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目的:探讨血管紧张素Ⅱ(AngⅡ)皮下灌泵诱导Apo E-/-小鼠建立腹主动脉瘤模型的特点和可行性。方法:选取8-10周龄雄性Apo E-/-小鼠,通过植入式微量渗透释放泵皮下泵入AngⅡ(1000 ng/kg·min),持续泵入28天;对照组小鼠泵入生理盐水28天。取材后,测量小鼠腹主动脉直径,固定包埋做石蜡切片进行HE及弹力纤维染色,用Real-time PCR方法检测腹主动脉中α-平滑肌肌动蛋白(α-SMA)和骨桥蛋白(OPN)的表达。结果:AngⅡ处理组小鼠成瘤率为80%,腹主动脉直径较生理盐水对照组明显增加(P<0.05);病理染色显示炎症细胞明显增多,弹力纤维断裂增多,胶原合成增多。小鼠腹主动脉α-SMA m RNA表达较对照组显著降低(P<0.05),而OPN m RNA表达较对照组明显增高(P<0.05)。结论:通过AngⅡ连续灌注28天可以诱导Apo E-/-小鼠发生腹主动脉瘤,腹主动脉平滑肌细胞由收缩型向分泌型转化可能作为小鼠腹主动脉瘤发生的鉴定及治疗靶点之一。
Objective: To investigate the characteristics and feasibility of establishing a model of abdominal aortic aneurysm in Apo E - / - mice induced by Ang Ⅱ subcutaneously. METHODS: Male Apo E - / - mice aged 8-10 weeks were injected subcutaneously with Ang Ⅱ (1000 ng / kg · min) via implanted micro osmotic release pump and pumped continuously for 28 days. The control mice were injected with Physiological saline 28 days. The diameter of the abdominal aorta was measured and the paraffin sections of the abdominal aorta were fixed and embedded for HE staining and elastic fiber staining. The a-SMA and α-SMA were detected by Real-time PCR in abdominal aorta. (OPN) expression. Results: The tumor formation rate of AngⅡ-treated mice was 80% and the diameter of abdominal aorta was significantly increased compared with that of saline control group (P <0.05). Pathological staining showed that the number of inflammatory cells increased, the cleavage of elastic fibers and collagen synthesis increased. The expression of α-SMA m RNA in abdominal aorta of mice was significantly lower than that in control group (P <0.05), while the expression of OPN m RNA was significantly higher than that in control group (P <0.05). CONCLUSION: Aorta aneurysms can be induced in Apo E - / - mice by continuous infusion of Ang Ⅱ for 28 days. The contractile to secretory transformation of the smooth muscle cells of the abdominal aorta may be used as the identification and therapeutic target of abdominal aortic aneurysm in mice one.