替米沙坦与雷米普利对盐敏感性高血压大鼠胸主动脉平滑肌细胞p38丝裂原活化蛋白激酶及血管紧张素Ⅱ1型受体表达的抑制作用  

Inhibition effect of telmisartan and ramipril on the expressions of p38 mitogen-activated protein kinase and angiotensin Ⅱ type 1 receptor in thoracic aortic smooth muscle cells of salt-sensitive hypertensive rats

作　　者：姜黔峰[1,2] 杜银 焦阳 王怡文 何绘姗 

机构地区：[1]遵义市第一人民医院 [2]遵义医学院第三附属医院心血管内科,贵州遵义563000 [3]临沂市兰山区人民医院内一科,山东临沂276000

出　　处：《中国临床药理学杂志》2017年第19期1930-1933,共4页The Chinese Journal of Clinical Pharmacology

基　　金：遵义市创新人才团队基金资助项目(遵市科合[2016]6号);遵义市红花岗区科学技术基金资助项目(遵红科合[2012]012号)

摘　　要：目的探讨p38丝裂原活化蛋白激酶(p38MAPK)和血管紧张素Ⅱ1型受体(AT1R)在盐敏感性高血压大鼠胸主动脉平滑肌细胞的表达,及替米沙坦和雷米普利对其的干预效应。方法选取18只新生雄性Wistar大鼠第1,2天分别注射50 mg·kg^(-1)辣椒辣素,哺乳期(3周)后,给予高盐(4%Na Cl)喂食4周建立感觉神经损伤性盐敏感性高血压大鼠模型。将18只模型大鼠随机分成模型组、实验A组和实验B组,每组6只;另取6只空白大鼠作为对照组。对照组和模型组均予以等量0.9%Na Cl;实验A组予以替米沙坦10 mg·kg^(-1)·d^(-1),qd,灌胃给药;实验B组予以雷米普利1 mg·kg^(-1)·d^(-1),qd,灌胃给药。4组大鼠均干预4周。取4组大鼠胸主动脉平滑肌细胞培养,收集第4~6代细胞。用实时荧光聚合酶链式反应检测p38MAPK和AT1R mRNA的表达,用Western-blot法检测磷酸化p38MAPK(p-p38MAPK)和AT1R蛋白的表达。结果对照组、模型组、实验A组和实验B组的p38MAPK mRNA分别为(100.00±21.82),(181.56±5.00),(125.78±12.64)和(131.90±6.61),AT1R mRNA分别为(100.00±11.87),(270.98±17.68),(80.60±9.40)和(228.04±9.77),p38MAPK蛋白表达分别为(0.21±0.05),(0.76±0.22),(0.39±0.14)和(0.45±0.03),AT1R蛋白表达分别为(0.31±0.09),(1.57±0.41),(0.87±0.14)和(0.97±0.18),对照组、实验A,B组的上述指标与模型组比较,差异均有统计学意义(均P<0.05)。结论替米沙坦和雷米普利能够抑制p38MAPK和AT1R在盐敏感性高血压大鼠胸主动脉平滑肌细胞的表达。Objective To investigate the expressions of p38 mitogen-activated protein kinase（ p38MAPK） and angiotensin Ⅱ type 1 receptor（ AT1R） in artery smooth muscle cells of salt-sensitive hypertention rats as well as the effect of telmisartan and ramipril intervention. Methods Eighteen newborn male Wistar rats were given 50 mg · kg^-1 capsaicin subcutaneously on the first and second day of life,after the weaning（ 3weeks of life）,the rats were fed on high sodium diet（ 4% Na Cl） for 4weeks to establish the salt-sensitive hypertension model induced by sensory denervation. The rats were divided into three groups includingmodel group,test A group and test B group,with 6 rats in each group. Another six aged-matched rats were served as control group. Control group and model group were given equivalent physiological saline,test A group was lavaged with telmisartan（ 10 mg·kg^-1·d^-1）,test B group was lavaged with ramipril（ 1 mg·kg^-1·d^-1）. Four groups of rats were treated for 4 weeks. Primary culture of aortic smooth muscle cell from four groups was established in vitro,aortic smooth muscle cells at the 4-6th passage were used in the following experiments. The expressions of p38 MAPK and AT1 R mRNA were determined by reverse transcription polymerase chain reaction. The phosphorylated p38MAPK（ p-p38MAPK） and AT1 R protein were measured by Western-blot. Results The expressions of p38 MAPK mRNA in control group, model group, test A group and test B group were（ 100 ± 21. 82）,（ 181. 56 ± 5. 00）,（ 125. 78 ± 12. 64） and（ 131. 90 ± 6. 61）,respectively,the expressions of AT1 R mRNA were（ 100 ± 11. 87）,（ 270. 98 ± 17. 68）,（ 80. 60 ± 9. 40） and（ 228. 04 ± 9. 77）, the protein expression of p38 MAPK were（ 0. 21 ± 0. 05）,（ 0. 76 ± 0. 22）,（ 0. 39 ± 0. 14） and（ 0. 45 ± 0. 03）,the protein expressions of AT1 R were（ 0. 31 ± 0. 09）,（ 1. 57 ± 0. 41）,（ 0. 87 ± 0. 14） and（ 0. 97 ± 0. 18）. Compared with the model group,the expressions in

关 键 词：替米沙坦 雷米普利 盐敏感 高血压 P38丝裂原活化蛋白激酶 血管紧张素Ⅱ1型受体 

分 类 号：R972.4[医药卫生—药品]