摘要
目的探讨采用小动物正电子发射计算机断层显像(PET)-计算机体层扫描(CT)动态观察活体大鼠矽肺模型的可行性。方法无特定病原体级SD大鼠分为模型组和对照组,模型组一次性气管内注入质量浓度为30 g/L的矽尘混悬液建立大鼠矽肺模型,对照组予等体积的0.9%氯化钠溶液。2组大鼠均于造模后第1、2、3、4、6、8和12周分别随机选取6只,以小动物PET-CT进行肺部CT检查并检测CT值,同时进行PET检查并检测氟-18-氟代脱氧葡萄糖标准化摄取值(SUV)。扫描后处死大鼠,检测肺脏脏器系数,进行肺脏病理组织学观察,检测血清转化生长因子β1(TGF-β1)、白细胞介素1(IL-1)和肺组织羟脯氨酸(HYP)水平。结果模型组大鼠肺脏病理组织学改变在早期表现为肺组织炎症性渗出,随着时间延长,炎症反应逐渐减轻,而肺间质纤维化逐渐明显;PET-CT影像学表现与病理组织学改变基本一致。模型组大鼠肺部SUV在第1~3周3个时间点均高于同时间点对照组(P<0.05),且在第1~4周随染尘时间的增加而下降(P<0.05)。模型组大鼠肺部CT值在7个时间点均高于同时间点对照组(P<0.05),且在第1~6周随染尘时间的增加而下降(P<0.05),在第6~12周随染尘时间的增加而升高(P<0.05)。模型组大鼠肺脏脏器系数和肺组织HYP水平在7个时间点均高于同时间点对照组(P<0.05),且在第1~4周肺脏脏器系数随染尘时间的增加而下降(P<0.05),在第6~12周肺组织HYP水平随染尘时间的增加而升高(P<0.05)。除第3和4周外,模型组大鼠血清TGF-β1水平在其余5个时间点均高于同时间点对照组(P<0.05),且在第1~4周随染尘时间的增加而下降(P<0.05),在第4~8周随染尘时间的增加而升高(P<0.05);模型组大鼠血清IL-1水平在第1~4周4个时间点均高于同时间点对照组(P<0.05),且随染尘时间的增加而下降(P<0.05)。结论小动物PET-CT可有效观察活体矽肺模型大鼠肺部早期炎症和晚期纤维化,可作为动态追踪矽肺大鼠模型肺部损伤的检测方法。
Objective To explore the feasibility of dynamic observation and measurement of living silicosis rat model by using small animal positron emission tomography （PET）-computed tomography （CT）.Methods Specific pathogens free SD rats were divided into model group and control group.The silicosis rat model was established by one-time endotracheal injection of 30 g/L silica suspension, while the control group rats were injected of isopyknic 0.9% sodium chloride solution.Six rats from each group were randomly selected for CT scan from 1st, 2nd, 3rd, 4th, 6th, 8th and 12th week after silica injection using the small animal PET-CT.CT value and standardized uptake value （SUV） of 18F-fluorodeoxyglucose were measured.Lung tissue was collected for pathological sections.The levels of hydroxyproline （HYP） of lung tissue and serum transforming growth factor β1 （TGF-β1） and interleukin-1 （IL-1） were measured.Results Pathological sections of rats of model group showed inflammatory exudation, inflammation reduced and fibrosis increased with extended time.The results are identical with findings in PET-CT.Lung SUV of rats in model group in the 1st-3rd weeks were higher than that in control group in the same time point （P〈0.05） and decreased by the increasing time during the 1st-4 th weeks of dust injection （P〈0.05）.Lung CT values of model group in the 1st-12th weeks were higher than that of control group in the same 7 time points （P〈0.05） and decreased in the 1st-6th weeks and then increased in the 6th-12th weeks by the increasing time of dust injection （P〈0.05）.Lung coefficients and HYP levels of model group in the 7 time points were higher than that of control group in the same 7 time points （P〈0.05）.Lung coefficients decreased in 1st-4th weeks and lung HYP levels increased in 6th-12th weeks with the increasing time of dust injection （P〈0.05）.Excepted of the 3rd and 4th weeks, serum TGF-β1 levels of model group in other 5 time-points were higher than that of control group in the same 5 time points （P〈0.05） and decreased in the 1st-4th weeks （P〈0.05） then increased in the 4th-8th weeks （P〈0.05） by the increasing time of dust injection.Serum IL-1 levels of model group in the 1st-4th weeks were higher than that of control group in the same 4 time points （P〈0.05） and decreased by the increasing time of dust injection （P〈0.05） and decreased by the increasing time of dust injection （P〈0.05）.Conclusion Early inflammation and terminal fibrosis of living silicosis rat model could be observed effectively by small animal PET-CT, which can be used as a new approach for dynamic tracing silicosis in rat models.
出处
《中国职业医学》
CAS
北大核心
2017年第3期245-252,共8页
China Occupational Medicine
基金
国家科技支撑计划项目(2014BAI12B01)
国家自然科学基金(81302396)
国家临床重点专科建设项目(2011-09)
广东省科技计划项目(2017A020215159)
广东省医学科研基金(B2016056)
广东省职业病防治重点实验室(2012A061400007)
