高原缺氧条件下颅内静脉窦血栓形成动物模型的建立与评价  

Establishment and evaluation of animal models of intracranial venous sinus thrombosis under plateau hypoxia

作　　者：艾合买提·哈斯木 郑刚 张开元 侯效胜 邹志浩 Aihemati Hasmul;Zheng Gang;Zhang Kaiyuan;Hou Xiaosheng;Zou Zhihao(Department of Neurosurgery,General Hospital of Xinjiang Military Region of PLA,Urumqi 830000,China)

机构地区：[1]中国人民解放军新疆军区总医院神经外科,乌鲁木齐830000

出　　处：《中华神经医学杂志》2024年第5期443-449,共7页Chinese Journal of Neuromedicine

基　　金：新疆维吾尔自治区自然科学基金(2022D01C844);军队后勤科研重大项目(ALJ22J002)。

摘　　要：目的通过模拟高原低压缺氧环境,构建高原缺氧条件下颅内静脉窦血栓(CVST)模型,进一步验证高原缺氧条件对CVST形成的作用。方法48只8周龄雄性SD大鼠按照随机数字表法分为4组:假手术组、高原假手术组、CVST组、高原CVST组,每组12只。CVST组、高原CVST组大鼠通过氯化铁湿敷法建立CVST模型,高原CVST组大鼠造模后即刻进低压氧舱中饲养2 d,模拟海拔5000 m高原缺氧环境(气压54.047 kPa,氧浓度为10%~11%,18~23℃)。假手术组大鼠仅分离骨瓣和硬脑膜,不使用滤纸贴敷,不进低压氧舱饲养。高原假手术组仅分离骨瓣和硬脑膜,不使用滤纸贴敷,进低压氧舱饲养2 d,模拟海拔5000 m高原缺氧环境。采用多普勒血流仪检测4组大鼠造模前及造模后48 h时颅内静脉窦血流情况。造模后6 h、24 h、48 h每组各取4只大鼠处死后剪出上矢状窦血栓处血管(假手术组、高原假手术组取上矢状窦处同等长度血管)并称重;同时计算每组大鼠脑组织含水量。造模后24 h,取大鼠脑、心脏、肝脏、肺、肾脏组织及静脉血管行HE染色、甲苯胺蓝染色(仅脑组织)。结果(1)多普勒血流仪检测结果显示造模前4组大鼠颅内静脉窦血流信号正常;造模48 h后,假手术组与高原假手术组大鼠颅内静脉窦血流信号正常,CVST组与高原CVST组大鼠颅内静脉窦血流信号明显减弱。(2)直到造模后48 h,假手术组大鼠一直未形成血栓。造模后6 h、24 h及48 h,CVST组[(15.44±1.90)mg、(12.63±1.26)mg、(7.85±0.68)mg]和高原CVST组大鼠血栓重量[(20.38±1.67)mg、(24.93±2.37)mg、(20.90±1.30)mg]均明显高于高原假手术组[(2.55±0.38)mg、(2.19±0.30)mg、(1.75±0.31)mg],高原CVST组大鼠血栓重量均明显高于CVST组,差异均有统计学意义(P<0.05)。横向比较方面,高原假手术组、CVST组大鼠3个时间点血栓重量依次减少,差异有统计学意义(P<0.05);而高原CVST组大鼠造模后24 h时血栓重量较6 h明显�Objective To construct the intracranial venous sinus thrombosis(CVST)models under plateau hypoxia by simulating plateau hypoxic condition,and further clarify the role of plateau hypoxa in CVST.Methods Forty-eight 8-week-old male SD rats were randomly divided into sham-operated group,plateau sham-operated group,CVST group,and plateau CVST group(n=12).CVST models in the CVST group and plateau CVST group were established by ferric chloride wet dressing,and rats in the plateau CVST group were kept in a low-pressure oxygen chamber for 2 d immediately after modeling to simulate plateau hypoxic condition at an altitude of 5,000 m(barometric pressure of 54.047 kPa,oxygen concentration of 10%-11%,and temperature of 18-23°C).Only the bone flap and dura mater were separated in rats of the sham-operated group,without low-pressure oxygen condition or filter paper dressing.Only the bone flap and dura mater were separated in rats of the plateau sham-operated group,with plateau hypoxic condition at an altitude of 5,000 m for 2 d and without filter paper dressing.Intracranial venous sinus blood flow was detected by Doppler flowmetry before and 48 h after modeling.At 6,24,and 48 h after modeling,4 rats in each group were sacrificed;blood vessels at the thrombus of superior sagittal sinus(blood vessels at the superior sagittal sinus in the sham-operated group and plateau sham-operated group)were cut out and weighed;meanwhile,water contents of the brain tissues were calculated.HE staining was employed in the brain,heart,liver,lung,and kidney tissues and veins,and toluidine blue staining was peformed in the brain tissues only at 48 h after modeling.Results(1)Doppler flowmetry indicated that intracranial venous sinus blood flow was normal in the 4 groups before modeling;intracranial venous sinus blood flow signals were normal in the sham-operated group and plateau sham-operated group and obviously weakened in the CVST group and plateau CVST group 48 h after modeling.(2)No thrombus was formed in the sham-operated group 48 h after mode

关 键 词：颅内静脉窦 血栓 高原 缺氧 氯化铁湿敷 

分 类 号：R743[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]