| Objective Cerebral vasospasm (CVS) following subarachnoid hemorrhage (SAH) is a major cause of high mortality and morbidity for those experiencing the rupture of intracranial aneurysm, and it often induces ischemic neurological deficits. But its true mechanism and secondary impairment still remain unclear, and there is no very effective method to prevent and treat CVS. Lots of clinical and experimental studies have shown that Endothelin-l(ET-l), peptide of 21 amino acids, is a key CVS-inducing factor. So more and more studies have focused on the inhibition of ET-1 biological synthesis and its biological activity. In the present study we assessed the anti-CVS effect of [D-Val22] big ET-l(16-38), an endothelin converting enzyme that inhibit the convert of inactive big ET-1 to active ET-1, in rabbit CVS model after we observed the changes of basilar arteries' diameters through cerebral angiography, performed immunohistochemical staining of basilar arteries' endomelial cells(EC) and smooth muscle cells(SMC), and studied ultrastructural changes of basilar arteries under transmission electron6microscope(TEM).Methods CVS model was developed by injecting arterial blood twice through the citerna magna 48 hours apart.(l) 36 rabbits were equally assigned to six groups as follows: groupl, group2, groupS, group 4, groupS, and group6. In group 1, rabbits wre injected twice with 2.5 ml of phisiological saline 2 days apart; In group2 rabbits, SAH was produced by injecting 2.5ml of autogenous arterial blood into subarachnoid space through cistema magna two times; GroupS animals were given twice 2.5ml of blood and immediate 0.5ml saline containing 10~2 u mol of [D-Val22] big ET-1 (16-38) via cisterna magna; Group4 rabbits were injected 2.5ml of blood through the cistema magna and immediate 0.5ml saline containing 10~2nmol of ET-1 (16-3 8) intravenously, which was repeated 2 days later; In group5 rabbits, 2.5ml of blood was administered via the cisterna magna and 24 hours later, 0.5ml saline containing 10"2umol of [D-Val22] big ET-l(16-38) was given in the same way, then 48 hours after SAH, the above procedure was performed again; In group6, 24 hours after SAH was induced, the rabbits received 0.5ml saline containing 10"2umol of big ET-l(16-38) intravenously and 48 hours after SAH the same process was repeated. (2)A11 rabbits underwent cerebral angiography before and on SAH Day?. (3)All animals were killed using perfusion-fixation on Day? . Then the basilar arteries and some brain tissue were removed for ultrastructural and immunohistochemical studies. All data hi this study were expressed as the mean ?the standard deviation and the Student t-test was used to compare the difference between the groups.Results (1) In groupl rabbits, angiography showed the basilar arteries'diameters decreased from 0.70 ?.1 Omm to 0.69?0.086 mm; In group2 rabbits, from 0.70 +0.079mm to 0.47?0.075 mm; In group3, from 0.69 ?0.092mmto0.615 ?0.07mm; In group4, from 0.67 ?0.076mm to 0.605 ?0.063mm; In groupS, from 0.70 ?0.086mm to 0.63 ?0.069mm; In group6, from 0.68 ?0.073mm to 0.61 ?.088mm. (2)m group 1,3,4,5 and 6, the differences were not significant between two angiographies(p>0.05), while in group2, there was significant difference(p<0.05). In group3,4,5 and 6, the Day? angiography demonstrated the basilar arteries' diameters increased significantly(p<0.05), compared with group2; but not markedly compared with groupl(p>0.05). (3)The immunohistochemical study on SAH Day? found that in groupl, the basilar arteries showed scattered irregular positive staining , but SMC revealed no positive staining; in group2, severe positive staining was found in EC, SMC and adventitia, especially more in EC; in group3,4,5 and 6, EC, SMC and adventitia showed slightly immunohistochemical staining. But there was no positive staining in brain cells adjacent to basilar artery. (4)TEM displayed normal morphology of EC, its conjunction, SMC and intimal elastic lamina(IEL) in groupl rabbits; while in group2, noted pothological changes were obs...
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