中国临床药理学杂志
中國臨床藥理學雜誌
중국림상약이학잡지
THE CHINESE JOURNAL OF CLINICAL PHARMACOLOGY
2014年
7期
594-596,606
,共4页
李瑞芳%方伟进%曹珊珊%宋莹%李艳%王建刚%罗雪婷%孙哲臻
李瑞芳%方偉進%曹珊珊%宋瑩%李豔%王建剛%囉雪婷%孫哲臻
리서방%방위진%조산산%송형%리염%왕건강%라설정%손철진
肾性高血压%心肌纤维化%NAD( P) H氧化酶%结缔组织生长因子%阿托伐他汀
腎性高血壓%心肌纖維化%NAD( P) H氧化酶%結締組織生長因子%阿託伐他汀
신성고혈압%심기섬유화%NAD( P) H양화매%결체조직생장인자%아탁벌타정
renovascular hypertension%myocardial fibrosis%NAD ( P ) H oxidases%connective tissue growth factor%atorvastatin
目的:研究心肌纤维化时NAD( P) H氧化酶与转化生长因子( TGF)-β1、结缔组织生长因子( CTGF)的关系以及阿托伐他汀对心肌纤维化的作用。方法用两肾两夹法建立肾性高血压模型。给予阿托伐他汀10,5 mg· kg-1· d-1和坎地沙坦10 mg· kg-1· d-1,连续4周后,检测血流动力学参数、左心室/体重比率( LVW/BW);Masson染色检测心肌纤维化程度;Western-blot检测Nox4、TGF-β1和CTGF的表达。结果阿托伐他汀显著改善了高血压大鼠的心功能障碍和心肌纤维化程度,并且显著下调了Nox4、TGF-β1和CTGF在心肌组织的表达。结论阿托伐他汀能降低高血压大鼠心肌纤维化程度及改善心功能,其机制与抑制TGF-β1/Nox4/CTGF通路有关。
目的:研究心肌纖維化時NAD( P) H氧化酶與轉化生長因子( TGF)-β1、結締組織生長因子( CTGF)的關繫以及阿託伐他汀對心肌纖維化的作用。方法用兩腎兩夾法建立腎性高血壓模型。給予阿託伐他汀10,5 mg· kg-1· d-1和坎地沙坦10 mg· kg-1· d-1,連續4週後,檢測血流動力學參數、左心室/體重比率( LVW/BW);Masson染色檢測心肌纖維化程度;Western-blot檢測Nox4、TGF-β1和CTGF的錶達。結果阿託伐他汀顯著改善瞭高血壓大鼠的心功能障礙和心肌纖維化程度,併且顯著下調瞭Nox4、TGF-β1和CTGF在心肌組織的錶達。結論阿託伐他汀能降低高血壓大鼠心肌纖維化程度及改善心功能,其機製與抑製TGF-β1/Nox4/CTGF通路有關。
목적:연구심기섬유화시NAD( P) H양화매여전화생장인자( TGF)-β1、결체조직생장인자( CTGF)적관계이급아탁벌타정대심기섬유화적작용。방법용량신량협법건립신성고혈압모형。급여아탁벌타정10,5 mg· kg-1· d-1화감지사탄10 mg· kg-1· d-1,련속4주후,검측혈류동역학삼수、좌심실/체중비솔( LVW/BW);Masson염색검측심기섬유화정도;Western-blot검측Nox4、TGF-β1화CTGF적표체。결과아탁벌타정현저개선료고혈압대서적심공능장애화심기섬유화정도,병차현저하조료Nox4、TGF-β1화CTGF재심기조직적표체。결론아탁벌타정능강저고혈압대서심기섬유화정도급개선심공능,기궤제여억제TGF-β1/Nox4/CTGF통로유관。
Objective To investigate the effect of the atorvastatin in the myocardial fibrosis and study the relationship of Nox 4 and connective tis-sue growth factor ( CTGF ) .Methods The two -kidney two -clip (2K2C) method was used to induce renovascular hypertension.After ator-vastatin (10, 5 mg· kg-1 · d-1 ) and candesartan (10 mg· kg -1 · d-1 ) were given for 4 weeks, hemodynamic parameters were measured and left ventricular weight to body weight ( LVW/BW) ratio was calculated.Mor-phological analysis was performed by using Masson staining.Western -blot was used to investigate the expression of Nox 4 , transforming growth factor(TGF) -β1 and CTGF in left ventricle ( LV).Results Aortic systolic pressure ( AoSP) ,aortic diastolic pressure ( AoDP) ,left ventricu-lar end-systolic pressure (LVESP),left ventricular end-diastolic pres-sure ( LVEDP) and LVW/BW ratio were markedly elevated while maxi-mum ascending rate of left ventricular pressure (+dp/dtmax ) and maxi-mum declining rate of left ventricular ( -dp/dtmax ) were significantly decreased in 2K2C rats.Atorvastatin or candesartan could prevente the decrease in +dp/dtmax or -dp/dtmax, however, atorvastatin had no significant blood -lowing effects.LVW/BW ratio and left ventricular perivascular collagen fraction ( PCVF ) increased significantly in hyper-tension rats.Both atorvastatin and candesartan partly reversed these effects and improved the cardiac hypertrophy and fibrosis.The expressionof Nox4, TGF-β1 and CTGF increased significantly in LV of 2K2C rats while their levels were down -regulated with drugs given.Conclusion The Nox4 involves in myocardial fibrosis regulated by TGF -β1 and CTGF in renovascular hypertensive rats.Atorvastatin may attenuate myocardial fibrosis of 2K2C rats and improve their cardiac function , the inhibition of TGF-β1/Nox4/CTGF pathway possibly contributes to these effects.