【摘要】：目的:探討分析直接、間接與聯(lián)合顱內(nèi)外血管重建術治療成人煙霧病的臨床療效,增加成人煙霧病的診治經(jīng)驗;利用免疫誘導法(局部注射異種血清)構建煙霧病動物模型。方法:(1)收集2013年01月至2016年01月在濟寧醫(yī)學院附屬醫(yī)院行顱內(nèi)外血管重建術,且為成人煙霧病患者的臨床資料。對納入本研究的患者分別于術后1月、3月、6月、1年,之后每6個月隨訪1次。隨訪方式為電話、門診或再次住院,隨訪內(nèi)容包括臨床癥狀變化、影像學改變、異常腦血管事件等。通過分析比較患者術前與術后改良Rankin評分(modified Rankin Scale score,mRS)、異常腦血管事件等變化情況評判顱內(nèi)外血管重建術的臨床療效。(2)利用新西蘭大白兔,采用免疫誘導法(局部注射異種血清)構建煙霧病動物模型。將所有兔隨機分為實驗組及對照組,每組各5只。實驗組誘導劑為特種馬血清,對照組用0.9%生理鹽水替代特種馬血清。誘導劑注射劑量為1ml/次,頻率為1次/周。實驗組與對照組注射部位、注射頻率、注射液體量一致。分別于干預前及干預后的1月、3月、6月行顱腦CTA或者MRA,并測量注射部位頸動脈直徑。干預6月后分別取實驗組及對照組注射部位頸動脈做病理切片,比較病理變化。結果:(1)112例患者納入本研究,49例行直接顱內(nèi)外血管重建術,41例行間接顱內(nèi)外血管重建術,22例行聯(lián)合顱內(nèi)外血管重建術。三種術式的患者的年齡、性別等一般資料差異無統(tǒng)計學意義(P0.05)。三種術式的患者術后12月mRS評分均有不同程度的降低,與術前相比差異有統(tǒng)計學意義(wilcoxon符號秩和檢驗,P0.05,CI:95%)。直接術式術后臨床癥狀緩解率為85.7%,間接術式為78.0%,聯(lián)合術式為86.4%,直接術式、聯(lián)合術式的臨床癥狀緩解率優(yōu)于間接術式,但差異并無統(tǒng)計學意義(卡方檢驗,χ2總體=1.146,P總體=0.5640.05)。Kaplan-Meier生存分析結果顯示,隨著術后隨訪時間的延長,三種術式患者的異常腦血管事件發(fā)生率逐漸下降,各術式術后腦血管事件再發(fā)生率比較,其差異無統(tǒng)計學意義(Mantel-Cox檢驗,P=0.6770.05,CI:95%)。(2)局部注射異種血清6月后,實驗組與對照組相比,頸動脈直徑未見明顯狹窄,顱底未見形成異常血管網(wǎng)。注射部位頸動脈病理結果顯示無明顯炎性改變。結論:(1)直接、間接及聯(lián)合顱內(nèi)外血管重建術是治療成人煙霧病的有效方法。(2)我們目前單中心的初步研究結果顯示,直接、間接及聯(lián)合顱內(nèi)外血管重建術治療成人煙霧病的臨床療效沒有明顯差別。(3)通過局部注射異種血清未能造成兔頸動脈狹窄,因此,免疫炎癥反應是否可以獨立地引起煙霧病以及通過免疫誘導法能否成功構建煙霧病動物模型有待進一步研究證實。
[Abstract]:Objective: to investigate the clinical effect of direct, indirect and combined intracranial and external vascular reconstruction in the treatment of adult moyamoya disease, and to increase the experience of diagnosis and treatment of adult moyamoya disease, and to establish an animal model of moyamoya disease by immunoinduction (local injection of heterogeneous serum). Methods: (1) the clinical data of adult patients with moyamoya disease were collected from January 2013 to January 2016 in the affiliated Hospital of Jining Medical College. Patients included in the study were followed up for 1 month, 3 months, 6 months, and 1 year after surgery. The follow-up included changes in clinical symptoms, imaging changes, abnormal cerebrovascular events and so on. By analyzing and comparing the changes of preoperative and postoperative modified Rankin score (modified Rankin Scale score,mRS), abnormal cerebrovascular events and other changes in patients, the clinical efficacy of intracranial and external vascular reconstruction was evaluated. (2) New Zealand white rabbits were used. An animal model of moyamoya disease was established by immuno-induction (local injection of heterologous serum). All rabbits were randomly divided into experimental group and control group with 5 rabbits in each group. The experimental group was induced by special horse serum and the control group was replaced by 0.9% normal saline. The dose of inducer was 1ml/ and the frequency was once a week. The injection site, injection frequency and volume of injection were the same in the experimental group and the control group. Craniocerebral CTA or MRA, were performed before intervention and 1 month, 3 months and 6 months after intervention, and the diameter of carotid artery at injection site was measured. After 6 months of intervention, the experimental group and the control group were taken to make pathological sections of the carotid artery at injection site, and the pathological changes were compared. Results: (1) one hundred and twelve patients were included in this study. 49 cases underwent direct intracranial and external vascular reconstruction and 41 cases underwent indirect intracranial and external vascular reconstruction. 22 cases were combined with external intracranial vessel reconstruction. There was no significant difference in age, sex and other general data among the three types of operation (P0.05). At 12 months after operation, the mRS scores of the three types of patients were significantly lower than those of the patients before operation (P < 0.05 CI: 95%, P < 0.05), and the difference was statistically significant (P < 0.05). The relief rate of clinical symptoms was 85.7% in direct operation, 78.0 in indirect operation and 86.4 in combined operation. The clinical symptom relief rate of direct operation and combined operation was better than that of indirect operation. The results of Kaplan-Meier survival analysis showed that the incidence of abnormal cerebrovascular events decreased gradually with the prolongation of postoperative follow-up time in the three types of patients, but the difference was not statistically significant (chi-square test, 蠂 2 total 1.146P = 0.5640.05), the results of Kaplan-Meier survival analysis showed that the incidence of abnormal cerebrovascular events decreased gradually with the extension of postoperative follow-up time. There was no significant difference in the recurrence rate of cerebrovascular events between the two groups (Mantel-Cox test (P 0.677 0.05% CI 95%). (2). Six months after local injection of xenogeneic serum, the diameter of carotid artery in the experimental group was not significantly narrower than that in the control group, and no abnormal vascular network was found in the skull base. No significant inflammatory changes were found in the carotid artery at the injection site. Conclusion: (1) Direct, indirect and combined revascularization is an effective method for the treatment of adult moyamoya disease. There was no significant difference between indirect and combined intracranial and external vascular reconstruction in the treatment of adult moyamoya disease. (3) Local injection of xenogeneic serum failed to cause carotid artery stenosis in rabbits. Whether the immune inflammatory reaction can cause moyamoya disease independently and whether the animal model of moyamoya disease can be successfully constructed by immune induction needs further study.
【學位授予單位】：濟寧醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R651.12

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