HIP-55介导血管紧张素Ⅱ诱导的血管胶原沉积

摘要

目的 探究HIP-55是否介导血管紧张素Ⅱ诱导的血管胶原沉积. 方法 生物信息学分析的方法预测HIP-55是否参与血管紧张素Ⅱ( AngⅡ)诱导的血管重构,小鼠背部皮下埋入AngⅡ(1 mg·kg-1·d-1 )微量泵14 d诱导血管重构模型,利用无创血压仪检测小鼠血压变化,蛋白质印迹法(Western blot)、反转录聚合酶链式反应( RT-PCR)检测HIP-55 在血管重构模型中的表达变化情况.并构建HIP-55基因敲除小鼠,将小鼠分为4组:野生/假手术组( WT/Sham组)、HIP-55基因敲除/假手术组(HIP-55-/-/Sham组)、野生/埋泵组(WT/AngⅡ组)和HIP-55基因敲除/埋泵组(HIP-55-/-/AngⅡ组),主动脉苏木素-伊红(HE)染色,Masson染色检测血管形态变化及胶原沉积变化. 结果 生物信息学提示HIP-55可能参与AngⅡ诱导的血管重构.与对照组相比,实验组小鼠血管胶原沉积显著增加(3. 1 ± 0. 18比1. 1 ± 0. 04,P<0. 01)、血管横切平均面积显著增加(2. 7 ± 0. 1比1. 0 ± 0. 04, P<0. 01)、平均厚度明显增加[(105. 7 ± 7. 0)μm 比 (66. 0 ± 7. 6)μm,P<0. 01]、平均厚度/内径明显增加(0. 28 ± 0. 01比0. 17 ± 0. 01, P<0. 01).实验组小鼠血管中HIP-55 mRNA(1. 6 ± 0. 22比1. 0 ± 0. 03,P<0. 01)和HIP-55 蛋白(1. 6 ± 0. 15 比1. 0 ± 0. 04,P<0. 01)表达水平均明显增加.与WT/Sham组相比,HIP-55-/-/Sham组小鼠的血管胶原沉积水平无明显变化(1. 1 ± 0. 04比1. 0 ± 0. 05,P=0. 70);给予AngⅡ埋泵后,与WT/Ang Ⅱ组相比,HIP-55-/-/Ang Ⅱ组小鼠的血管胶原沉积明显减少(2. 6 ± 0. 2比3. 3 ± 0. 1,P<0. 05). 结论 HIP-55介导Ang Ⅱ诱导的血管胶原沉积.%Objective To investigate whether HIP-55 mediates angiotensin Ⅱ-induced vascular collagen deposition. Methods Using bioinformatics analysis method predicted whether HIP-55 was involved in angiotensin Ⅱ-induced vascular remodeling; an angiotensin Ⅱ (1 mg·kg-1·d-1 ) micropump was implanted subcutaneously in the back of the mouse for 14 days to induce a vascular remodeling model. The blood pressure changes of the mice were detected by non-invasive blood pressure meter, RT-PCR and Western blot were used to detect the expression of HIP-55 in vascular remodeling model. HIP-55 knockout mouse were constructed and all the mouse were divided into 4 groups: wild/sham operation group ( WT/Sham group), HIP-55 gene knockout/sham operation group (HIP-55-/-/Sham group), wild/buried pump group (WT/Ang Ⅱ group) and HIP-55 gene knockout/buried pump ( HIP-55-/-/Ang Ⅱ group) . Using aortic HE staining and Masson staining methods, the changes of vascular morphology and collagen deposition were detected. Results Bioinformatics suggested that HIP-55 might be involved in angiotensinⅡ-induced vascular remodeling. The expression of vascular HIP-55 was significantly increased in angiotensinⅡ-induced vascular remodeling model (1. 6 ± 0. 15 vs. 1. 0 ± 0. 04, P <0. 01 ); The knockout of HIP-55 inhibited angiotensin Ⅱ-induced vascular collagen deposition (2. 6 ± 0. 2 vs. 3. 3 ± 0. 1, P<0. 05). Conclusions HIP-55 mediates angiotensin Ⅱ-induced vascular collagen deposition.