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