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An Experimental Study Of Lung Cell Proliferation And Apoptosis At Pre And Post-operative Of Lung Volume Reduction In Rabbits

Posted on:2002-07-07Degree:MasterType:Thesis
Country:ChinaCandidate:H XuFull Text:PDF
GTID:2144360032952453Subject:Surgery
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Objective Pulmonary emphysema is a kind of chronic obstructive pectoral disease with a high incidence and mortality. Up to now, there is still no effective and curative treatment for the disease, particularly at its advanced stage. Although lung volume reduction surgery (LVRS) has recent years achieved the remarkable outcome clinically, however, few studies of physiopathologic changes related to the surgical procedure are reported. The main goals of this study are: to compare the affection of carbon monoxide diffusing capacity (DLCO) with the membrane diffusing capacity (Dm) and pulmonary capillary blood volume (Vc) pre and post-operatively; to observe the variation of lung cell proliferation and apoptosis before and after LVRS and to sight intothe relationship between the lung cell proliferation and apoptosis during chronic anoxia.Methods (1) Induction of emphysema: 30 New Zealand White rabbits inhaled aerosolizing 5% papain (50 ml) each time approximately four hours, once a week, totally for three dosages. One month later after the last inhalation, the pulmonary emphysema animal model was conformed to be available to perform the LVRS by x-ray film, CT scanning and pathological finding. (2) LVRS: The 30 emphysematous rabbits induced by papain were performed unilateral LVRS through right thoracotomy. The right upper and middle lobes were excised using a linear thoracoscopic stapler buttressed with bovine pericardial strips. Target quantity of lung tissue removed was 3 gm. (3) Arterial blood gas analysis, DL, Dm and Vc were measured at baseline before induction of emphysema and LVRS immediately preoperatively, and at 4 weeks after the operation. (4) Lung cell proliferation and apoptosis detection: the animals were sacrified at four weeks after LVRS and lungs were removed en bloc. The lung cell proliferation and apoptosis were determined quantitatively and qualitatively by immunohistochemical and terminal deoxynucleotidyltransferase mediated dUTP nick end labeling (TUNEL) techniques. Results All rabbits that were successfully induced with emphysema survived after LVRS. (1) Histological examination conformed presence of severe diffuse emphysema with pathomorphological features in each animal at necropsy. It was characterized by sparse pulmonary tissue, narrowed alveolar septum and pressed inner capillaries. Even part of alveolus septa were destructed or disappeared, and some of alveoli were formed a big round hydatid with dilated alveolus tubes. (2) The proportion of actual measured DL values to assessed DL values, Dm Vc and Pa02 before and after LVRS were (63?)% and (77?)%, (67?)% and (71?)%, (71?)% and (83?)%, (.78?.2)mmHg and (92.8?.4)mmHg respectively. There are significant differences of values between pre and post-operation in the all groups except Group Dm. (3) TUNEL examination showed scattered apoptosis cells with brown cell nucleus and concentrated or crescent shaped nucleus chromatin to be observed under microscopy. Proliferated cells emerged as Ki-67 nucleus positive reaction. The number of apoptosis cells and Ki-67 nucleus positive cells were (5.9?.8)% and (1.7?.8)% before LVRS, and (3.6?.2)% and (2.7?.9)% after LVRS respectively.Conclusions (1) An experimental animal pulmonary emphysema model was successfully induced by aerosolizing papain in rabbits with typical, pathomorphological features of pulmonary emphysema. It was believed to be an ideal and reliable animal model for study of the emphysema. (2) The results showed that the lung diffusing function of the rabbit was severe impaired relating to the decreasing of membrane diffusing capacity (Dm) and blood volum of pulmonary capillary (Vc). The diffusing function, PaO2 and anoxia were significantly improved after LVRS closely relating to the increased Vc other than Dm. (3) The balance between proliferation and apoptosis of the lung cell was destructed resulting in the lung cell apoptosis increasing due to chronic anoxia before LVRS. The lung cell apoptosis and proliferation gradually reached their norm...
Keywords/Search Tags:pulmonary emphysema, lung volume reduction surgery, apoptosis, proliferation.
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