大鼠放射性肺损伤的高分辨率CT表现和转化生长因子-β、肿瘤坏死因子-α表达的相关性研究

目的 研究大鼠放射性肺损伤的高分辨率CT(HRCT)表现和血清转化生长因子B(TGF-β)、肿瘤坏死因子α(TNF-α)表达的相关关系,探讨细胞因子检测与HRCT检查对放射性肺损伤预测和早期诊断的价值.方法 48只Sprague-Dawley(SD)雄性大鼠采用完全随机方法分为8组,A组作为正常对照组,B～H组全肺单次剂量15 Gy 60 Co照射.于照射前、照射后1、2、4、8、12、16及24周分别依次取A～H组行HRCT扫描及酶联免疫法测定各组大鼠血清中细胞因子TGF-β、TNF-α水平,大鼠安乐死后取肺组织行病理观察.将同期HRCT征象、细胞因子水平及病理变化对照观察分析.组间平均水平比较运用t检验,相关性用Spearman等级相关分析.结果 HRCT扫描显示了7组大鼠放射性肺损伤发展过程中的4种征象:磨玻璃阴影1只、补丁实变影8只、大片实变影7只和纤维索条影3只.照射后1～24周各照射组大鼠血清中TGF-β平均水平[(3.33±0.47)、(3.20±0.65)、(3.12±0.45)、(3.54±0.80)、(3.30±1.13)、(2.49±0.67)、(4.19±0.22)μg/L]均较对照组平均水平[(0.45±o.14)μg/L]明显升高(P值均＜0.05);TGF-β平均水平至照射后24周升至最高值[(4.19±0.22)μg/L],与其他照射组比较差异有统计学意义(P值均＜0.05).照射后1～12周各照射组大鼠血清中TNF-α平均水平[(236.52±29.01)、(214.91±34.53)、(270.97±42.12)、(208.83±86.51)、(208.83±82.23)ng/L]均较对照组[(31.78±0.92)ng/L]明显升高(P值均＜0.05);TNF-α平均水平至第4周达到高峰[(270.97±42.12)ng/L],与其他照射组比较P值均＜0.05,至第16、24周明显降低[(60.63±38.49)、(32.07±1.05)ng/L],与对照组平均水平接近(P值均＞0.05).HRCT表现与TGF-β、TNF-α表达均无等级相关(r.分别为0.5570和0.1013),等级相关假设检验P＞0.05.病理变化与同期影像征象对照,两者相符合.结论 TGF-β、TNF-α变化早,提示血液中TGF-β、TNF-α的监测可以预测放射性肺损伤的发生.HRCT表现与TGF-β、TNF-α表达均无等级相关.

A correlation study between high resolution CT appearances and expression of transforming growth factor-β,tumor necrosis factor-α in radiation-induced lung injury of rats

Objective To study the correlation between high resolution computed tomography manifestations and expression of transforming growth factor beta,tumor necrosis factor alpha in radiationinduced lung injury of rats,and to investigate the vslues of cytokine detection and HRCT scanning for the prediction and early diagnosis of radiation-induced lung injury.Methods Forty-eight Sprague-Dawley (SD)rats were randomly divided into eight groups,group A was normal control group.and group BH were irradiated with a single dose of 15 Gy to the lungs.HRCT scanning Wag performed before and 1 week,2,4,8,12,16,24 weeks after radiation in group A-H respectively.The expression of TGF-beta and TNF-alpha were detected with ELISA. All the rats were killed to observe pathological changes of their lungs.HRCT signs,levels of cytokine were simultaneously compared and analyzed.The t-test and Spenrman rank correlation were used for the statistics.Results Four HRCT signs were observed during the 24 weeks after radiation,including ground-glass opacity(1 case),patchy consolidation(8 cases),massive consolidation(7 cases)and fibrosis(3 cases).The average levels of TGF-beta in group B-H[(3.33±0.47),(3.20±0.65),(3.12±0.45),(3.54±0.80),(3.30±1.13),(2.49±0.67),(4.19±0.22)μg/L,respectively]were hisher than the control group[(0.45±0.14)μg/L.P＜0.05].At 24 weeks the average level increased to the highest peak[(4.19 4-0.22)μg/L,P＜0.05].At 1 week and 2,4,8,12 weeks after radiation,the average level of TNF-alpha in radiation group[(236.52±29.01),(214.91±34.53),(270.97±42.12),(208.83±86.51),(208.83±82.23)ng/L]was hisher than the control group[(31.78±0.92)ng/L,P＜0.05].The average level increased to the highest peak [(270.97±42.12)ng/L,P＜0.05]at 4 weeks.The average level at 16 and 24 weeks[(60.63±38.49),(32.07±1.05)ng/L]dropped to the level similar to the control group(P＞0.05).There were no rank correlations between HRCT manifestations and expression of TGF-beta and TNF-alpha(rs=0.5570 and 0.1013.P＞0.05).HRCT signs were correlated with pathological changes.Conciusions The monitoring of TGF-beta and TNF.alpha in the serum after irradiation can predict the development of radiation-induced lung injury.There are no rank correlations between HRCT manifestations and expression of TGF-beta and TNF-alpha.