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一种高血压危象急症的实验模型:自发性高血压大鼠长期高脂肪饮食后急性血管收缩应激。

An experimental model for hypertensive crises emergencies: Long-term high-fat diet followed by acute vasoconstriction stress on spontaneously hypertensive rats.

机构信息

1 Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-marketed TCM, Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. China.

2 Guangdong Zhongsheng Pharmaceutical Co., Ltd, Dongguan 523325, P.R. China.

出版信息

Exp Biol Med (Maywood). 2018 Mar;243(5):481-495. doi: 10.1177/1535370218759270. Epub 2018 Feb 14.

Abstract

Currently, the prevention and treatment of hypertensive crises especially when it occurs with serious adverse outcomes have led to worldwide controversy. Despite of clinical possibilities of multiple agents, clinical failures still occur frequently. Therefore, early evaluations and observations of different therapies on appropriate animals should be emphasized. In the present study, an animal model for hypertensive crises emergencies was firstly established and experimentally testified. Five-month-male spontaneously hypertensive rat was consecutively fed with 60%-Kcal fat diet for four, six, and eight weeks with body weight and blood pressure monitored every two weeks, and then followed by an acute vasoconstriction stress of 5-min ice-bath treatment in the 4-h time interval of two adrenaline injections (0.8 mg/kg). Forty-four biochemical parameters were detected, covering hepatic and renal function, blood glucose and lipid levels, myocardial enzymes and energy metabolisms, blood coagulative and anti-coagulative system, oxidative stress and anti-inflammatory cytokine, blood viscosity, and RAAS system. Six tissues including heart, brain, liver, kidney, coronary arteries, and mesenteries were removed for pathological observations with hematoxylin-eosin staining. As a result, multi-organ dysfunctions in the heart, brain, liver, kidney, vascular endothelium, and blood system were testified in the modeling rats at weeks 6 and 8. In conclusion, severe consequences of this animal model were highly similar to those in hypertensive crises emergencies, which could be further utilized in the early intervention of hypertensive crises emergencies including the possible risk factors control and efficient therapies assessment. Impact statement In the late 90s, numerous reports predicted that 1-2% of hypertensive individuals would undergo hypertensive crises (HPC) and figures reached as high as 7% when no antihypertensive therapies were administrated. Currently, clinical failures appear frequently due to the improper or excessive medication regimen instead of the illness itself. Therefore, early evaluations and observations of HPC on appropriate animal models ahead of patients should be discussed and emphasized more widely. In the present study, an appropriate animal model for HPC emergencies was firstly established, in which the consequences of long-term high-fat diet feeding followed by an acute vasoconstriction stress on the spontaneously hypertensive rats were experimentally testified. The proposed model would have a wide application prospects in early intervention of HPC emergencies including the controls of possible risk factors and assessments of efficient therapies.

摘要

目前,高血压危象的防治,尤其是当它导致严重不良后果时,已在全球范围内引起争议。尽管有多种药物可供临床选择,但临床失败仍经常发生。因此,应强调在适当的动物身上对不同治疗方法进行早期评估和观察。在本研究中,首次建立并实验验证了高血压危象急症的动物模型。将 5 月龄雄性自发性高血压大鼠连续喂食 60%的高脂肪饮食 4、6 和 8 周,每两周监测体重和血压,然后在两次肾上腺素注射(0.8mg/kg)之间的 4 小时间隔内进行 5 分钟冰浴急性血管收缩应激。检测了 44 项生化参数,涵盖肝肾功能、血糖和血脂水平、心肌酶和能量代谢、凝血和抗凝系统、氧化应激和抗炎细胞因子、血液粘度以及 RAAS 系统。取出心脏、大脑、肝脏、肾脏、冠状动脉和肠系膜等 6 种组织进行苏木精-伊红染色的病理观察。结果表明,在第 6 周和第 8 周的建模大鼠中证实了心脏、大脑、肝脏、肾脏、血管内皮和血液系统的多器官功能障碍。总之,该动物模型的严重后果与高血压危象急症非常相似,可进一步用于高血压危象急症的早期干预,包括可能的危险因素控制和有效治疗的评估。

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