摘要
脑出血是致死致残率最高的脑卒中类型,至今仍无明确有效的治疗手段。缺乏与脑出血临床特征相契合的动物模型可能是阻碍其研究的根本原因。本文通过回顾现有自发性脑出血小鼠模型,共发现2种高血压脑出血模型、1种自发性深部脑出血模型和5种脑淀粉样血管病模型。高血压模型其中一种是双转基因小鼠,通过过表达人肾素和血管紧张素原,导致小鼠高血压。然而,该模型脑出血的发生需要结合高盐饮食和一氧化氮合酶抑制剂。另一种则采用皮下缓慢释放血管紧张素Ⅱ和抑制一氧化氮合酶导致慢性高血压,随后急性注射血管紧张素Ⅱ进一步提升血压造成血压剧烈波动诱导脑出血发生。自发性深部脑出血模型可能是除高血压因素外研究深部脑出血最理想的小鼠模型。5种淀粉样血管病模型均建立在淀粉样前体蛋白突变型的转基因小鼠,但关于其脑出血特征的研究比较匮乏。目前自发性脑出血仍缺少公认的广泛使用的动物模型,理想的脑出血模型应能最大限度模拟疾病的发展特征,只有开展符合临床实际需要的脑出血基础研究,才有望为脑出血防治提供新的有效靶点。
Intracerebral hemorrhage(ICH)is the type of stroke with the highest mortality and disability.There is still no effective treatment.The scarcity of animal models that strictly simulate the clinical characteristics of ICH may be the root cause for hindering the research of ICH.This article reviews the existing spontaneous ICH mouse models and found two hypertensive ICH models,one spontaneous deep ICH model and five cerebral amyloid angiopathy models.One of the hypertensive models was double transgenic mice,which overexpressed human renin and angiotensinogen,leading to hypertension in mice.However,the occurrence of this model of ICH required a combination of a high-salt diet and a nitric oxide synthase inhibitor.The other hypertensive model utilized slow subcutaneous release of angiotensinⅡand inhibition of nitric oxide synthase to cause chronic hypertension,followed by acute injection of angiotensinⅡto further increase blood pressure and cause dramatic fluctuations in blood pressure to induce ICH.The spontaneous deep ICH model may be the most ideal mouse model for studying ICH except for hypertension.In addition,the five cerebral amyloid angiopathy models were all established in transgenic mice with amyloid precursor protein mutations,but the research on the characteristics of ICH was relatively scarce.At present,spontaneous ICH still lacks widely recognized and used animal models.The ideal ICH model should be able to simulate the development characteristics of the disease to the greatest extent.Only by carrying out ICH basic research that meets clinical needs can it be expected to provide new and effective targets on ICH prevention and treatment.
作者
张钦
杨清武
Zhang Qin;Yang Qingwu(Department of Neurology,Second Affiliated Hospital(Xinqiao Hospital),the Army Medical University(Third Military Medical University),Chongqing 400037,China)
出处
《中华脑血管病杂志（电子版）》
2021年第2期64-69,共6页
Chinese Journal of Cerebrovascular Diseases(Electronic Edition)
基金
重庆市自然科学基金创新群体科学基金,卒中后脑高级功能障碍的神经环路解析的基础研究(cstc2019jcyj-cxttX0005)。
关键词
自发性脑出血
动物模型
高血压
脑淀粉样血管病
Spontaneous intracerebral hemorrhage
Animal models
Hypertension
Cerebral amyloid angiopathy
