中国危重病急救医学
中國危重病急救醫學
중국위중병급구의학
CHINESE CRITICAL CARE MEDICINE
2008年
4期
218-222
,共5页
王立军%马虹%廖新学%何建桂%张文武%田方%蔡乙明%顾海波%郝艳华%胡雪松%邹红梅%周秋玲
王立軍%馬虹%廖新學%何建桂%張文武%田方%蔡乙明%顧海波%郝豔華%鬍雪鬆%鄒紅梅%週鞦玲
왕립군%마홍%료신학%하건계%장문무%전방%채을명%고해파%학염화%호설송%추홍매%주추령
血管紧张素转换酶-2%替米沙坦%肾素-血管紧张素系统%高血压%主动脉缩窄
血管緊張素轉換酶-2%替米沙坦%腎素-血管緊張素繫統%高血壓%主動脈縮窄
혈관긴장소전환매-2%체미사탄%신소-혈관긴장소계통%고혈압%주동맥축착
angiotensin-converting enzyme 2%telmisartan%renin-angiotensin system%hyperten sion%suprarenal aortic coarctation
目的 探讨血管紧张素转换酶-2(ACE2)在压力超负荷大鼠心肌中的表达,以及替米沙坦对其表达的影响.方法 将8周龄雄性SD大鼠60只随机分为假手术组、模型组和替米沙坦低、高剂量治疗组.制备腹主动脉缩窄动物模型.替米沙坦高、低剂量组大鼠术前1 d开始分别给予替米沙坦10 mg·kg-1 ·d-1和2 mg·kg-1·d-1管饲,假手术组和模型组则饲以等量生理盐水,每日1次,持续3周.3周后留取血浆和心肌组织标本,以放射免疫法检测血浆和心肌血管紧张素Ⅱ(Ang Ⅱ)浓度;以逆转录-聚合酶链反应(RT-PCR)检测心肌中ACE2和ACE的mRNA表达;以蛋白质免疫印迹法(Western blotting)检测其蛋白表达.结果 与假手术组比较,模型组血浆及心肌中Ang Ⅱ浓度明显增高(血浆(495.1±55.6)ng/L比(269.2±39.5)ng/L,心肌(103.6±23.7)ng/g比(49.5±13.5)ng/g,P均＜0.01],用替米沙坦干预可升高其水平(P均＜0.05),高剂量组显著高于低剂量组[血浆(702.2±40.6)ng/L比(612.6±35.5)ng/L,心肌(211.5±21.5)ng/g比(189.6±43.6)ng/g,P均＜0.053.模型组心肌ACE2蛋白及基因表达均增加(蛋白1.164±0.06比0.79±0.04,基因0.54±0.08比0.41±0.04,P均＜0.05).与模型组比较,替米沙坦干预使心肌ACE2表达增加,呈剂量依赖性,其中低、高剂量组ACE2蛋白表达分别增高1.0倍、1.6倍,基因表达分别增高1.3倍、1.6倍(P均＜0.05).模型组ACE蛋白及基因表达显著增加(蛋白2.10±1.07比1.02±0.05,基因1.93±0.09比0.26±0.09,P均＜0.01),替米沙坦对其表达无显著影响(P均＞0.05).结论 腹主动脉缩窄可显著上调心肌ACE和ACE2的蛋白及基因表达;替米沙坦可能通过上调其水平来发挥治疗作用.
目的 探討血管緊張素轉換酶-2(ACE2)在壓力超負荷大鼠心肌中的錶達,以及替米沙坦對其錶達的影響.方法 將8週齡雄性SD大鼠60隻隨機分為假手術組、模型組和替米沙坦低、高劑量治療組.製備腹主動脈縮窄動物模型.替米沙坦高、低劑量組大鼠術前1 d開始分彆給予替米沙坦10 mg·kg-1 ·d-1和2 mg·kg-1·d-1管飼,假手術組和模型組則飼以等量生理鹽水,每日1次,持續3週.3週後留取血漿和心肌組織標本,以放射免疫法檢測血漿和心肌血管緊張素Ⅱ(Ang Ⅱ)濃度;以逆轉錄-聚閤酶鏈反應(RT-PCR)檢測心肌中ACE2和ACE的mRNA錶達;以蛋白質免疫印跡法(Western blotting)檢測其蛋白錶達.結果 與假手術組比較,模型組血漿及心肌中Ang Ⅱ濃度明顯增高(血漿(495.1±55.6)ng/L比(269.2±39.5)ng/L,心肌(103.6±23.7)ng/g比(49.5±13.5)ng/g,P均＜0.01],用替米沙坦榦預可升高其水平(P均＜0.05),高劑量組顯著高于低劑量組[血漿(702.2±40.6)ng/L比(612.6±35.5)ng/L,心肌(211.5±21.5)ng/g比(189.6±43.6)ng/g,P均＜0.053.模型組心肌ACE2蛋白及基因錶達均增加(蛋白1.164±0.06比0.79±0.04,基因0.54±0.08比0.41±0.04,P均＜0.05).與模型組比較,替米沙坦榦預使心肌ACE2錶達增加,呈劑量依賴性,其中低、高劑量組ACE2蛋白錶達分彆增高1.0倍、1.6倍,基因錶達分彆增高1.3倍、1.6倍(P均＜0.05).模型組ACE蛋白及基因錶達顯著增加(蛋白2.10±1.07比1.02±0.05,基因1.93±0.09比0.26±0.09,P均＜0.01),替米沙坦對其錶達無顯著影響(P均＞0.05).結論 腹主動脈縮窄可顯著上調心肌ACE和ACE2的蛋白及基因錶達;替米沙坦可能通過上調其水平來髮揮治療作用.
목적 탐토혈관긴장소전환매-2(ACE2)재압력초부하대서심기중적표체,이급체미사탄대기표체적영향.방법 장8주령웅성SD대서60지수궤분위가수술조、모형조화체미사탄저、고제량치료조.제비복주동맥축착동물모형.체미사탄고、저제량조대서술전1 d개시분별급여체미사탄10 mg·kg-1 ·d-1화2 mg·kg-1·d-1관사,가수술조화모형조칙사이등량생리염수,매일1차,지속3주.3주후류취혈장화심기조직표본,이방사면역법검측혈장화심기혈관긴장소Ⅱ(Ang Ⅱ)농도;이역전록-취합매련반응(RT-PCR)검측심기중ACE2화ACE적mRNA표체;이단백질면역인적법(Western blotting)검측기단백표체.결과 여가수술조비교,모형조혈장급심기중Ang Ⅱ농도명현증고(혈장(495.1±55.6)ng/L비(269.2±39.5)ng/L,심기(103.6±23.7)ng/g비(49.5±13.5)ng/g,P균＜0.01],용체미사탄간예가승고기수평(P균＜0.05),고제량조현저고우저제량조[혈장(702.2±40.6)ng/L비(612.6±35.5)ng/L,심기(211.5±21.5)ng/g비(189.6±43.6)ng/g,P균＜0.053.모형조심기ACE2단백급기인표체균증가(단백1.164±0.06비0.79±0.04,기인0.54±0.08비0.41±0.04,P균＜0.05).여모형조비교,체미사탄간예사심기ACE2표체증가,정제량의뢰성,기중저、고제량조ACE2단백표체분별증고1.0배、1.6배,기인표체분별증고1.3배、1.6배(P균＜0.05).모형조ACE단백급기인표체현저증가(단백2.10±1.07비1.02±0.05,기인1.93±0.09비0.26±0.09,P균＜0.01),체미사탄대기표체무현저영향(P균＞0.05).결론 복주동맥축착가현저상조심기ACE화ACE2적단백급기인표체;체미사탄가능통과상조기수평래발휘치료작용.
Objective To study the effect of hypertension and telmisartan treatment on the protein and gene expression of cardiac angiotensin-converting enzyme 2(ACE2)in pressure-overloaded rats.Methods Coarctation of suprarenal abdominal aorta was reproduced in 8 week-old male Sprague-Dawley(SD)rats and then randomized into 4 groups,including a sham group(n=15),a suprarenal aortic coarctation group (model group,n=12),a suprarenal aortic coarctation with low-dose Telmisartan treatment group(low-dose gavaged 24 hours before the operation and once every day afterwards for 3 weeks.At the end of 3 weeks,the concentrations of angiotensin(Ang Ⅱ)in plasma and myocardium were measured by radioimmunoassay.Changes in both protein quantity and gene expressions of both ACE2 and ACE were determined by Western blotting analysis and reverse transcription-polymerase chain reaction(RT-PCR)technique,respectively.Results Suprarenal abdominal aortic coarctation induced a significant increase in the plasma and myocardium Ang Ⅱ concentration[plasma:(495.1±55.6)ng/L vs.(269.2±39.5)ng/L,myocardium:(103.6±23.7)ng/g vs.(49.5±13.5)ng/g,both P＜0.01] and expressions of gene and protein of ACE(P＜0.01)and ACE2(P＜0.05).Telmisartan further increased the concentration of Ang Ⅱ in plasma and myocardium in a dose-dependent manner(plasma:(702.2±40.6)ng/L vs.(612.6±35.5)ng/L,myoeardium(211.5±21.5)ng/g vs.(189.6±43.6)ng/g,both P＜0.05＝,and induced a dose-dependent increase in both protein and gene expression of ACE2(protein 1.16±0.06 vs.0.79±0.04,gene 0.54±0.08 vs.0.41±0.04,both P＜0.05＝.Expression of ACE2 protein in low-dose and high-dose groups was increased by 1.0 and 1.58 folds respectively,and gene was increased by 1.3 and 1.6 folds(all P＜0.05＝.The expression of ACE protein and gene in model group increased significantly(protein:2.10±1.07 vs.1.02±0.05,gene:1.93±0.09 vs.0.26±0.09,both P＜0.01＝.Telmisartan had no significant effect on ACE gene and protein expressions(both P＞0.05).Conclusion Suprarenal abdominal aortic coarctation induced a significant increases of ACE and ACE2 gene and protein expressions.Telmisartan induces a dose-dependent increases of cardiac ACE2 gene and protein expression,which may be the mechanism of its therapeutic effects.
