β-氨基丙腈联合血管紧张素Ⅱ诱导大鼠主动脉夹层模型的建立

Establishment of a rat model with aortic dissection induced byβ-aminopropionitrile combined with angiotensinⅡ

目的探讨β-氨基丙腈(β-aminopropionitrile,BAPN)联合血管紧张素Ⅱ(AngiotensinⅡ,Ang-Ⅱ诱导建立SD大鼠主动脉夹层(aortic dissection,AD)模型的最佳给药组合及其并发症。方法选取3周龄雄性SD大鼠42只,使用完全随机法将其分为7组,即A组(0.25%BAPN组)、B组(0.40%BAPN组)、C组(0.80%BAPN组)、D组[1 g/(kg·d)BAPN组]、E组[1 g/(kg·d)BAPN+1μg/(kg·min)生理盐水组]、F组[1 g/(kg·d)BAPN+1μg/(kg·min)Ang-Ⅱ组]、G组(对照组),每组6只。干预周期为4周(E、F组为4周+5 d),实验过程中如有大鼠死亡则立即解剖,干预结束后,存活大鼠通过给予戊巴比妥钠处死,分离、留取全程主动脉。通过苏木精-伊红染色从病理形态学特征上观察主动脉变化。结果BAPN干预4周后各干预组生存率差异无统计学意义(P>0.05);植入微渗泵5 d后,E组大鼠生存率高于F组(P=0.008),AD发生率低于F组(P=0.001);BAPN可影响大鼠的饮食量和饮水量;BAPN干预4周后G组大鼠体重大于各干预组(P<0.05);BAPN联合Ang-Ⅱ可使大鼠主动脉中膜增厚、弹性纤维断裂、排列紊乱,伴炎症细胞浸润,符合AD病理形态学改变;BAPN还可对精神状态和胃肠道造成影响。结论通过1g/(kg·d)BAPN联合1μg/(kg·min)Ang-Ⅱ的给药组合可稳定地建立大鼠AD模型,这将对深入研究AD发病机制和治疗靶点提供一种稳定的载体,但该过程中出现的并发症是一种不稳定因素,如何平衡AD模型建立过程中BAPN对其他组织器官的影响还有待进一步研究。

Objective To investigate the optimal administration combination ofβ-aminopropionitrile(BAPN)and AngiotensinⅡ(Ang-Ⅱ)in the establishment of SD rat aortic dissection(AD)model and the related complications.Methods Forty-two three-week-old male SD rats were randomly divided into 7 groups:a group A(0.25%BAPN),a group B(0.40%BAPN),a group C(0.80%BAPN),a group D[1 g/(kg·d)BAPN],a group E[1 g/(kg·d)BAPN+1μg/(kg·min)saline],a group F[1 g/(kg·d)BAPN+1μg/(kg·min)Ang-Ⅱ]and a group G(control group).There were 6 rats in each group.The intervention period was 4 weeks(groups E and F were 4 weeks+5 days).Rats were dissected immediately if they died during the experiment.After the intervention,the surviving rats were sacrificed by pentobarbital sodium,and the whole aorta was separated and retained.Hematoxylin-eosin staining was used to observe the changes of aorta from the pathological morphology.Results There was no statistical difference in the survival rate among the groups after 4 weeks of BAPN intervention(P>0.05).After 5 days of mini-osmotic pumps implantation,the survival rate of rats was higher in the group E than that in the group F(P=0.008),and the incidence of AD in the group E was lower than that in the group F(P=0.001).BAPN could affect the food and water intake of rats.After BAPN intervention for 4 weeks,the body weight of rats in the group G was higher than those in the intervention groups(P<0.05).BAPN combined with Ang-Ⅱcould make the aortic intima thick,elastic fiber breakage,arrangement disorder,and inflammatory cell infiltration in rats,which conformed to the pathological and morphological changes of AD.BAPN could also affect mental state and gastrointestinal tract.Conclusion The combination of BAPN[1 g/(kg·d)]and Ang-Ⅱ[1μg/(kg·min)]can stably establish AD model in rats,which will provide a stable carrier for further study of the pathogenesis and therapeutic targets of AD.However,the complications in this process are an unstable factor.How to balance the influence of BAPN on other tissues and organs in the process of AD model establishment remains to be further studied.