摘要
目的：研究血管紧张素对心肌细胞 Ｂｃｌ┐２ 和 ｃ┐ｍｙｃ 基因转录的调控作用及其受体机制。 方法：分离纯化培养的乳鼠心肌细胞，分别加入血管紧张素或／和氯沙坦（血管紧张素的 Ｉ型受体特异性拮抗剂）处理，然后提取总 Ｒ Ｎ Ａ，用 Ｎｏｒｔｈｅｒｎ 杂交检测 Ｂｃｌ┐２ 和 ｃ┐ｍｙｃ 基因的转录水平。结果分析时，以正常乳鼠心肌细胞中 Ｂｃｌ┐２ ｍ Ｒ Ｎ Ａ ／ １８ Ｓ或 ｃ┐ｍｙｃｍ Ｒ Ｎ Ａ ／ １８ Ｓ的比值定为 １００ ％ 。结果：血管紧张素 １０－ ５ ｍ ｏｌ· Ｌ－ １ 处理 ２４ 小时使 Ｂｃｌ┐２ 基因转录水平下调至正常的２６ ％ （ Ｐ＜ ０．０１， ｎ＝ ３ ）。血管紧张素的处理时间短至 １２ 小时或血管紧张素浓度为 １０－ ７ ｍ ｏｌ· Ｌ－ １ 或 １０－ ６ ｍ ｏｌ· Ｌ－ １ 时均无此作用，表明血管紧张素使心肌细胞 Ｂｃｌ┐２ 基因转录下调具有时间和剂量依赖性。氯沙坦 １０－ ５ ｍ ｏｌ· Ｌ－ １能完全取消 １０－ ５ ｍ ｏｌ· Ｌ－ １ 血管紧张素对心肌细胞 Ｂｃｌ┐２ 基因转录下调的作用（１０３±４ ％ ， Ｐ＜ ０．０１， ｎ＝ ３ ），单独用 １０－ ６ ｍ ｏｌ· Ｌ－ １ 或 １０－ ５ ｍ ｏｌ· Ｌ－ １
\ Aim:To investigate the effects of angiotensin Ⅱ(Ang Ⅱ) on the regulation of Bcl 2 and c myc genes transcription in cardiac myocytes and its receptor mechanism.\ Methods:The cultured neonatal rat cardiac myocytes were treated with Ang Ⅱ and losartan (a specific antagonist of AT 1 receptor). Then total RNA was isolated, the level of Bcl 2 and c myc mRNA was detected by Northern blot. The ratio of Bcl 2 mRNA/18S and c myc mRNA/18S in control group was set to 100 %.\ Results:Incubation of cultured neonatal rat cardiac myocytes with 10 5 mol·L -1 Ang Ⅱ for 24 hours elicited the down regulation of Bcl 2 gene transcription to 26 % of control ( P< 0.01, n= 3 ), whereas the above down regulation change was not observed with a treatment period shorter than 12 hours or at a dose lower than 10 -6 mol·L -1 Ang Ⅱ. Losartan (10 -6 mol·L -1 and 10 -5 mol·L -1 ) had no direct effects on the regulation of Bcl 2 gene transcription in cardiac myocytes, but it can suppress the down regulation induced by Ang Ⅱ (10 -5 mol·L -1 ). After the treatment of cultured neonatal rat cardiac myocytes with 10 -5 mol·L -1 Ang Ⅱ for 2 h, the transcription of c myc gene was up regulated by 340 ± 70 %, P< 0.01, n= 3. This effect can be abolished by 10 -5 mol·L -1 losartan (120 ± 20 % vs 340 ± 70 %, P< 0.01, n= 3 ).\ Conclusion: The results indicate that the down regulation of the Bcl 2 gene transcription and enhancement of c myc gene transcription by AngⅡ were mainly mediated by AT 1 receptor.
出处
《高血压杂志》
CSCD
1999年第3期272-275,共4页
Chinese Journal of Hypertension
关键词
血管紧张素Ⅱ
心肌细胞
BCL-2基因
转录调控
ywords\ ::angiotensinⅡ
\ cardiac myocytes
\ rat
\ Bcl 2 gene
\ c myc gene
\ transcription regulation
\ losartan
