ABSTRACT
Objective: To study the impact of vascular injury on neointimal hyperplasia and the expressions of nuclear transcription factor-κb (NF-κb), tissue factor (TF), endothelin-1 (ET-1) and matrix metalloproteinase-3 (MMP-3) in experimental rabbit model. Methods:A total of 32 male New Zealand big-eared white rabbits were used to establish vascular injury model by femoral artery puncture, balloon was sent to abdominal aorta via the wire followed by balloon dilatation to strain abdominal aorta. Blood sample was taken from femoral artery sheath 1 minute after operation, and the rabbits were killed at 4 weeks after operation, meanwhile blood sample was taken from the heart. Injured arteries were isolated, ifxed and embedded; slices were stained by HE, basic fuchsine and NF-κb immunohistochemical methods for light microscope observation; slices were also stained by lead and uranium for transmission electron microscope observation. Neointimal thickness was measured by computer analysis, vascular injury integral and NF-κb positive cell rate were determined, blood levels of TF, ET-1 and MMP-3 were examined by ELISA. The relationship between vascular injury integral and the contents of TF, ET-1, MMP-3 and NF-κb positive cell rate were analyzed by SPSS statistical software. Results: The optimal iftting curve between vascular injury integral and neointimal thickness was S-shaped cubic curve. NF-κb was mainly expressed in neointima, vascular injury integral was positively related to NF-κb positive cell percentage, Pearson correlation coeffcient was 0.916,P Conclusion: Vascular injury may activate NF-κb pathway, promote ET-1 and MMP-3 expression, therefore accelerating neointimal hyperplasia, leading negative vascular remodeling, TF was an initiating factor for neointimal hyperplasia. Internal elastic lamina was the key structure reflecting vascular injury, it is the only barrier hindering neointimal hyperplasia in experimental rabbit model.
ABSTRACT
BACKGROUND: Until now, the definite source of respiratory rhythm generation and the ontogenic mechanism are still in controversy. Previous our investigating indicated that respiration would stop due to the gentle press on the hypoglossal root under the surface of ventral medulla of rabbit. OBJECTIVE: To observe the influence of mechanical lesion in medial re gion of nucleus retrofacialis on respiratory rhythm of a living rabbit model.DESIGN: Randomized controlled study.SETTING: At the Physiology Teaching Room of Kunming Medical College.MATERIALS: This study was carried out at the Physiology Teaching Room of Kunming Medical College from February 2002 to December 2002. Totally 54 healthy rabbits were randomly selected, amongst which 22 rabbits were submitted to the mechanical damage of the medial region of bilateral nucleus retrofacialis by the dorsal processes, and 18 received the same damage by the ventral process, 14 rabbits used for observing the changes of blood pressure andheart rate due to the mechanical damage.METHODS: The ventral and dorsal medullar of rabbits were exposed and the bilateral vagotomy at the cervical level were cut. Discharge of the phrenic nerve was used as the respiratory index. Stainless pipe of 0. 8 mm or 0.4 mm diameter was used to make mechanical damage at the medial region in order to investigate the changes of respiration. Fourteen rabbits were selected and submitted to the bilateral mechanical damage, the changes of blood pressure and heart rate were observed at post-traumatic 1 -3 minutes.MAIN OUTCOME MEASURES: ① The changes of respiratory rhythm induced by the mechanical damage of the medial region of bilateral nucleus retrofacialis. ② The number of phrenic nerve discharge and respiratory frequency. ③ The changes of blood pressure and heart rate at post-lesion 1-3minutes.RESULTS: Data of 54 rabbits were analyzed. ① Irreversible disappearance of respiratory rhythm was found in 12 out of 18 rabbits (the positive rate was 67% ) due to the mechanical damage by the ventral processes, comparing to 3 / 14 (14%) by the dorsal process. ② Rhythmic discharge of phrenic nerve became scarce and irregular in all rabbits who has irreversible disappearance of respiratory rhythm, the inspiratory and expiratory discharging phase were significantly prolonged, moreover respiratory rhythm would disappear if expiratory phase was extremely extended, respiration stopped at expiratory phase. ③ When the medial region of bilateral nucleus retrofacialis was partially destroyed, the still existed respiration of 27 rabbits was found immediately inhibited, phrenic nerve discharge frequency obviously decreased [ (43.5 ± 6.4)%, P ＜ 0. 001 ], and its discharge number was significantly decreased [ (42.0 ± 3.7 )%, P ＜ 0. 001 ], moreover the inspiratory and expiratory discharging phase were found obviously extended, with expiratory phase was in particular. ④ From the results of histological examination on the above mechanical lesion. Respiration stop or obvious attenuation was found mostly due to the damage at the medial region of nucleus retrofacialis.⑤ The blood pressure and heart rate changed slightly by 5% -7% at post-traumatic 1 -3 minutes, there was not significantly different from the normal value ( P ＞ 0. 05).CONCLUSION: The medial region of nucleus retrofacialis might be the main source of respiratory rhythm generation, and the related neuron within it would be the important component involving in the generation of respiratory rhythm.