周细胞对失血性休克大鼠血管通透性的保护作用  

Protective effect of pericytes against vascular leakage in rats with hemorrhagic shock

作　　者：何霜霜 朱娱[1] 周赫男 王洪晨 李涛[1] 刘良明[1] HE Shuangshuang;ZHU Yu;ZHOU Henan;WANG Hongchen;LI Tao;LIU Liangming(State Key Laboratory of Trauma,Burns and Combined Injury,Institute of Surgery Research,Daping Hospital,Army Medical University(Third Military Medical University),Chongqing,400042,China)

机构地区：[1]陆军军医大学(第三军医大学)野战外科研究所战伤休克与输血研究室创伤、烧伤与复合伤国家重点实验室,重庆400042

出　　处：《第三军医大学学报》2020年第19期1882-1889,共8页Journal of Third Military Medical University

基　　金：国家自然科学基金重点项目(81830065)。

摘　　要：目的探讨周细胞(pericyte, PC)对失血性休克(hemorrhagic shock, HS)大鼠血管渗漏的保护作用。方法采用失血性休克(血压30 mmHg,维持3 h)模型,将12~24周龄SD大鼠(雌雄各半,体质量200~220 g)分成4组(n=16):假手术组(Sham组)、失血性休克组(HS组)、乳酸林格氏液治疗组(LR组)、PC治疗组(PC组),治疗组在失血性休克大鼠血压至30 mmHg,维持3 h后开始治疗,治疗12 h后取材,观察不同处理组大鼠肺静脉上的周细胞数量、肺血管及肠系膜微血管的通透性、内皮紧密连接ZO-1和黏附连接VE-cadherin的表达变化。结果与正常对照组相比,失血性休克大鼠血管渗漏明显加重(P<0.05),周细胞数量减少,内皮细胞超微结构紧密连接破坏,内皮细胞间紧密连接ZO-1和黏附连接VE-cadherin的表达明显降低(P<0.05)。LR治疗12 h后能够轻微降低失血性休克大鼠的血管通透性;紧密连接开放程度轻微降低,内皮细胞间紧密连接ZO-1和黏附连接VE-cadherin的表达轻微升高。与LR组相比,PC治疗12 h后,失血性休克大鼠肺静脉上周细胞数量增加;细胞形态恢复,超微结构紧密连接开放程度显著降低;内皮细胞间紧密连接ZO-1和黏附连接VE-cadherin的表达明显著升高(P<0.05),恢复至接近正常水平;血管渗漏明显改善,肠系膜微血管通透性显著降低。结论周细胞对失血性休克大鼠血管渗漏具有明显的保护作用。Objective To investigate the protective effect of pericytes(PCs) against vascular leakage in rats with hemorrhagic shock. Methods Sixty-four 12-to 24-week-old SD rats weighing 200~220 g were randomized equally into sham-operated group, hemorrhagic shock group(HS group), Ringer’s lactate solution treatment group(LR group), and PC treatment group(PC group). In the latter 3 groups, rat models of hemorrhagic shock were established by lowering the blood pressure to 30 mmHg, which was maintained for 3 h. Tissue samples were collected 12 h after corresponding treatment for determination of the number of pericytes, vascular permeability of the pulmonary vessels and the mesenteric microvessels, and expressions of zonula occludens 1(ZO-1) and VE-cadherin. Results The vascular permeability was increased(P<0.05) and the number of pericytes and expressions of ZO-1 and VE-cadherin were decreased significantly(P<0.05) in rats with hemorrhagic shock compared with the sham-operated rats. At 12 h after LR treatment, the vascular permeability was slightly reduced, the tight junction between the endothelial cells was moderately improved and the expression levels of ZO-1 and VE-cadherin were mildly increased in rats with hemorrhagic shock. At 12 h after PC treatment, the number of pericytes in the pulmonary vein was increased, the cell morphology and tight junction between the endothelial cells were restored, and the expressions of ZO-1 and VE-cadherin were increased significantly to nearly the normal levels in rats with hemorrhagic shock(P<0.05);the mesenteric microvascular permeability and vascular leakage were improved significantly after treatment with PCs. Conclusion PC infusion produces significantly protective effect against vascular leakage in rats with hemorrhagic shock.

关 键 词：周细胞 失血性休克 血管通透性 ZO-1 VE-CADHERIN 

分 类 号：R322.12[医药卫生—人体解剖和组织胚胎学] R329.27[医药卫生—基础医学]