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目的建立一种可靠的小鼠高血压及血管重塑模型。方法 C57BL/6小鼠皮下埋植微渗透泵,随机分为3组:高血压血管重塑组、单纯性血管重塑组和对照组,分别在体灌注血管紧张素Ⅱ(AngⅡ)400、100ng/(kg·min)和生理盐水,共28d;0、1、2、3、7、14、21和28d监测收缩压、舒张压、平均动脉压及心率变化;0、3、7和14d检测血清及血管组织中AngⅡ水平;观察AngⅡ灌注28d后主动脉及三级肠系膜动脉的形态学变化,血管壁中Ⅰ/Ⅲ型胶原表达改变。结果 400ng/(kg·min)AngⅡ灌注后第2天小鼠血压开始升高[400ng/(kg·min)AngⅡ组比对照组,收缩压(118.5±3.7)比(102.6±3.1)mm Hg,P=0.002;舒张压(88.1±4.6)比(62.6±3.4)mm Hg,P=0.001],随后血压持续升高,第7天到平台期并维持在高血压水平,而100ng/(kg·min)AngⅡ灌注后小鼠血压未见明显升高。两组模型小鼠在AngⅡ灌注后血清AngⅡ[400ng/(kg·min):3d比0d,(998±85)比(88±7)ng/L,P<0.01;100ng/(kg·min):3d比0d,(211±25)比(95±9)ng/L,P=0.001]及主动脉组织中AngⅡ水平[400ng/(kg·min):3d比0d,(185±15)比(135±11)ng/g,P=0.005;100ng/(kg·min):3d比0d,(149±8)比(132±9)ng/g,P=0.035;n=5]均升高,且28d后主动脉及三级肠系膜动脉发生明显的重塑改变,Ⅰ/Ⅲ型胶原mRNA及蛋白表达增加,400ng/(kg·min)组血管重塑程度更加显著。结论通过微渗透泵在体灌注AngⅡ诱导高血压血管重塑模型和单纯性血管重塑模型具有操作简单、成功率高、易复制、稳定可靠、造模时间短等特点,可以广泛用于高血压发病机制研究和抗高血压药物的筛选。
Objective To establish a reliable model of hypertension and vascular remodeling in mice. Methods C57BL / 6 mice were subcutaneously implanted with micro-osmotic pump and randomly divided into 3 groups: hypertensive vascular remodeling group, simple angiogenesis remodeling group and control group. The rats were infused with 400,100ng of angiotensin II systolic blood pressure, diastolic blood pressure, mean arterial pressure and heart rate were monitored at 0, 1, 2, 3, 7, 14, 21 and 28 days. The level of AngⅡ in serum and vascular tissue was observed. The morphological changes of the aorta and the third grade mesenteric artery were observed 28 days after Ang Ⅱ perfusion, and the expression of type Ⅰ / Ⅲ collagen in the vessel wall was changed. Results The blood pressure of 400 ng / (kg · min) Ang Ⅱ group was significantly higher than that of the control group at 400 ng / (kg · min) Ang Ⅱ, the systolic blood pressure (118.5 ± 3.7) was (102.6 ± 3.1) mm Hg, P = 0.002; diastolic blood pressure (88.1 ± 4.6) vs (62.6 ± 3.4) mm Hg, P = 0.001], followed by a sustained rise in blood pressure from day 7 to plateau and maintenance of hypertension, whereas 100 ng / (kg · min) No significant increase in blood pressure of mice after Ang Ⅱ perfusion. The levels of Ang Ⅱ [400 ng / (kg · min): 3d than 0d, (998 ± 85) vs (88 ± 7) ng / L, P <0.01 and 100ng / (kg · min) (95 ± 9) ng / L, (P <0.001)] and the level of AngⅡ in aortic tissue [400 ng / (kg · min): 3d vs 0d, (185 ± 15) (135 ± 11) ng / g, P = 0.005; 100 ng / (kg · min): 3d vs 0d, (149 ± 8) vs (132 ± 9) ng / g, P = 0.035; After 28 days, the aortic and tertiary mesenteric arteries were significantly remodeled. The mRNA and protein expressions of type Ⅰ / Ⅲ collagen increased, and the degree of vascular remodeling was more pronounced in 400 ng / (kg · min) group. Conclusion Microinvasive perfusion of angiotensin Ⅱ-induced angiotensin Ⅱ type angiotensin Ⅱ (AngⅡ) -mediated vascular remodeling and simple vascular remodeling with micro-osmotic pump has the advantages of simple operation, high success rate, easy replication, stable and reliable, short modeling time and so on. It can be widely used in hypertension Pathogenesis and Antihypertensive Drug Screening.