Roles of mitochondrial pathway-mediated apoptosis in intracranial aneurysm initiation in rabbits / 中国脑血管病杂志

ABSTRACT

Objective Toinvestigatethemolecularmechanismsofmitochondrialpathway-mediated apoptosisinintracranialaneurysminitiationinrabbits.Methods FifteenNewZealandwhiterabbitswere divided into 3 groups using the computer random method. After using bilateral carotid artery ligation for modeling basilar artery aneurysm,they were divided into a 2-day group (n=3),a 7-day group (n=6)(3 of them were used for real-time quantitative polymerase chain reaction [PCR]analysis),and a sham operation group (n=6)(3 of them were used for real-time quantitative PCR analysis). The tissue of apex of basilar artery was harvested and the histopathological changes in the vascular wall were observed. TUNEL staining was used to detect apoptotic cells and immunohistochemical staining,and quantitative analysis was used to analyze inflammatory cell distribution. Real-time quantitative PCR was used to detect the expression of apoptosis-related protein mRNA. Results (1 )After modeling,the apoptotic cells were found at the apex of basilar artery in rabbits (the site of internal elastic layer lesion )of the 2-day group and 7-day group. In the 2-day group after operation,the numbers of apoptotic cells (4. 02 ± 0. 21)were significantly higher than those of the basilar artery trunk (0. 40 ± 0. 13),the left posterior cerebral artery (0. 41 ± 0.22),and the right posterior cerebral artery (0. 29 ± 0. 11). The differences were statistically significant (P<0. 05). After modeling,the numbers of apoptotic cells (5. 01 ± 0. 29)of the 7-day group were significantly higher than those of the basilar artery trunk (0. 49 ± 0. 21),the left posterior cerebral artery (0. 31 ± 0. 12),and the right posterior cerebral artery (0. 41 ± 0. 19)(P<0. 05). The internal elastic layer lesions and apoptotic cells were not observed in the rabbits of the sham operation group. (2)After modeling, the expression levels of caspase 9 (1. 97 ± 0. 23)and caspase-3 mRNA (2. 31 ± 0. 40)at the apex of basilar artery in rabbits of the 7-day group were increased significantly compared with that of the sham group (P<0.01).Conclusion Apoptosisisinvolvedintheearlyprocessofaneurysmsinsimple hemodynamics-induced basilar terminus aneurysm formation. Its molecular mechanisms are activated by Bcl-2-mediated mitochondrial pathway through caspase-9.