血管紧张素Ⅱ对小鼠主动脉壁结构的影响及其机制探讨

Effect and mechanism of angiotensin Ⅱ on aorta wall structure dissection in mices

目的观察血管紧张素Ⅱ对小鼠主动脉壁结构的影响,并探讨其机制。方法将8月龄C57BL/6J小鼠40只,随机分为试验组和对照组各20只。试验组予4.5 mg/(kg.d)血管紧张素Ⅱ腹腔注射,对照组予12 mg/(kg.d)去甲肾上腺素腹腔注射,每次注射后30 min用鼠尾测压器测量血压并记录,持续14 d。14 d后处死小鼠,取出主动脉壁行病理检验观察动脉壁结构变化,并用免疫组织化学法检测小鼠主动脉壁组织中的基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶-2(MMP-2)和金属蛋白酶组织抑制因子-2(TIMP-2)。结果实验过程中试验组小鼠血压为(134.5±3.5)mmHg,对照组为(132.9±2.7)mmHg,P>0.05。试验组12只小鼠主动脉管壁中膜变薄,部分可见断裂,7只形成明显主动脉夹层;对照组小鼠主动脉壁则未见明显变化。试验组小鼠主动脉壁组织中MMP-9、MMP-2、TIMP-2表达量分别为0.451 3±0.022 1、0.508 4±0.013 1、0.623 8±0.014 2,对照组分别为0.285 7±0.011 3、0.381 4±0.020 3、0.354 5±0.021 3,两组相比P均<0.05。结论血管紧张素Ⅱ可能通过升高主动脉壁组织MMP-9、MMP-2和降低TIMP-2损伤小鼠主动脉壁,甚至引起主动脉夹层。

Objective To explore the effect and mechanism of angiotensin Ⅱ on aorta wall structure dissection in mices.Methods 40 C57BL/6J mices,healthy and 8 months old,were randomly divided into experimental group and control group,20 each.Mices in experimental group received angiotensin Ⅱ 4.5 mg/（kg·d） with intraperitoneal injection while those of control group received noradrenaline 12 mg/（kg·d） with intraperitoneal injection.30 minutes after injection,the blood pressure levels were measured with tail cuff blood pressure device to keep the general balance,and the entire procedure lasted for 14 d.14 d later,the arteriae aorta walls were taken to observe their structure through pathology.Meanwhile,the level of matrix metalloproteinase-9（MMP-9）,matrix metalloproteinase-2（MMP-2） and metalloprotease tissue inhibiting factor-2（TIMP-2） was tested by immunohistochemical method.Results Level of blood pressure in experimental group was（134.5±3.5）mmHg,versus（132.9±2.7）mmHg in control group,P0.05.Among 20 mice in experimental group,the tunica media of arteriae aorta walls of 12 mice were found thinner and some of them were broken.Also,7 mice were found with obvious aortic dissection versus no significant change in control group.The level of MMP-9,MMP-2 and TIMP-2 were 0.451 3±0.022 1,0.508 4±0.013 1,0.623 8±0.014 2 in experimental group,and 0.285 7±0.011 3,0.381 4±0.020 3,0.354 5±0.021 3 in control group,all P0.05.Conclusion Angiotensin Ⅱcan induced mice′s aortic dissection by increasing the level and activity of MMP-9,MMP-2 and lowering that of TIMP-2.