颅内外血管重建术治疗成人烟雾病与烟雾病动物模型的构建

发布时间：2018-08-29 17:15

【摘要】：目的:探讨分析直接、间接与联合颅内外血管重建术治疗成人烟雾病的临床疗效,增加成人烟雾病的诊治经验;利用免疫诱导法(局部注射异种血清)构建烟雾病动物模型。方法:(1)收集2013年01月至2016年01月在济宁医学院附属医院行颅内外血管重建术,且为成人烟雾病患者的临床资料。对纳入本研究的患者分别于术后1月、3月、6月、1年,之后每6个月随访1次。随访方式为电话、门诊或再次住院,随访内容包括临床症状变化、影像学改变、异常脑血管事件等。通过分析比较患者术前与术后改良Rankin评分(modified Rankin Scale score,mRS)、异常脑血管事件等变化情况评判颅内外血管重建术的临床疗效。(2)利用新西兰大白兔,采用免疫诱导法(局部注射异种血清)构建烟雾病动物模型。将所有兔随机分为实验组及对照组,每组各5只。实验组诱导剂为特种马血清,对照组用0.9%生理盐水替代特种马血清。诱导剂注射剂量为1ml/次,频率为1次/周。实验组与对照组注射部位、注射频率、注射液体量一致。分别于干预前及干预后的1月、3月、6月行颅脑CTA或者MRA,并测量注射部位颈动脉直径。干预6月后分别取实验组及对照组注射部位颈动脉做病理切片,比较病理变化。结果:(1)112例患者纳入本研究,49例行直接颅内外血管重建术,41例行间接颅内外血管重建术,22例行联合颅内外血管重建术。三种术式的患者的年龄、性别等一般资料差异无统计学意义(P0.05)。三种术式的患者术后12月mRS评分均有不同程度的降低,与术前相比差异有统计学意义(wilcoxon符号秩和检验,P0.05,CI:95%)。直接术式术后临床症状缓解率为85.7%,间接术式为78.0%,联合术式为86.4%,直接术式、联合术式的临床症状缓解率优于间接术式,但差异并无统计学意义(卡方检验,χ2总体=1.146,P总体=0.5640.05)。Kaplan-Meier生存分析结果显示,随着术后随访时间的延长,三种术式患者的异常脑血管事件发生率逐渐下降,各术式术后脑血管事件再发生率比较,其差异无统计学意义(Mantel-Cox检验,P=0.6770.05,CI:95%)。(2)局部注射异种血清6月后,实验组与对照组相比,颈动脉直径未见明显狭窄,颅底未见形成异常血管网。注射部位颈动脉病理结果显示无明显炎性改变。结论:(1)直接、间接及联合颅内外血管重建术是治疗成人烟雾病的有效方法。(2)我们目前单中心的初步研究结果显示,直接、间接及联合颅内外血管重建术治疗成人烟雾病的临床疗效没有明显差别。(3)通过局部注射异种血清未能造成兔颈动脉狭窄,因此,免疫炎症反应是否可以独立地引起烟雾病以及通过免疫诱导法能否成功构建烟雾病动物模型有待进一步研究证实。
[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.
【学位授予单位】：济宁医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R651.12

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