摘要
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 of AT2R were （78.80±41.26）%, （68.98±23.93）%, （68.13 ± 23.23）% and （70.15 ± 17.16）%, respectively. Conclusion Ang Ⅱ could induce ALI and downregulate AT2R mRNA expression in the lung of ALI rats, whereas losartan acts as a positive regulator. AT2R seems to present lung protection in ALI.
出处
《中国危重病急救医学》
CAS
CSCD
北大核心
2008年第10期585-587,I0002,共4页
Chinese Critical Care Medicine
基金
国家自然科学基金资助项目（30640012）
