血管紧张素(1-7)对血管紧张素Ⅱ诱导肝星状细胞表达结缔组织生长因子的抑制作用
혈관긴장소(1-7)대혈관긴장소Ⅱ유도간성상세포표체결체조직생장인자적억제작용
Angiotensin (1-7) inhibits angiotensin Ⅱ-stimulated expression of connective tissue growth factor mRNA in hepatic stellate cells
  • 万方数据
    中华肝脏病杂志 중화간장병잡지
    CHINESE JOURNAL OF HEPATOLOGY
    2012年 6期 458-462 ,共5页

    李旭%黄茂梁%黄珊%张文雍%宁佐伟%孟莹

    리욱%황무량%황산%장문옹%저좌위%맹형

    肝硬化%血管紧张素Ⅱ%肝星状细胞%血管紧张素(1-7)%结缔组织生长因子 肝硬化%血管緊張素Ⅱ%肝星狀細胞%血管緊張素(1-7)%結締組織生長因子
    간경화%혈관긴장소Ⅱ%간성상세포%혈관긴장소(1-7)%결체조직생장인자
    Liver cirrhosis%AngiotensinⅡ%Hepatic stellat cell%Angiotensin(1-7)%Connective tissue growth factor
    目的 探讨血管紧张素(Ang)(1-7)对Ang Ⅱ诱导的肝星状细胞(HSC)表达结缔组织生长因子(CTGF)的抑制作用及其机制.方法 培养人HSC细胞系(LX2细胞),以AngⅡ刺激24h,分别予以AngⅡl型受体阻断剂irbesartan、ROCK抑制剂Y27632预处理lh.设立AngⅡ+ Ang (1-7)处理组,观察Ang (1-7)对Ang Ⅱ的抑制作用；Mas受体拮抗剂A779阻断Mas受体,观察对Ang (1-7)抑制效应的阻断作用.利用Western blot、逆转录聚合酶链反应(RT-PCR)和多基因定量检测系统检测RhoA、ROCK2 mRNA、结缔组织生长因子(CTGF)蛋白和mRNA的表达.结果 研究结果显示Ang Ⅱ刺激后,RhoA蛋白(0.87±0.093对比0.337±0.074)、ROCK2mRNA (0.747±0.061对比0.163±0.024)、CTGF mRNA (0.578±0.028对比0.262±0.007)相对表达量与对照组相比显著增高,差异有统计学意义(P值均＜0.01);irbesartan (RhoA蛋白:0.558±0.030对比0.87±0.093 ; ROCK2 mRNA:0.368±0.023对比0.747±0.061 ; CTGFmRNA:0.309±0.019对比0.578±0.028).Y27632(RhoA蛋白:0.564±0.067对比0.87±0.093 ; ROCK2 mRNA:0.218±0.046对比0.747±0.061 ; CTGF mRNA:0.340±0.020对比0.578±0.028)预处理组上述基因或蛋白相对表达量显著减低,差异有统计学意义(P值均＜0.01);Ang (1-7)单独处理组RhoA蛋白(0.449±0.035对比0.337±0.074)及CTGF mRNA(0.256±0.008对比0.262±0.007)与对照组相比无明显改变,差异无统计学意义(P值均＞0.05)；但是Ang(1-7)可抑制AngⅡ诱导的上述基因或蛋白表达的增高(RhoA蛋白:0.615 ±0.034对比0.87±0.093;ROCK2 mRNA:0.403 ±0.040对比0.747±0.061; CTGF mRNA:0.265±0.011对比0.578±0.028),差异有统计学意义(P值均＜0.01); Mas受体拮抗剂A779可以阻断Ang (1-7)对AngⅡ的抑制作用(RhoA蛋白:0.929±0.076对比0.615±0.034; ROCK2 mRNA:0.720±0.054对比0.403±0.040; CTGF mRNA:0.568±0.029对比0.265±0.011),差异有统计学意义(P值均＜0.01).结论 AngⅡ通过RhoA-ROCK通路促进人HSC表达CTGF mRNA; Ang (1-7)与其Mas受体结合后对AngⅡ激活的CTGF mRNA的表达具有抑制作用.
    목적 탐토혈관긴장소(Ang)(1-7)대Ang Ⅱ유도적간성상세포(HSC)표체결체조직생장인자(CTGF)적억제작용급기궤제.방법 배양인HSC세포계(LX2세포),이AngⅡ자격24h,분별여이AngⅡl형수체조단제irbesartan、ROCK억제제Y27632예처리lh.설립AngⅡ+ Ang (1-7)처리조,관찰Ang (1-7)대Ang Ⅱ적억제작용；Mas수체길항제A779조단Mas수체,관찰대Ang (1-7)억제효응적조단작용.이용Western blot、역전록취합매련반응(RT-PCR)화다기인정량검측계통검측RhoA、ROCK2 mRNA、결체조직생장인자(CTGF)단백화mRNA적표체.결과 연구결과현시Ang Ⅱ자격후,RhoA단백(0.87±0.093대비0.337±0.074)、ROCK2mRNA (0.747±0.061대비0.163±0.024)、CTGF mRNA (0.578±0.028대비0.262±0.007)상대표체량여대조조상비현저증고,차이유통계학의의(P치균＜0.01);irbesartan (RhoA단백:0.558±0.030대비0.87±0.093 ; ROCK2 mRNA:0.368±0.023대비0.747±0.061 ; CTGFmRNA:0.309±0.019대비0.578±0.028).Y27632(RhoA단백:0.564±0.067대비0.87±0.093 ; ROCK2 mRNA:0.218±0.046대비0.747±0.061 ; CTGF mRNA:0.340±0.020대비0.578±0.028)예처리조상술기인혹단백상대표체량현저감저,차이유통계학의의(P치균＜0.01);Ang (1-7)단독처리조RhoA단백(0.449±0.035대비0.337±0.074)급CTGF mRNA(0.256±0.008대비0.262±0.007)여대조조상비무명현개변,차이무통계학의의(P치균＞0.05)；단시Ang(1-7)가억제AngⅡ유도적상술기인혹단백표체적증고(RhoA단백:0.615 ±0.034대비0.87±0.093;ROCK2 mRNA:0.403 ±0.040대비0.747±0.061; CTGF mRNA:0.265±0.011대비0.578±0.028),차이유통계학의의(P치균＜0.01); Mas수체길항제A779가이조단Ang (1-7)대AngⅡ적억제작용(RhoA단백:0.929±0.076대비0.615±0.034; ROCK2 mRNA:0.720±0.054대비0.403±0.040; CTGF mRNA:0.568±0.029대비0.265±0.011),차이유통계학의의(P치균＜0.01).결론 AngⅡ통과RhoA-ROCK통로촉진인HSC표체CTGF mRNA; Ang (1-7)여기Mas수체결합후대AngⅡ격활적CTGF mRNA적표체구유억제작용.
    Objective To explore the angiotensin peptide [Ang (1-7)]-mediated inhibition of Ang Ⅱ in human hepatic stellate cells (HSCs) and determine the involvement of the ACE2-Ang (1-7)-Mas axis.Methods The human HSC line,LX2,was used in all experiments,and divided into control (unstimulated)and Ang Ⅱ-stimulated (10-6 mol/L) groups.The Ang Ⅱ-stimulated cells were further divided among several pretreatment (prior to Ang Ⅱ) groups:ROCK-inhibited (Y27632 blocking agent,10-6mol/L); irbesartan-inhibited (AT-1 receptor antagonist,10-6mol/L); and Mas receptor-inhibited (A779 Mas receptor antagonist,10-6mol/L).To explore the potential inhibitory effects of various Ang family members,the Ang Ⅱ-stimulated and pre-treated LX2 cells were exposed to Ang (1-7) (10-6 mol/L) for 24h.Western blot,reverse transcription-polymerase chain reaction (RT-PCR),and QuantiGene assay were used to assess changes in protein and mRNA expression levels of RhoA,ROCK,and connective tissue growth factor (CTGF).Results Compared with the control group,Ang Ⅱ-stimulated cells showed significantly increased levels of RhoA protein (0.337±0.074 vs.0.870±0.093),ROCK2 mRNA (0.747±0.061 vs.0.368±0.023),and CTGF mRNA (0.262±0.007 vs.0.578±0.028) (all,P＜0.01).Pre-treatment with irbesartan 0r Y27632 eliminated these responses.Ang (1-7) inhibited the Ang Ⅱ-stimulated up-regulation of RhoA,ROCK,and CTGF.Conclusion Ang (1-7) can inhibit the Ang Ⅱ-stimulated up-regulation of RhoA,ROCK and CTGF in hepatic stellate cells,indicating that the ACE2-Ang (1-7)-Mas axis,an important branch of the renin-Ang-aldosterone system is involved in the occurrence and development of liver fibrosis.
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