血管紧张素Ⅳ型受体过表达对早期动脉粥样硬化斑块形成的影响

Effects of the overexpression of type 4 angiotensin receptor on the formation of atherosclerotic lesions

目的探讨血管紧张素Ⅳ型受体(AT4R)过表达对早期动脉粥样硬化斑块形成的影响及可能机制。方法Apo E-/-小鼠60只高脂饮食喂养4周后,随机分为AT4R过表达组(Ad-AT4R组)、空载体组(Ad-EGFP组)和PBS空白对照组,每组20只。分别通过尾静脉注射携带有AT4R的腺病毒、腺病毒空载体及PBS溶液。继续高脂饮食4周后处死小鼠,留取血样及血管组织。检测血糖及血脂各项指标;采用苏木精-伊红染色法及油红O染色检测主动脉根部斑块面积百分比。结果与空白对照组和Ad-EGFP组相比,Ad-AT4R组体质量、血糖及血脂无显著性差异(P>0.05),苏木精-伊红染色及油红O染色斑块面积百分比显著降低(P<0.05)。结论 AT4R过表达可抑制早期动脉粥样硬化斑块的形成,且不依赖于对血糖、血脂水平的调节。因此,AT4R可能存在潜在抗动脉粥样硬化的作用。

Objective To explore the effects of type 4 angiotensin receptor（ AT4R） on the formation of atherosclerotic lesions and to elaborate the possible mechanism. Methods A total of 60 apolipoprotein E-deficient mice fed with highfat diet for 4 weeks were randomly divided into 3 groups： control group（ receiving infusion of PBS）,Ad-EGFP group（ receiving infusion of adenoviral vectors with green fluorescence protein） and Ad-AT4 R group（ receiving infusion of adenoviral vectors with AT4R）. High-fat diet lasted for another 4 weeks and then all mice were sacrificed to collect blood samples and whole aorta. The levels of blood glucose and blood lipid were measured. The aortic plaques were stained by HE and oil red O staining method to measure the percentage of positive atherosclerotic lesion area. Results There was no significant difference in blood glucose and serum lipid levels among the 3 groups. However,compared to the control group and the Ad-EGFP group,the Ad-AT4 R group showed lower positive atherosclerotic lesion area stained by HE and oil red（ P〈0. 05）. Conclusion Overexpression of AT4 R may inhibit the formation of atherosclerotic lesions independent of regulation of blood glucose and serum lipid. Thus AT4 R may provide protection against atherosclerosis.