The Screening on the Pathogenetic Genes and Study on Endovascular Intervention of Intracranial Aneurysms
|Keywords||Intracranial aneurysm Array C0L3A1 gene Single neucleotide polymormism Guglielmi detachable coils Neuroform stents|
OBJECTIVE: This research includes three parts. In the first part of the research, whole Genome BeadChip was used to detect the differential expression genes in intracranial aneurysms and thus shed light on the pathogenesis of intracranial aneurysms at genetical level. The second part of the research was to explore the genetic polymorphism of chainα1 of collagen proteinⅢ(COL3A1) and its relationship with the development of intracranial aneurysms using polymerase chain reaction -restricted fragment length polymophishm (PCR-RFLP). The third part of the research was a clinical study for further evaluating the effectiveness and risks of application of electrolyze detachable coil in the treatment of intracranial anerysms.METHOD: Part I: Collect 3 intracranial aneurysm cases from July 2003 to May 2005 at Shandong Provincial Hospital neurosurgery. Operative clipping of aneurysm was done, and the removed aneurysm was thrown into liquid nitrogen to preserve immediately. 3 samples of arteria temporalis superficialis from patients with cerebral trauma were taken as controls The two groups were all 2 men and 1 woman, their ages were 40 to 60, and they did not have any special management before operation. Extracting total RNA, the cleansing of total RNA, extraorgan reverse transcription becomes cDNA, the cleansing of cDNA, extraorgan transcription synthesizes cRNA, the cleansing of cRNA, the allomixis of gene array, elution, and tinction in order are undertaken line scanning and analysis of data with BeadSation. And chose the point of significant difference (numerus p is 0.01 ) between selective gene intensity and background signal. The experimental data deploys normalize disposal for correcting small difference systematic error in different sample. It selects intracranial aneurysm’s differential expression gene. Part II: To compare the genotype frequency and A allele frequency of COL3A1exon30 + 2209A/G polymorphism in 98 patients with intracranial aneurysms and 116 controls by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method. Part III: 76 patients (31 male, 45 female, age is 30 to 78, mean 42.56 years ) with narrow neck aneurysm were collected, The subarachnoid hemorrhage patients whose aneurysm endovascular embolotherapy in 3 days is acute stage treatment, it has 21 cases. The subarachnoid hemorrhage patients whose aneurysm not in blood vessel embolotherapy in 3 days will embolotherapy in blood vessel after 2 weeks. 50 cases display accidental subarachnoid hemorrhage, 11 cases display ptosis, 9 diplay adventitions headache, 6 display visual disorder. According to Hunt-Hess, Degree I has 16 cases, Degree II has 34cases, Degree III has 23 cases, Degree IV has 3 cases. According to aneurysm neck absolute value and aneurysm body/ aneurysm neck contrast, 76 cases are all narrow aneurysm (aneurysm neck≤4mm, aneurysm body/aneurysm neck>2). The magnitude of aneurysm: the small ( < 5mm) is 39, medium-sized (5～10mm) is 36, the large (10～20mm) is 5. Adopting Seldinger technique piqure cannula throughout arteria cruralis, and use electrolyse GDC embolism aneurysm through small trachea. Wide aneurysm is 16 cases, 5 male, 11 female, the age are 34～68, the average is 46 years old. Among the total, 9 cases has subarachnoid hemorrhage, 4 has running headache, 3 has ocular movement disorder, according to Hunt-Hess, Degree I has 3 cases, Degree II has 9, Degree III has 4. Adopting Seldinger technique piqure cannula throughout arteria cruralis, and use Neuroform embolism aneurysm through small trachea.RESULT: Part I :Compared with arteria temporalis superficial gene, intracranial aneurysm constit owns 174 differential expression gene in total. Functional analysis acquires, among the total it has 5 immune inflammation related gene, 12 contractile fiber cells related gene, 25 metabolism related gene, 18 base material remodeling degradation related gene, 2 apoptosis related gene, 2 blood clotting related gene, 2 cell multiplication related gene, 2 peroxidize related gene, 1 oncogene, 3 cell cycle control related gene, 8 cell adhesion related gene, 13 transcriptional control related gene, 8 electron transfer related gene, 20 signal transduction related gene, 6 cell metabolism related gene, 47 function unknown gene, and 169 express up-regulation gene, 5 express down regulation gene. Part II: The genotypes in patients with intracranial aneurysms were not significantly different from those in controls (P>0.05) . The A allelic gene frequency in patients with intracranial aneurysms (23.71%) was not significantly different from that in controls (15.52%)(P>0.05). 76 cases of narrow aneurysm recheck brain angiogra- phy after embolotherapy, 100% embolism has 55 cases, 90%～99% embolism has 16 cases, 70%～90% embolism has 2 cases, death has 2 cases, plants living has 1 cases, limbs hemiparesis has 4 cases. 6 patinets may see small spring coccygeal segments intrude to carry artery about 2～3mm, have anticoagulant therapy 3 months and have no Abnormal appearance after operation. 69 patients of this group obtain clinical follow-up visit 3～12 months after operation, no one has rehaemorrhagia, oculomotor palsy can complete recovery in 3～12 months after operation. 2 deaths and 1 plants living are all arteria basilaris top aneurysm, the 3 patients are all cut aneurysm when inserting small ductus, after balancing out calparine, tamponade aneurysm quickly. Recheck CT after operation, it is few blooding. In the 16 cases wide neck aneurysms, the stent of 1 case displaced after operation, 1 case formed thromboembolism. It is not found narrow in neuroform stents follow up 6～12 months.CONCLUSION: We consider to deploy gene array technique platform is the new strategy which research and analysis intracranial aneurysm’s nosogenesis, throughout utilizing gene array technique for intracranial aneurysm constitution’s differential expression gene to undertake large-scale analysis. The result indicates intracranial aneurysm’s happening is a kind of multiple factor synthetic process which multiple gene participates. Among the total, apoptosis abnormality, cell signal transduction, extracellular matrix’s degrdn remodeling, immunifaction and inflammation’s damage and artherosclerosis may be intracranial aneurysm formation’s important molecule mechanism. At the same time, people also discover same expressed augmented funct unknown gene, it wait for new study and research. The genetic polymorphism of COL3A1 is probably not related with the occurrence of intracranial aneurysms. Endovascular embolisation therapy of intracra- nial aneurysm is less traumatic with high curative rate. It is difficult to obliterate some special aneurysms such as giant aneurysm, aneurysms located in the cavernous sinus and petrosa, and aneurysms of posterior circulation with open surgery ,whereas these aneurysms can be treated successfully with GDC technique. The operator can not open skull of heavy pathogenetic condition, bad condition all over the body, acute stage morbidity and the failure of occlusion operation, can have endovascular embolotherapy. The subarachnoid hemorrhage patient in many times, accretion seriously around aneurysm, who has more risk in opening skull, can use this management. Neuroform stents binding GDC embolization therapy have a good effect for aneurysm with wide neck, which can prevent the inserted coils from springing out and thus avoid the parent artery of the aneurysm being occluded, leading to cerebral ischemia. It provides a new procedure for the treatment of aneurysm with wide neck.