AngⅡ促进成年大鼠心脏成纤维细胞periostin表达的信号通路研究  

EFFECT OF ANGIOTENSINⅡON PERIOSTIN MRNA EXPRESSION AND ITS RELATED SIGNAL MECHANISM IN ADULT RAT CARDIAC FIBROBLASTS

作　　者：邹平[1,2] 吴丹[1] 吴立玲[1] 李丽[1] 

机构地区：[1]北京大学医学部生理学与病理生理学系和教育部分子心血管病重点实验室,北京100191 [2]泸州医学院病理生理学教研室

出　　处：《现代预防医学》2011年第16期3265-3269,3272,共6页Modern Preventive Medicine

基　　金：国家自然科学基金 (30800372; 30871014);国家重点基础研究发展计划 (973) (2007CB512004)

摘　　要：[目的]观察血管紧张素II对心脏成纤维细胞periostin mRNA表达的影响及其相关信号转导机制。[方法]在离体培养的成年大鼠心脏成纤维细胞,RT-PCR检测periostin的mRNA表达,荧光法检测细胞内活性氧含量。[结果]10-7～10-5mol/L血管紧张素II刺激6h使periostin的mRNA表达分别增加了1.1倍、2.5倍和2.3倍。10-6mol/L血管紧张素II刺激3～24h均可显著增加periostinm RNA表达,其中以6h作用最为显著。血管紧张素1型受体阻断剂洛沙坦及蛋白激酶C抑制剂白屈菜红碱显著抑制了血管紧张素II诱导的periostinmRNA表达增加。血管紧张素II刺激30min可显著增加心脏成纤维细胞内活性氧的产生,白屈菜红碱可减少血管紧张素II诱导的活性氧生成增加。活性氧清除剂N-乙酰-L-半胱氨酸或c-Jun氨基末端激酶抑制剂SP600125预孵育明显抑制了血管紧张素II诱导的periostin蛋白表达增加。[结论]血管紧张素II可促进periostin的mRNA表达,蛋白激酶C/活性氧/c-Jun氨基末端激酶途径参与了血管紧张素II对periostin表达的上调作用。[Objective]To investigate the effects of angiotensin Ⅱ（Ang Ⅱ）on periostin mRNA expression in adult rat cardiac fibroblasts and its related signal transduction pathway.[Methods]Adult rat cardiac fibroblasts were cultured. The mRNA and protein expressions of periosotin were detected by using RT-PCR and Western blot,respectively. Intracellular reactive oxygen species（ROS）production was measured using 2,7-dichlorofluorescein diacetate（DCF-DA）,an oxidant-sensitive fluorescent probe.[Results]The mRNA expression of periostin in adult rat cardiac fibroblasts were increased by 1.1 times,2.5 times and 2.3 times,respectively,when cells were treated with 10-7-10-5 mol/L AngII for 6 h. Stimulation with 10-6 mol/L AngII for 3-24 h enhanced periostin mRNA expression and a maximal effect was achieved at 6 h. The periostin mRNA level was decreased significantly when pretreated with losartan,an AT1 receptor blocker,or chelerythrine,a protein kinase C（PKC）inhibitor. AngII induced the production of ROS in cardiac fibroblasts,which was abolished by PKC inhibition. Incubation cells with N-acetylcysteine（NAC）,a ROS scavenger or SP600125,a specific c-jun N-terminal protein kinase（JNK）inhibitor,significantly decreased periostin expression induced by AngII.[Conclusion]The PKC/ROS/JNK pathway was involved in the stimulatory effect of AngII on periostin expression in aCFs.

关 键 词：血管紧张素Ⅱ 心脏成纤维细胞 PERIOSTIN 信号通路 

分 类 号：R541[医药卫生—心血管疾病]