缬沙坦对主动脉球囊损伤大鼠主动脉内膜SRSF1表达的影响  

EFFECT OF VALSARTAN ON THE EXPRESSION OF SERINE/ARGININE-RICH SPLICING FACTOR-1 IN THE AORTIC INTIMA OF RATS WITH AORTIC BALLOON INJURY

作　　者：彭亮 段硕 李永红[1] 徐辉[1] 杨茜[1] 唐锡龙 PENG Liang;DUAN Shuo;LI Yonghong;XU Hui;YANG Xi;TANG Xilong(Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China)

机构地区：[1]青岛大学医学院附属医院心内科,山东青岛266003 [2]平邑县人民医院急诊科 [3]武汉亚洲心脏病医院心内科

出　　处：《精准医学杂志》2020年第6期505-509,共5页Journal of Precision Medicine

基　　金：山东省重点研发计划项目(2018GSF118241)。

摘　　要：目的通过观察缬沙坦对主动脉球囊损伤模型大鼠主动脉血管内膜丝氨酸/精氨酸富集剪接因子1(SRSF1)表达的影响,探讨缬沙坦在预防血管再狭窄中的作用机制。方法选取健康雄性Wistar大鼠48只,随机分为对照组、手术组和缬沙坦组,每组各16只大鼠。从术前第1天至术后第14天(或第28天),每天分别给予手术组和对照组大鼠5 mL蒸馏水灌胃,缬沙坦组大鼠每天将20 mg/kg缬沙坦溶于5 mL蒸馏水中灌胃。麻醉后,手术组和缬沙坦组大鼠使用自制的2F球囊导管建立主动脉球囊损伤模型,对照组大鼠操作同手术组,但未注水扩张球囊。各组分别于术后第14天和28天分别处死8只大鼠,分别收集近主动脉弓血管5 mm,进行组织形态学观察并测定内膜增生情况;采用实时荧光定量PCR和免疫荧光法分别检测血管组织中SRSF1 mRNA及蛋白的表达情况。结果对照组大鼠主动脉球囊损伤术后第14天和第28天时血管内膜光滑,均无明显损伤及斑块形成,而手术组和缬沙坦组血管内均可见新生内膜增生,创面均有不同程度的内皮细胞覆盖,内弹力膜部分断裂。重复测量设计的方差分析结果显示,组别、时间、时间与组别(交互作用)对大鼠主动脉血管内膜厚度、SRSF1 mRNA相对表达量均有明显的影响(F组别=372.90、184.60,F时间=26.13、21.15,F交互=12.31、4.22,P<0.05)。与对照组相比,术后第14、28天手术组与缬沙坦组内膜厚度、内膜SRSF1 mRNA相对表达量均明显增加,缬沙坦组较手术组明显降低(F=23.18~241.08,P<0.05)。术后第14、28天对照组血管组织中SRSF1蛋白荧光强度极低,手术组和缬沙坦组SRSF1蛋白荧光强度均显著高于对照组,缬沙坦组明显低于手术组。与术后第14天相比,术后第28天手术组、缬沙坦组血管组织中SRSF1蛋白荧光强度均明显增加。结论缬沙坦可有效减轻内膜损伤血管的内膜增生程度,其作用机制可能与其下调血管组织Objective\To investigate the effect of valsartan on the expression of serine/arginine-rich splicing factor-1(SRSF1)in the aortic intima in a rat model of aortic balloon injury,as well as the mechanism of action of valsartan in preventing vascular restenosis.\Methods\A total of 48 healthy male Wistar rats were randomly divided into control group,operation group,and valsartan group,with 16 rats in each group.From day 1 before surgery to day 14(or 28)after surgery,the rats in the operation group and the control group were given 5 mL distilled water daily by gavage,while those in the valsartan group were given valsartan(20 mg/kg)dissolved in 5 mL distilled water daily by gavage.After anesthesia,the rats in the operation group and the valsartan group were treated with a self-made 2F balloon catheter to establish a rat model of aortic balloon injury,and those in the control group were given the same surgery without water injection to dilate the balloon.For each group,8 rats each were sacrificed on days 14 and 28 after surgery,and 5 mm blood vessels were collected near the aortic arch to observe histological changes and measure intimal hyperplasia.Quantitative real-time PCR and immunofluorescence assay were used to measure the mRNA and protein expression of SRSF1 in vascular tissue.\Results\On days 14 and 28 after aortic balloon injury,the control group had smooth intima without obvious injury and plaque formation,while the operation group and the valsartan group had neointimal hyperplasia,wound surface with varying degrees of endothelial cell coverage,and partial rupture of the internal elastic membrane.The repeated measures analysis of variance showed that group,time,and time-group interaction had significant effects on aortic intimal thickness(Fgroup=372.90,Ftime=26.13,Finteraction=12.31,P<0.05)and relative mRNA expression of SRSF1(Fgroup=184.60,Ftime=21.15,Finteraction=4.22,P<0.05).Compared with the control group on days 14 and 28 after surgery,the operation group and the valsartan group had significant increases in

关 键 词：缬沙坦 丝氯酸-精氨酸剪接因子 血管内膜 创伤和损伤 肌细胞 平滑肌 细胞增殖 疾病模型 动物 大鼠 WISTAR 

分 类 号：R543[医药卫生—心血管疾病] R972.4[医药卫生—内科学]