本文選題：放射性肺損傷 + 斷層掃描�。� 參考：《蘇州大學》2014年博士論文

【摘要】：第一部分雙源CT肺部灌注成像及其檢測放射性肺損傷的臨床意義 目的：針對胸部放療后的放射性損傷（radiation-induced lung injury, RILI）常規(guī)影像形態(tài)學改變出現(xiàn)較晚、臨床難以早期診斷的問題，胸部功能成像能否比傳統(tǒng)影像更早期反映RILI的功能變化？本研究探討應用雙源CT肺部灌注成像（CTperfusion imaging, CTPI）技術的可行性及其早期診斷RILI的臨床價值。 方法：選取臨床篩查肺動脈栓塞而行4D-CT增強檢查但影像診斷結果陰性以及臨床最終排除了肺部疾患的患者20例作為對照組，年齡47-76歲（男、女各10例）。實驗組為48例接受術后放療的上段食管癌或胸腺腫瘤患者(照射總劑量均為60Gy)，年齡43-70歲（男27例，女21例）。放療前及放療1/2總劑量時間點(30Gy)行CTPI檢查，同期檢測外周血中腫瘤壞死因子(TNF-α)、轉化生長因子(TGF-β1)，分析發(fā)生RILI(A組)與未發(fā)生RILI(B組)患者的血清細胞因子、常規(guī)CT表現(xiàn)及CTPI灌注值[相對血流量(rrBF)、相對血容量(rrBV)、相對毛細血管通透性(rrPS)]的變化，采用隨機區(qū)組設計t檢驗比較兩組間血清細胞因子、CTPI灌注值的差異，采用χ2檢驗比較常規(guī)CT與CTPI對RILI檢出的差異。使用西門子新雙源CT機（FLASH）肺部4D容積掃描技術作為CTP成像方法，先行常規(guī)高分辨率CT平掃（HRCT），后行灌注成像。 結果：⑴對照組所有20例患者均能獲得層次豐富、結構清晰的CTP圖像，肺野內(nèi)任意取不同大小的感興趣區(qū)（ROI），均能獲得重復性好的灌注值；正常成人肺的rBF、rBV及rPS平均值分別為149.3±18.3mL/100mL/min、14.86±2.65mL/100mL、9.54±2.91mL/100mL/min；肺部各灌注參數(shù)及密度值（HU）男女性別、左右部位差異均無統(tǒng)計學意義（P0.05）；上、下肺野ROI的rBF、rBV值有顯著差異（P0.05），上中肺野、中下肺野之間的各參數(shù)值無明顯差異（P0.05）。⑵48例患者中，18例發(fā)生RILl(A組)。A組外周血TNF-α和TGF-β1放療前后的差異無統(tǒng)計學意義(均P0.05)。放療1/2總劑量時，A、B兩組的外周血TNF-α、TGF-β1組間差異無統(tǒng)計學意義(均P0.05)；但A組常規(guī)CT圖像上有2例出現(xiàn)陽性征象。A組受照射肺組織rrBF、rrBV、rrPS均較照射前顯著增高(均P0.05)；B組的rrBF、rrBV較照射前有增高，差異有統(tǒng)計學意義(均P0.05)，rrPS無明顯變化(P0.05)；照射后A、B兩組rrBF、rrBV、rrPS間差異均有統(tǒng)計學意義（均P0.05）。根據(jù)ROC曲線，設rrPs=1.22為閾值，診斷RILl的敏感度、特異度分別為88.9％、90.0％，優(yōu)于HRCT的11.1％、90.0％(χ2=13.61,P0.05)。⑶對照組與實驗組放射治療前的各對應灌注值之間差異無統(tǒng)計學意義（P0.05）。 結論：⑴雙源CTPI技術能夠用于肺組織的灌注成像研究，能定量分析肺組織血流動力學參數(shù)（rBF、rBV、rPS等）。⑵外周血中TNF-α、TGF-β1變化對早期檢測腫瘤放療患者RILI的價值尚不確定。⑶CTPI能反映放療后肺組織血液動力學的變化，能早期反映RILI患者照射野的異常灌注，有可能成為早期檢出RILI的有效工具。 第二部分放射性肺損傷兔階梯模型的制備方法及鑒定 一、放射性肺損傷（RILI）兔階梯模型的制備 目的：針對人類放射性肺損傷（RILI）各期難以在臨床上準確把握以及難以進行生化、影像、組織病理等重復性研究，故建立一種適合動態(tài)觀測與研究的動物模型非常必要。本研究旨在探討放射性肺損傷（RILI）兔階梯模型的制備方法。 方法：健康新西蘭大白兔54只，隨機分作A組、B組及C組，每組各18只。三組均由同一麻醉師使用同樣的混合法麻醉技術，即先肌注地西泮（用量為0.8~1.0mL/kg），后肌注速眠新II號（用量為0.4~0.5mL/kg），然后經(jīng)自制中型動物醫(yī)學成像掃描床固定后作高能X線單側全肺單次照射，照射劑量分別35Gy、25Gy及15Gy，分別于照射后第1、2、3、4、5、6、8、12、16、20、24周進行階梯性常規(guī)CT觀察。重點觀察混合麻醉法的安全及有效性，以及比較各模型組出現(xiàn)CT陽性表現(xiàn)的時間及各組模型的總死亡率。 結果：⑴三組模型麻醉效果顯著，無意識的麻醉時間平均為30-40分鐘，麻醉死亡率均為零。⑵A、B、C三組模型常規(guī)CT出現(xiàn)滲出性毛玻璃影的高峰時間點分別為2周、4周、16周，并均在隨后的階梯時間點得到進一步的證實，即RILI的產(chǎn)生；模型中途死亡數(shù)分別為4只、1只、1只，死亡率分別為22.2%、5.6%、5.6%。 結論：混合法麻醉技術具有安全性高、重復性好、可控性強、易于操作等優(yōu)點。B組（25Gy）具有成模時間適中、死亡率低、階梯勻稱等優(yōu)勢，利于進一步的RILI階梯性分析，是首選的造模方法。 二、放射性肺損傷階梯模型的鑒定 目的：臨床上放射性肺損傷（RILI）的發(fā)生、發(fā)展的演變過程較為復雜，RILI的各期無明顯分界，因此對RILI動物模型的動態(tài)觀測及鑒定具有重要的臨床指導意義。故本研究旨在探討RILI兔階梯模型的動態(tài)血清學及組織病理學鑒定，以確定階梯模型的發(fā)生及演變過程。 方法：麻醉方法同上，采用上述25Gy造模方法，共計60只健康新西蘭大白兔經(jīng)高能X線單側全肺單次照射造模，設為實驗組。同時隨機同批次大白兔36只作假照射，設為為對照組，按下述照射后時間點分12個亞組，實驗及對照組的每個亞組分別為5只、3只。分別于照射后第1、6、12、24、48、72小時及第1、2、4、8、16、24周進行開胸暴露心臟后穿刺提取4-8mL全血以備血清學檢測，隨后處死模型分別取兩肺中帶上、中、下野6處標本，分別進行HE染色光鏡、電鏡和局部肺組織TNF-a、TGF-β1的檢測。實驗組各時間點若有模型死亡，及時添加新個體進行補充。 結果：⑴實驗組兩只分別于照射后第2、8周死亡，實驗周期內(nèi)總死亡率3.3%。⑵實驗組所有兔受照射肺均產(chǎn)生了RILI，早期以急性炎癥反應為主，晚期以進行性肺纖維化為特征。⑶實驗組受照射1小時后局部肺組織TNF-α表達、48小時后TGF-β1表達與對照組差異有統(tǒng)計學意義（P值均＜0.05）。⑷光鏡下，實驗組受照射1小時后肺泡壁厚度、肺間質(zhì)面積密度、24小時后間質(zhì)內(nèi)纖維母細胞和纖維細胞數(shù)量與對照組差異均有統(tǒng)計學意義（P值均＜0.05），并分別與照射后的時間直線相關（r=0.82086、0.87181、0.68230，P值均0.05）。⑸電鏡下，實驗組各時間點之間膠原纖維相對含量差異有統(tǒng)計學意義（F=100.31，P=0.000），對照組各時間點之間的差異無統(tǒng)計學意義（F=1.00，P=0.450）。實驗組受照射48小時后肺內(nèi)膠原纖維相對含量與對照組差異有統(tǒng)計學意義（P值均＜0.05），并與照射后時間直線相關（r=0.99318，P=0.0000）。 結論：RILI兔階梯模型具有良好的可靠性、穩(wěn)定性以及RILI發(fā)生發(fā)展的階梯性，較好地模擬了RILI的發(fā)生、發(fā)展的演變過程。細胞因子等對RILI的診斷有一定的參考意義，但不能作為診斷或預測的依據(jù)。 第三部分放射性肺損傷兔階梯模型功能成像技術研究 目的：探討健康新西蘭大白兔的CT灌注成像（CTPI）技術參數(shù)及其定量分析的可行性。 方法：健康新西蘭大白兔36只假照射組（雌雄各18只），均由同一麻醉師使用同樣的混合法麻醉技術，即先肌注地西泮（用量為0.8~1.0mL/kg），后肌注速眠新II號（用量為0.4~0.5mL/kg），然后經(jīng)自制中型動物醫(yī)學成像掃描床固定后，分別于假照射后照射后第1、6、12、24、48、72小時及第1、2、4、8、16、24周進行階梯性常規(guī)CT掃描及CT灌注成像（CTPI）。CTPI使用設備為西門子新雙源CT機（FLASH），采用全肺4D容積動態(tài)掃描技術。掃描參數(shù)：管電壓100kv，管電流自動調(diào)節(jié)；4D1.5s模式；非離子對比劑規(guī)格為300mg I/mL，總量5mL，注射流速0.8mL/s。CTPI時采用專用動物呼吸機進行呼吸暫停15s。 結果:36只大白兔均能獲得層次豐富、結構清晰的CTPI圖像，肺野內(nèi)任意取不同大小的感興趣區(qū)（ROI），均能獲得重復性好的灌注值；正常兔肺的rBF、rBV及rPS平均值分別為123.8±25.9mL/100mL/min、13.04±2.07mL/100mL、8.97±2.14mL/100mL/min；肺部各灌注參數(shù)及密度值（HU）在雌雄性別、左右部位等方面的差異無明顯統(tǒng)計學意義（P0.05）；上、下肺野ROI的rBF、rBV值的差異有顯著統(tǒng)計學意義（P0.05）。假照射后不同時間點的各對應灌注值重復性佳，各時間點CTPI參數(shù)差異無明顯統(tǒng)計學意義（P0.05）。 結論:正常兔全肺CTPI各參數(shù)值能夠進行定量測量與分析，且重復性好，，與人類全肺具有相似的變化規(guī)律。 第四部分雙源CT灌注成像早期診斷放射性肺損傷的實驗研究 目的：利用全肺雙源CT灌注成像（CTPI）技術研究放射性肺損傷（RILI）兔階梯模型的血流動力學變化規(guī)律，探索其發(fā)病進程中的病理基礎及其早期診斷RILI的價值。 方法：健康新西蘭大白兔72只，利用隨機數(shù)字表分為兩組：實驗組36只行25Gy單側全肺單次照射，對照組36只為空白對照組，行單側全肺假照射；兩組按照射后1、6、12、24、48、72h和1、2、4、8、16、24周各分為12個亞組。每只兔于照射前和照射后所處亞組時間點做常規(guī)CT和CTPI，后取肺組織行光鏡、電鏡觀察，將同期CTPI表現(xiàn)、病理變化及HRCT征象作對照分析。實驗組與對照組CTPI參數(shù)比較采用t檢驗，CTPI參數(shù)與病理觀察值的相關性采用兩變量直線相關分析，CTPI與常規(guī)CT對RILI檢出率比較采用卡方檢驗。 結果：⑴對照組肺CTPI參數(shù)在各時間點上保持在相對穩(wěn)定的水平。實驗組照射后肺實質(zhì)血流量（rBF）、血容量（rBV）和毛細血管通透性（rPS）在多數(shù)時間點上（6、12、72h及1、2、8、16、24周）與照射前差異有顯著統(tǒng)計學意義（t=2.90～6.37，P＜0.05），呈“先降—后升—再降”的規(guī)律：1～12h先短暫的降低，后快速升高并顯著高于對照組，于72h至2周分別達高峰，隨后下降，并逐步低于對照組，至24周達最低值。⑵實驗組受照射肺病理變化以毛細血管內(nèi)皮細胞、基底膜和肺泡上皮細胞損傷為主，并隨時間呈現(xiàn)一定規(guī)律性。實驗組照射后肺rBF、rBV與病理改變有顯著相關性（r=0.74、0.83，均有P＜0.05），rPS與毛細血管外紅細胞數(shù)、毛細血管基底膜破壞之間有顯著依存關系（r=0.87、0.88，均有P＜0.05）。⑶在所有時間點上，CTPI對RILI的檢出率均高于HRCT，兩者差異有統(tǒng)計學意義（χ2=4.37，P=0.036）。根據(jù)ROC曲線，兩者診斷RILI的敏感度、特異度分別達92.3%、90.0%與69.2%、90.0%（Z＝13.06，P0.05），CTPI的診斷效能明顯優(yōu)于常規(guī)CT，尤其是在RILI模型的早期階段（放療后的前4周）。 結論：CTPI參數(shù)初步揭示了RILI過程中的血流動力學演變規(guī)律，并間接反映以肺毛細血管通透性為主要變化的病理生理狀態(tài)；RILI的CTPI異常在時間上先于常規(guī)CT，有望成為早期檢測與早期診斷RILI的有力手段。
[Abstract]:Part I: dual source CT lung perfusion imaging and its clinical significance in radiation-induced lung injury
Objective: in the case of radiation-induced lung injury (RILI) after chest radiotherapy, the conventional image morphologic changes are late, and the clinical difficulty is difficult to diagnose early. Can the chest functional imaging reflect the function changes of RILI more early than the traditional image? This study applies the dual source CT pulmonary perfusion imaging (CTperfusion imagin). The feasibility of G, CTPI and its clinical value in early diagnosis of RILI.
Methods: 20 patients, aged 47-76 years (male and female, 10 cases), were selected from the clinical screening of pulmonary embolism with 4D-CT enhanced examination but negative imaging diagnosis and the final clinical exclusion of lung disease. The experimental group was 48 cases of upper esophageal or thymic tumor (total radiation dose of 60Gy). 43-70 years of age (27 males and 21 females). CTPI examination before and after radiotherapy (30Gy), and simultaneous detection of tumor necrosis factor (TNF- alpha) and transforming growth factor (TGF- beta 1) in peripheral blood, serum cytokine, routine CT expression and CTPI perfusion value [relative blood flow (rrBF)) of RILI (group A) and RILI (B group) patients. For the change of blood volume (rrBV) and relative capillary permeability (rrPS), the difference of serum cytokine and CTPI perfusion value between two groups was compared by random area group design t test. The difference between the routine CT and CTPI was compared with the routine CT and CTPI. The lung 4D volume scan technique of the new SIEMENS dual source CT machine (FLASH) was used as the CTP imaging method first. Conventional high-resolution CT plain scan (HRCT) was performed and perfusion imaging was performed later.
Results: (1) all the 20 patients in the control group were able to obtain a rich, clear structure CTP image, ROI in the lung field, and can obtain a good repetitive perfusion value. The average value of rBF, rBV and rPS in normal adult lung was 149.3 + 18.3mL/ 100mL/min, 14.86 + 2.65mL/100mL, 9.54 + 2.91mL/100mL/min, lung, lung, and lung. There was no significant difference between the sex and sex of the Department of perfusion and density (HU), and the difference of the left and right parts of the two sexes (P0.05); the rBF of ROI in the lower lung field, rBV value had significant difference (P0.05), there was no significant difference between the upper and middle and lung fields and the middle and lower lung fields (P0.05). (2) 48 patients had RILl (A group).A group peripheral blood TNF- alpha and TGF- beta 1 before and after radiotherapy. There was no statistical significance (all P0.05). There was no significant difference between groups of peripheral blood TNF- A and TGF- beta 1 in group A and B two with total 1/2 dose (P0.05), but there were 2 positive signs in the conventional CT image of A group and rrBF in the lung tissue of the lung tissue in the.A group. The difference was statistically significant (all P0.05), and there was no significant change in rrPS (P0.05). After A, B two groups rrBF, rrBV, rrPS were statistically significant (P0.05). According to the ROC curve, rrPs=1.22 as the threshold, the sensitivity of the RILl was diagnosed, the specificity was 88.9%, 90%, respectively, 11.1%, 90% (chi square). (x, 90%) and (3) control group and (3) control group and (3) control group and There was no significant difference in the corresponding perfusion values between the experimental group before and after radiotherapy (P0.05).
Conclusion: (1) the dual source CTPI technique can be used to study the perfusion imaging of lung tissue and can quantitatively analyze the hemodynamic parameters of lung tissue (rBF, rBV, rPS, etc.). (2) the change of TNF- alpha and TGF- beta 1 in peripheral blood is uncertain for the early detection of RILI in patients with tumor radiotherapy. (3) CTPI can reflect the changes in hemodynamics of lung tissue after radiotherapy and can be reversed in early stage. Abnormal perfusion of radiation field in patients with RILI may be an effective tool for early detection of RILI.
The second part is the preparation and identification of rabbit ladder model for radiation lung injury.
Preparation of a rabbit ladder model for radiation lung injury (RILI)
Objective: it is necessary to establish an animal model suitable for dynamic observation and study of human radionuclide injury (RILI), which is difficult to accurately grasp in clinical and difficult to carry out biochemical, imaging, histopathological and other repetitive studies. The purpose of this study is to explore the preparation method of the rabbit ladder model of radionuclide injury (RILI).
Methods: 54 healthy New Zealand white rabbits were randomly divided into group A, group B and group C, 18 in each group. The same anesthetic technique was used by the same anesthesiologist in the three groups, that is, the first anaesthediazepam (0.8~1.0mL/kg) was injected first, and then the new II number (0.4~0.5mL/kg) was injected after the muscle injection (the dosage was 0.4~0.5mL/kg), and then fixed by the self-made medium size animal medical imaging scanning bed. High energy X-ray single side whole lung irradiation, irradiation dose of 35Gy, 25Gy and 15Gy respectively, were observed on the ladder routine CT after 1,2,3,4,5,6,8,12,16,20,24 week respectively. The safety and effectiveness of mixed anesthesia were observed, and the time of CT positive expression in each model group and the total mortality of each model were compared.
Results: (1) the anesthetic effect of the three groups was significant, the time of unconscious anesthesia was 30-40 minutes, and the death rate of anesthesia was zero. 2. A, B, C three models, the peak time points of the exudative glass shadow of the three groups were 2 weeks, 4 weeks, 16 weeks respectively, and all were further confirmed at the subsequent step time point, that is, the production of RILI; in the model The number of deaths was 4, 1 and 1, respectively, with a mortality rate of 22.2%, 5.6%, 5.6%.
Conclusion: the mixed method of anaesthesia has the advantages of high safety, good reproducibility, strong controllability and easy operation. The.B group (25Gy) has the advantages of moderate mold forming time, low mortality and staircase symmetry, which is beneficial to further RILI ladder analysis. It is the first choice method.
Two, identification of the ladder model of radionuclide injury
Objective: the development of radiation-induced lung injury (RILI) is more complicated, and there is no clear demarcation in each period of RILI. Therefore, it is of important clinical significance for the dynamic observation and identification of RILI animal model. Therefore, this study aims to explore the dynamic serology and histopathological identification of the RILI rabbit staircase model in order to determine the ladder. The occurrence and evolution of the model.
Methods: in the same way, 60 healthy New Zealand white rabbits were created by high energy X-ray single lung single irradiation, and the experimental group was set up as the experimental group. At the same time, 36 rabbits were randomly irradiated with the same batch of white rabbits, set up as the control group, and divided into 12 subgroups according to the time point of the following irradiation, and each subcomponent of the experiment and the control group was divided into 12 subgroups. 5, 3, respectively, after exposure to the heart after exposure to the chest 1,6,12,24,48,72 hours and 1,2,4,8,16,24 weeks after exposure to the heart to extract 4-8mL whole blood for serological examination. Then the model was executed in two lungs, middle and lower field 6 specimens, respectively, HE staining light microscopy, electron microscopy and local lung tissue TNF-a, TGF- beta 1 detection. If there are model deaths at each time point, new individuals will be added in time.
Results: (1) the experimental group died after 2,8 week after irradiation, and the total mortality was 3.3%. in the experimental period. (2) all the rabbits in the experimental group were exposed to RILI, early acute inflammatory reaction and progressive pulmonary fibrosis in the early stage. (3) the expression of TNF- alpha in the local lung tissue in the experimental group after 1 hours of irradiation, and the TGF- beta 1 after 48 hours. The difference between the control group and the control group was statistically significant (P value < 0.05). 4. Under the light microscope, the thickness of the alveolar wall and the density of the interstitial area of the lung in the experimental group were 1 hours after irradiation, and the number of fibroblast and fibroblast in the interstitial tissue after 24 hours was statistically significant (P < 0.05), and was linearly related to the time after irradiation (r=0.82086 0.87181,0.68230, P values were all 0.05). Under the electron microscope, the relative content of collagen fiber in the experimental group was statistically significant (F=100.31, P=0.000), and there was no statistical difference between the control group (F=1.00, P=0.450). The relative content of collagen fiber in the experimental group was statistically different from that of the control group after 48 hours of irradiation. Significance (P < 0.05), and correlated linearly with the time after irradiation (r=0.99318, P=0.0000).
Conclusion: the RILI rabbit staircase model has good reliability, stability and the staircase of RILI development. It can simulate the occurrence of RILI and the evolution process. The cytokine has some reference significance for the diagnosis of RILI, but it can not be used as a basis for diagnosis or prediction.
The third part is the functional imaging technology of rabbit model with radiation lung injury.
Objective: To explore the feasibility of quantitative analysis of CT perfusion imaging (CTPI) parameters in healthy New Zealand rabbits.
Methods: 36 healthy New Zealand white rabbits (18 males and males each) were used by the same anesthesiologist, the same anaesthetized technique was used by the same anesthesiologist, that is, first intramuscular injection of diazepam (the amount of 0.8~1.0mL/kg), and then the post muscle anaesthetized new II (0.4~0.5mL/kg). After 1,6,12,24,48,72 hours and 1,2,4,8,16,24 weeks, the ladder routine CT scan and CT perfusion imaging (CTPI).CTPI use equipment are SIEMENS's new dual source CT (FLASH), and the whole lung 4D volume dynamic scanning technique is used. The scanning parameters: the tube voltage 100kV, the tube current auto tuning, 4D1.5s mode, and the non ion contrast agent specification for 300mg I/m L, the total amount of 5mL, the injection rate of 0.8mL/s.CTPI when using a special animal ventilator for apnea 15s.
Results: all the 36 rabbits were able to obtain a rich and clear CTPI image with a distinct size of ROI in the lung field. The average value of rBF, rBV and rPS in normal rabbit lung was 123.8 + 25.9mL/100mL/min, 13.04 + 2.07mL/100mL, 8.97 + 2.14mL/100mL/min, and pulmonary perfusion parameters. And the density value (HU) had no significant statistical significance (P0.05) in gender, left and right position (P0.05), and the difference of rBV value of ROI in the lower lung field was statistically significant (P0.05). The corresponding perfusion values at different time points after sham irradiation were good, and there was no significant statistical significance (P0.05) for the difference of CTPI parameters at each time point.
Conclusion: the parameters of the whole lung CTPI can be quantitatively measured and analyzed, and the repeatability is good, which is similar to that of the whole lung.
The fourth part is an experimental study of early diagnosis of radiation-induced lung injury by dual source CT perfusion imaging.
Objective: To study the hemodynamic changes in the rabbit model of radionuclide injury (RILI) by using the whole lung dual source CT perfusion imaging (CTPI) technique, and to explore the pathological basis and the value of early diagnosis of RILI in the course of the disease.
Methods: 72 healthy New Zealand white rabbits were divided into two groups by random numbers: 36 rats in the experimental group were irradiated with 25Gy unilateral whole lung, and 36 in the control group were blank control group, and the two groups were divided into 12 subgroups according to 1,6,12,24,48,72h and 1,2,4,8,16,24 weeks after radiation. CT and CTPI were performed at the time point of the group, then the lung tissue was taken by light microscopy and electron microscopy, and the CTPI expression, pathological changes and HRCT signs were compared. The experimental group and the control group were compared with the CTPI parameters by t test. The correlation between the CTPI parameters and the pathological observation values was analyzed by the two variable linear phase correlation analysis. CTPI and conventional CT were used to compare the detection rate of RILI. Chi square test.
Results: (1) the pulmonary CTPI parameters in the control group remained relatively stable at all time points. The pulmonary parenchyma blood flow (rBF), blood volume (rBV) and capillary permeability (rPS) in the experimental group were statistically significant (t=2.90 to 6.37, P < 0.05) at most time points (t=2.90 to 6.37, P < 0.05), showing a "first drop". The law of post rise and second descent: 1 ~ 12h was reduced first briefly, then increased rapidly and was significantly higher than that of the control group, reaching the peak in the 72h to 2 weeks, and then decreasing, and gradually decreasing to the control group, and reaching the lowest value at 24 weeks. 2. The experimental group was subject to the pathological changes of the capillary endothelium, basal membrane and alveolar epithelial cells in the experimental group. The time showed a certain regularity. There was a significant correlation between the rBF and rBV of the lung in the experimental group and the pathological changes (r=0.74,0.83, P < 0.05). There was a significant difference between the number of rPS and the extra capillary red blood cells and the destruction of the capillary basement membrane.
【學位授予單位】：蘇州大學
【學位級別】：博士
【學位授予年份】：2014
【分類號】：R730.44

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