近日，哈尔滨医科大学附属第一医院心血管外科主任刘宏宇教授课题组首次采用血管内纯水（蒸馏水）灌注法+高脂饲料饲养法，成功制作出一种简单易行、可控性强的血管内膜增生动物模型。利用此模型，有助于深入探讨血管内膜增生与内皮细胞损伤后的功能障碍、细胞迁移、血流动力学、炎症及氧化应激等多种因素密切相关的机制，揭示血管内膜增生性病变的“奥秘”。相关论文刊发在最新一期美国《心血管病理学》（Cardiovascular Pathology）杂志上。
刘宏宇教授
课题组研究发现，纯水（蒸馏水）可以通过导致血管管腔内的低渗透压环境，进而诱导内皮细胞发生肿胀、功能障碍，低渗性休克甚至凋亡。且这种低渗造成的内膜损伤不伴有弹力板等的副损伤。由此，刘宏宇等人推测这种低渗透压诱导的内膜损伤结合高脂血症可能促使血管内膜发生增生性病变，并随血管内纯水灌注时间延长而加重。所以这一新的内膜增生模型可能会具有灌注时间相关性的可控性的内膜增生性病变。
基于以上假设，课题组将40只新西兰白兔随机分为4组，统一进行2%的高胆固醇饲养1周，外科手术暴露各组兔子的右侧股动脉并予血管内纯水灌注。术后继续用相同的2%高胆固醇饲养，4周后取材各实验组兔的右侧股动脉。同时经主动脉内采血，测定所有兔的血清总胆固醇、甘油三酯、低密度脂蛋白和高密度脂蛋白水平。经统计学分析，得出结论，血管内纯水灌注法可诱导兔股动脉的内膜细胞出现低渗性损伤。在含2%高胆固醇的高脂饲料饲养条件下，这一低渗性损伤会诱导血管内膜发生增生性病变，且其病变的程度具有正性的灌注时间的相关性。
该模型增生性内膜病变具有显著的可控性。它的发明与应用将会进一步促进基础实验和临床研究、动物模型和人体疾病的有效结合，为今后临床有效地防治血管成形术后管腔再狭窄奠定坚实基础。
A novel model of intimal hyperplasia with graded hypoosmotic damage
Mowei Song, Hong-tao Shen, Jin-jin Cui, Xin-gang Zhou, Xin Zhong, Cheng-hai Peng, Hong-yu Liu, Ye Tian
Background The purpose was to develop a rabbit model of intimal hyperplasia with controllable lesion.
Methods Following 1 week of a 2% cholesterol diet, 32 New Zealand White male rabbits underwent right femoral arteries surgical perfusion with distilled water for 1, 3, 5, or 7 min (n=8/group). After a further 4 weeks of the same diet, serum total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein were measured in all rabbits. Intimal hyperplasia in histological sections of arteries were assessed by intimal proliferation ratio. Macrophage numbers and levels of proteins matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 2, and alpha smooth muscle actin in lesions were analyzed by immunohistochemistry.
Results Serum lipids levels showed no statistical difference between experimental groups. Intimal proliferation ratio increased gradually with perfusion time, and a positive linear correlation was calculated between intimal proliferation ratio and duration of distilled water perfusion. Similarly, number of macrophages and levels of matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 2, and alpha smooth muscle actin in lesions increased with perfusion time.
Conclusions A novel model of intimal hyperplasia was established by intravascular distilled water perfusion in high-cholesterol-fed rabbits. Importantly, this model exhibits time-dependent neointimal proliferation lesions that can be readily controlled in terms of extent, thus providing an avenue for further studies.
文献链接：A novel model of intimal hyperplasia with graded hypoosmotic damage
