性肺损伤的临床、物理和生物学因素,为预测急性放射性肺损伤,优化放疗计划提供参考。方法:对84例胸部肿瘤放疗后发生急性放射性肺损伤的患者进行单因素和多因素Logistic回归及相关分析。采用双抗体夹心ELISA法检测放疗前、后的血浆转化生长因子-β1(TGF-β1)水平;从剂量体积直方图上获取放射物理数据。结果:84例患者中发生急性放射性肺损伤19例,其中Ⅰ级8例,Ⅱ级5例,Ⅲ级5例,Ⅳ级1例,急性放射性肺损伤的发生率为22.62%(19/84);单因素Lo-gistic回归分析显示与急性放射性肺损伤相关的因素有放疗前的肺功能(基础肺功能)、肺V20、化疗和放疗后的血浆TGF-β1升高,P<0.05。结果显示,放疗后总体血浆TGF-β1水平低于放疗前的水平。多因素Logistic回归结果显示,急性放射性肺损伤的独立危险因素为肺V20和基础肺功能(OR值分别为3.094、3.945)。结论:三维适形放射治疗胸部肿瘤时肺的V20和基础肺功能可能是引起急性放射性肺损伤的主要因素。放疗后血浆TGF-β1水平升高还不能作为预测急性放射性肺损伤的指标。     

视黄酸对放射性肺损伤大鼠肺组织CD36表达的影响

目的探讨视黄酸对放射性肺损伤肺组织病理改变和信号蛋白CD36表达的影响。方法将80只健康雄性Wistar大鼠随机分为4组：正常对照组（A组）、单纯给药组（B组）、单纯照射组（C组）和照射加给药组（D组）,每组20只。C、D两组大鼠行6MV-X线15 Gy全胸野照射,B、D两组大鼠给予20 mg/（kg.d）视黄酸制剂灌服。于照射后第1、2、4、8周行支气管肺泡灌洗,计数肺泡灌洗液细胞数,留取肺组织标本,作HE和Masson染色、免疫组织化学法检测CD36表达。结果 HE和Masson染色提示照射后的1周始肺泡腔有炎性细胞渗出,继之间质水肿,4及8周出现肺泡腔变小结构破坏,局部实变,肺间质出现胶原纤维;B组与A组比较各时间段的病理无明显差别,但D组与C组比较大鼠肺炎和肺水肿减轻,肺组织胶原纤维量减少。肺泡灌洗液的细胞总数C组与A组比较各时间段都明显增高（P〈0.01）,D组与C组比较,肺泡灌洗液总数降低,第4、8周差别有统计学意义（P〈0.005）。免疫组织化学检测示：A组与B组检测的4个时间点CD36表达差别均无统计学意义;C组和D组与A组比较在放疗后的第1、2、4、8周时间段CD36表达均明显增强（P〈0.0001）,以C组增强更明显;D组与C组比较CD36表达减弱,以第4、8周表达减弱更明显。结论放射性肺损伤时肺组织CD36表达明显增强,视黄酸对大鼠正常肺组织的CD36表达无影响,但它能从蛋白质水平有效抑制放射诱导的CD36表达,对放射性肺损伤有防治作用,为临床上用其治疗放射性肺损伤提供了实验依据。     

肺癌放化疗中放射性肺损伤的临床预测因素

放射性肺损伤是肺癌放化疗综合治疗中常见并发症,放化疗因素、临床因素在肺损伤中预测作用如何未有统一意见,剂量参数是目前唯一肯定的预测因子。     

Relating radiation-induced regional lung injury to changes in pulmonary function tests

PURPOSE: To determine whether the sum of radiotherapy (RT)-induced reductions in regional lung perfusion is quantitatively related to changes in global lung function as assessed by reductions in pulmonary function tests (PFTs). METHODS AND MATERIALS: Two hundred seven patients (70% with lung cancer) who received incidental partial lung irradiation underwent PFTs (forced expiratory volume in 1 s and diffusion capacity for carbon monoxide) before and repeatedly after RT as part of a prospective clinical study. Regional lung function was serially assessed before and after RT by single photon emission computed tomography perfusion scans. Of these, 53 patients had 105 post-RT evaluations of changes in both regional perfusion and PFTs, were without evidence of intrathoracic disease recurrence that might influence regional perfusion and PFT findings, and were not taking steroids. The summation of the regional functional perfusion changes were compared with changes in PFTs using linear regression analysis. RESULTS: Follow-up ranged from 3 to 86 months (median 19). Overall, a significant correlation was found between the sum of changes in regional perfusion and the changes in the PFTs (p = 0.002-0.24, depending on the particular PFT index). However, the correlation coefficients were small (r = 0.16-0.41). CONCLUSIONS: A statistically significant correlation was found between RT-induced changes in regional function (i.e., perfusion) and global function (i.e., PFTs). However, the correlation coefficients are low, making it difficult to relate changes in perfusion to changes in the PFT results. Thus, with our current techniques, the prediction of changes in perfusion alone does not appear to be sufficient to predict the changes in PFTs accurately. Additional studies to clarify the relationship between regional and global lung injury are needed.     

放射性肺损伤小鼠动物模型的建立与鉴定

目的:建立放射性肺损伤小鼠动物模型和有效的定量评价方法.方法:雄性昆明种小鼠36只,随机分作2组,对照组(12只)不做任何处理,照射组(24只)全肺单次照射18 Gy.于照射后2、6和12周,进行小鼠肺部螺旋CT扫描及图像分析,获得小鼠全肺的平均灰度值;采用HE染色法观察肺组织的变化.结果:照射后2、6和12周的CT图像分析表明,与正常对照组相比,照射组CT平均灰度值均上升,照射后2和6周差异有统计学意义,P值分别为0.003、0.006.与对照组相比,照射组小鼠的肺组织在照射后存在明显的病理组织学上的改变,早期以急性炎症为主,表现为肺充血、水肿、肺间质增厚,后期损伤以肺泡间隔的进行性纤维化为特征.结论:小鼠全肺单次照射18 Gy X射线可建立放射性肺损伤小鼠动物模型,用螺旋CT扫描,计算机软件UTHSCSA Image Tool 3.0灰度分析方法可以有效地定量评价早期放射性肺损伤程度.     

Effect of high-dose pentoxifylline on acute radiation-induced lung toxicity in a rat lung perfusion model

PURPOSE: The purpose of this study was to study the effect of high-dose oral pentoxifylline on radiation-induced acute lung injury as assessed with a rat lung perfusion model. METHODS AND MATERIALS: Adult male Sprague-Dawley rats were used throughout this study. A preliminary experiment determined that treatment with 2 g/liter pentoxifylline in drinking water resulted in an average consumption of 1.38 g/m2/day, which is comparable to the maximum tolerated dosage in humans. Seventy-two rats were irradiated to the left hemithorax with single fraction doses ranging from 10 through 18 Gy. Half were treated with 2 g/liter pentoxifylline in drinking water from 1 week before radiation through 8 weeks after radiation. Lung vascular perfusion scanning was performed at 3, 4, 5, 6, and 8 weeks after radiation using 99mTc-macroaggregated albumin. The lung perfusion ratio was defined as the number of counts due to radioactivity within the irradiated left lung region of interest divided by the number of counts within the region of the nonirradiated right lung. This lung perfusion ratio has been shown to decrease with radiation-induced lung injury. RESULTS: Although radiation led to a decreased lung perfusion ratio in all groups, those receiving pentoxifylline maintained higher ratios than irradiated controls from 3-5 weeks, especially for those receiving 15 or 18 Gy. However, from 6 through 8 weeks the irradiated controls exhibited partial recovery of lung perfusion ratio, whereas the pentoxifylline groups did not. By 8 weeks after 15 and 18 Gy, lung perfusion ratios were significantly higher for the irradiated controls than for pentoxifylline-treated rats-a reversal of the pattern observed at 3-5 weeks. CONCLUSIONS: The protection by pentoxifylline against radiation-induced acute lung injury was transient and limited to the first 5 weeks after radiation. Subsequent recovery from lung injury was inhibited by this drug at later times within the acute phase.     

放射性肺损伤的研究进展

放射性肺损伤是胸部恶性肿瘤放疗后常发生的一种严重并发症,其包括急性放射性肺炎和放射性肺纤维化。放射性肺损伤不仅限制肿瘤放疗剂量,还影响后续的治疗和患者的生存质量。放射性肺损伤发生机理的研究,大多数是在动物模型。众多的细胞、因子、分子等参与免疫应答调节,最终导致放射性肺损伤的发生。还有,对于放射性肺损伤的治疗尚无一个指南及规范,多凭借临床经验及专家委员会的权威意见。本文将对近几年有关放射性肺损伤的相关研究进行总结归纳,探究其病理生理及分子生物学变化、临床表现、影像学改变、诊治及预防。     

放射性肺损伤研究进展

目的:回顾和总结国内外放射性肺损伤的研究进展.方法:应用Pubmed和CNKI期刊全文数据库检索系统,以"胸部钟瘤、放射性肺损伤"为关健词,检索1998-01-2009-01有关放射性肺损伤的文献.纳入标准:1)放射性肺损伤的分子生学机制;2)放射性肺损伤的临床影响因素及防治.根据纳入标准分析34篇文献.结果:与放射性肺损伤的发生发展密切相关的细胞因子主要包括转化生长因子-β(TGF-β)、血小板源性生长因子(PDGF)和肿瘤坏死因子(TNF-a)等.剂量体积参数V20、V30、MLD和基础肺功能等成为预浏放射性肺损伤的因素,阿米福汀、还原型谷脱甘肽及中医中药对放射性肺损伤均有一定防治作用.结论:期待更有效的治疗方法应用于临床,减轻放射性肺损伤.     

LQB和qLQB模型的创建及在放射性肺损伤中的初步研究

目的 基于LQ模型建立LQB和qLQB模型,初步评估其放射性肺损伤中的有效性。方法 随机抽取45例胸部肿瘤患者资料,在医科达Precise 2.12 TPS上为每例患者设计计划,用定性LQB和LKB模型分别对计划优选结果进行评估。在定性LQB模型基础上建立定量LQB模型(qLQB模型),用qLQB模型计算上述优选计划的放射性肺损伤值,并将放射性肺损伤值与LKB模型计算的NTCP值进行配对t检验。结果 定性LQB和LKB模型对计划评估的吻合率为96%。qLQB模型计算的肺损伤值与LKB模型计算的NTCP值相近(P=0.412)。结论 LQB和qLQB模型在优选计划和评估放射性肺损伤方面与LKB模型有很好的一致性。     

探讨NSCLC放射性肺损伤NTCP模型的建立

目的 针对局部晚期NSCLC受累野IMRT后RILI发生情况,分析不同模型建模方法并评价其预测效果。方法 回顾分析2007-2011年间肿瘤医院收治的242例未进行手术治疗的Ⅲ期NSCLC患者临床资料。以放疗结束后6个月内发生2、3级RILI分别作为终点事件。分别采用PCA模型、LKB模型和MLD模型3种计算方法,对剂量学参数建立NTCP预测模型,并评价其预测效果。结果 PCA模型提取4个主成分,2、3级RILI预测结果,AUC分别为0.650、0.606。LKB模型2级RILI参数拟合得到m=0.46,n=1.35,D50=23.59 Gy,3级RILI参数拟合得到m=0.36,n=0.27,D50=72.67 Gy,AUC分别为0.607、0.585。MLD模型2、3级参数预测结果γ50=1.073,D50=24.66 Gy和γ50=0.97,D50=48.45 Gy,AUC分别为0.604和0.569。结论 使用相同治疗模式的单一人群大样本数据进行建模,对提高模型预测准确性和稳定性很重要。LKB模型和PCA模型均能较好地预测RILI的发生概率,MLD模型对3级RILI的预测效果较差。     

Relation between radiation-induced whole lung functional loss and regional structural changes in partial irradiated rat lung

PURPOSE: Radiation-induced pulmonary toxicity is characterized by dose, region, and time-dependent severe changes in lung morphology and function. This study sought to determine the relation between the structural and functional changes in the irradiated rat lung at three different phases after irradiation. MATERIALS AND METHODS: Six groups of animals were irradiated to 16-22 Gy to six different lung regions, each containing 50% of the total lung volume. Before and every 2 weeks after irradiation, the breathing rate (BR) was measured, and at Weeks 8, 26, and 38 CT was performed. From the computed tomography scans, the irradiated lung tissue was delineated using a computerized algorithm. A single quantitative measure for structural change was derived from changes of the mean and standard deviation of the density within the delineated lung. Subsequently, this was correlated with the BR in the corresponding phase. RESULTS: In the mediastinal and apex region, the BR and computed tomography density changes did not correlate in any phase. After lateral irradiation, the density changes always correlated with the BR; however, in all other regions, the density changes only correlated significantly (r(2) = 0.46-0.85, p < 0.05) with the BR in Week 26. CONCLUSION: Changes in pulmonary function correlated with the structural changes in the absence of confounding heart irradiation.