| Pulmonary emphysema is a common disease severely threatening human health in the world. There is no effective drug to prevent the progressive loss of lung parenchyma at present. According to the available pathogenesy of emophysema, destruction of the alveolar walls, one of the pathologic changes in pulmonary emphysema, had been considered irreversible. Have been studying and researching on LVRS and the Bronchial lumen blocking up for many years, Li Baoping professer had proposed a new pathogenesy of emphysema:"The damage to the pulmonary capillary plays an important role in the development of pulmonary emphysema. The damages of pulmonary alveolus capillary cause the loss of pulmonary blood flow and lead to ventilates/perfusion shunted, and the lungs reduced the gas diffusion area to compensate for the shunt of ventilates/perfusion by enlarging alveolus. Finally, these lead to the appearance of pulmonary emphysema".According to the hypothesis, the pathology of emphysema could be restored by promoting the regeneration of pulmonary capillary .Study objectives: This research will verify our hypothesis by promoting the pulmonary capillary of emphysema rats induced by cigarette smoking plus elastase with using bFGF, VEGF and MSCs. The study will improve the pathogenesy of emphysema and supply a new approach and theory to the treatment of emphysema.Methods: In the first part, sixteen 8 week old Wister rats weighing 180 to 200g were classified at random into the following 2 groups: Model group(A, n=8) and Control group(B, n=8). A group rats were exposed to tobacco smoke and received a single intratracheally instillation of porcine pancreatic elastase (PPE) (2U/g). Rats of B group were intratracheally injected Sodium Chloride. 4 weeks later, we measured the arterial blood gas and detected alveoli morphology and the pulmonary capillary to appraise the models.In the second part,forty-eight 8 week old Wister rats weighing 180 to 200g were distributed randomly into the following 6 groups: bFGF group(A, n=8),VEGF group(B, n=8),MSCs group(C, n=8),MSCs +VEGF group(D, n=8),Control group(E, n=8) and Normal group(F, n=8). A,B,C,D,E group rats were exposed to tobacco smoke and received a single intratracheally instillation of porcine pancreatic elastase (PPE). Rats of F group were intratracheally injected Sodium Chloride. 3 months later, the emphysema models were done. Then A,B group rats were intratracheally injected bFGF(400U) and VEGF(2ug) once a week for three times in all. C group rats were injected MSCs labeled with BrdU into tail vein. D group rats were injected MSCs labeled with BrdU(one time) into tail vein and intratracheally injected VEGF(2ug) (three times). E,F group rats were intratracheally injected Sodium Chloride. 4 weeks after treatment, we weighed the rats, measured arterial blood gas, detected alveoli morphology and detect the changes of pulmonary capillary with immunohistochemistry method.Results: 1. 3months after smoke exposure and PPE intratracheal administration (50U/100g), emphysematous pathological changes existed. The pulmonary capillary was significantly decreased (P<0.05).2. bFGF,VEGF and MSCs could increase the generation of pulmonary capillary. Mean Alveoli Number (MAN) was significantly increased(p<0.05). Mean Linear intercept (MLI) and Mean Alveoli Area (MAA) was significantly reduced in contrast to the control group(p<0.05) . The number of pulmonary capillary of the bFGF, VEGF and MSCs group was significantly increased (p<0.05). The emphysematous pathology was improved. Arterial blood gas analysis showed that VEGF group compared with the control group significant (P<0.05), and the rest are not statistically significant (P>0.05).Conclusion: 1. bFGF,VEGF and MSCs improved the pathology of pulmonary emphysema.2. The possible mechanism of bFGF,VEGF and MSCs of recovering the pulmonary emphysema is:①t he proliferation of pulmonary capillary and enlargement of pulmonary artery improved the blood flow in the lung, leading to an improvement in the ventilation/perfusion shunt and in the gas exchange ability of the lung, the lung then can adjust the pulmonary alveolus size and volume through self-compensation to smaller state.②The increased blood flow of emphysema improved self-repairing capability of lungs and the alveolar septum was increased by typeⅡpenumonocyte self-replication and differentiating into the typeⅠp enumonocyte.3,It verified the hypothesis in some degree,"The damage to the pulmonary capillary plays an important role in the development of pulmonary emphysema."... |
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