丹参酮ⅱa对肾性高血压大鼠心肌胶原代谢影响的机制研究

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1、安徽医药AnhuiMedicalandPharmaceuticalJournal2011Sep；15(9)·1065·丹参酮HA对肾性高血压大鼠心肌胶原代谢影响的机制研究方健，王浩奎(广东省广州市花都区人民医院药剂科，广东广州510800)摘要：目的研究丹参酮HA(TanshinoneHA，Tsn)对两肾两夹(two—kidneytwo—clip，2K2C)。肾性高血压大鼠心肌I型胶原基因表达、蛋白含量的影响。方法制作两肾两夹肾性高血压大鼠模型，Tsn70mg-kg～·d(高剂量)和35mg·kg～·d(低剂量)、缬沙坦(Va

2、lsartan)26．7mg·kg～·d连续灌胃给药6周，WesternBlot检测心肌组织I型胶原(collagentypeI，CollagenI)蛋白表达；RT—PCR检测心肌组织CollagenI水平。结果Tsn高剂量组、低剂量组和缬沙坦组CollagenI蛋白含量明显低于两。肾两夹模型组，分别下降了59．3％、24．6％和63．2％，Tsn高剂量组、低剂量组、缬沙坦组和两肾两夹模型组之间的CollagenImRNA水平无明显差别，这提示1rsn和缬沙坦对CollagenImRNA水平无下调作用，二者并不是通过Colla

3、genI基因转录调控以改变胶原含量，而是与转录后和／或翻译后调控有关。结论Tsn对两肾两夹高血压大鼠左室心肌CollagenImRNA水平无下调作用，但抑制心肌CollagenI蛋白表达，提示Tsn并不是通过CollagenI基因转录调控以改变胶原含量，而是与转录后和／或翻译后调控有关。关键词：丹参酮ⅡA；两肾两夹肾性高血压大鼠；I型胶原蛋白Long-timeefectsofTanshinoneHAonCollagenIexpressioninratswithrenovascularhypertensi0nFANGJian．W

4、ANGHao．kui(HuaduPeople'sHospital，Guangzhou，Guangdong510800，China)Abstract：AimToevaluatetheeffectsofTsntheproteinlevelofCollagenIandthemRNAlevelsofCollagenIinratswithrenovascularhypertension．Methods2K2CoperationwasmadetoSDratstoestablishhypertensionandLVfibrosismode1

5、．Fivegroupsofratswereestablishedfromthe4thweekafter2K2C：(1)sham—operatedgrouptreatedfor6weekswithplacebo(0．5％carboxymethylcelluloseso—dium，solventforTsnandValstarn)；(2)agroupwith2K2Chypertensiontreatedfor6weekswithplacebo(0．5％carboxymethylcellu-losesodium)；(3)agroup

6、with2K2Chypertensiontreatedfor6weekswithTsn(70mg·。。·d)；(4)agroupwith2K2Chyper-tensiontreatedfor6weekswithTsn(35mg·kg。。·d‘。)；(5)agroupwith2K2Chypertensiontreatedfor6weekswithValsartan(26．7mg·kg～·d)．Placebo，TsnandValsartanweregivenbygavage．WemeasuredtheproteinofCollag

7、enIbyWesternblota·nalysis，mRNAlevelsofCollagenI，MMP-2，MMP-9，TIMP一1andTIMP-2byRT—PCR．ResultsIncontrasttosham-operatedgroup，themRNAandproteinlevelsofCollagenIin2K2Cuntreatedgroupweresignificantlyincreased．Tsn70mg·kg～，35mg·kg～andVal-sartan26．7mg·kg～didnotsuppresstheinc

8、reaseinmRNAlevels，however，theysignificantlydecreasedtheproteinlevels．ConclusionTsndecreasedtheCollagenIcontentonthelevelofposttranstricpti