目的探讨静脉注射血管紧张素Ⅱ(AngⅡ)和血管紧张素Ⅱ1型受体(AT1R)阻断药氯沙坦对大鼠肺组织AT2R表达的影响及AT2R与急性肺损伤(ALI)的相关性。方法24只SD大鼠被随机分为4组,每组6只。正常对照组和AngⅡ组:持续皮下注射生理盐水或AngⅡ1μg·kg^-1·min^-1 72h;AngⅡ+氯沙坦组:注射AngⅡ前24h及注射过程中给予氯沙坦10mg·kg^-1·d^-1灌胃,连用4d;氯沙坦组:仅用氯沙坦10mg·kg^-1·d^-1灌胃,连用4d。给药后活杀大鼠,分别用逆转录-聚合酶链反应(RT—PCR)和蛋白质免疫印迹法(Western blotting)检测肺组织AT2R的mRNA和蛋白表达,并行组织损伤病理评分。结果AngⅡ组肺组织病理评分[(3.33±1.14)分]明显高于正常对照组[(0.73±0.09)分];AngⅡ+氯沙坦组评分降至(1.98±0.30)分,而氯沙坦组为(0.95±0.20)分,各组间比较差异均有统计学意义(P〈0.05或P〈0.01)。AngⅡ组AT2R mRNA表达[(47.90±9.88)%]明显低于正常对照组[(86.33±5.90)%];AngⅡ+氯沙坦组AT2R mRNA表达上调[(90.63±19.66)%],而氯沙坦组为(68.65±4.88)%,各组间比较差异均有统计学意义(P〈0.05或P〈0.01)。正常对照组肺组织AT2R蛋白表达为(78.80±41.26)%,AngⅡ组为(68.98±23.93)%,AngⅡ+氯沙坦组为(68.13±23.23)%,氯沙坦组为(70.15±17.16)%,各组间比较差异均无统计学意义。结论AngⅡ可以诱导大鼠ALI并下调AT2R mRNA在肺组织中的表达,此时应用氯沙坦可上调AT2R mRNA表达,改善肺损伤;AT2R可能在ALI中发挥肺保护作用。
Objective To study the effect of angiotensin Ⅱ (Ang Ⅱ ) and losartan, which is an angiotensin Ⅱ type 1 receptor (ATIR) antagonist, on expression of AT2R in rat lung and the relationship between AT2R with acute lung injury (ALI). Methods Twenty-four Sprague-Dawley (SD) rats were randomly divided into normal group, Ang Ⅱ group, Ang Ⅱ +losartan group and losartan group, with 6 rats in each group. Normal group and Ang Ⅱ group were treated with continuous subcutaneous injection of normal saline (NS, 1 μg · kg^-1 · min^-1) or Ang Ⅱ (1 μg · kg^-1 · min^-1) for 72 hours respectively. Ang Ⅱ +losartan group was gavaged with losartan (10 mg· kg^-1 · d^-1) 24 hours before and during the 72 hours' continuous subcutaneous injection of Ang Ⅱ for a duration of 4 days. In losartan group rats were gavaged with losartan (10 mg · kg^-1 · d^-1) for 4 days only. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were employed to measure AT2R mRNA and protein. The pathology of the rat pulmonary was scored. Results Smith's score of pathology in Ang Ⅱ group [(3.33± 1.14) scores] was significantly higher than that of the normal group [(0. 73±0.09) score ], while it was significantly lower in Ang Ⅱ + losartan group [(1.98± 0.30) scores] than that of Ang Ⅱ group. Smith's score of pathology in losartan group was [(0.95 ± 0.20) scores]. The differences among four groups showed significant statistical difference (P〈0.05 or P〈0.01). AT2R mRNA in Ang Ⅱ group [(47.90±9.88)%] was significantly lower than that of normal group [(86.33±5.90)%], while it was significantly higher in Ang Ⅱ +losartan group [(90.63 ± 19.66)%] than Ang Ⅱ group. AT2R mRNA of losartan group was (68.65±4.88)%. The differences among four groups had significant statistical difference (P〈0.05 or P〈0. 01). While on protein level showed no statistically significant difference among the four groups. The values o