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

Long-time effects of TanshinoneⅡA on Collagen I expression in rats with renovascular hypertension

目的研究丹参酮ⅡA(TanshinoneⅡA,Tsn)对两肾两夹(two-kidney two-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,Tsn 70 mg·kg-1·d-1(高剂量)和35 mg·kg-1·d-1(低剂量)、缬沙坦(Valsartan)26.7 mg·kg-1·d-1连续灌胃给药6周,Western Blot检测心肌组织I型胶原(collagen type I,Collagen I)蛋白表达;RT-PCR检测心肌组织Collagen I水平。结果 Tsn高剂量组、低剂量组和缬沙坦组Collagen I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Collagen ImRNA水平无明显差别,这提示Tsn和缬沙坦对Collagen I mRNA水平无下调作用,二者并不是通过Collagen I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Collagen I mRNA水平无下调作用,但抑制心肌Collagen I蛋白表达,提示Tsn并不是通过Collagen I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。

Aim To evaluate the effects of Tsn the protein level of Collagen I and the mRNA levels of Collagen I in rats with renovascular hypertension.Methods 2K2C operation was made to SD rats to establish hypertension and LV fibrosis model.Five groups of rats were established from the 4th week after 2K2C：（1） sham-operated group treated for 6 weeks with placebo（0.5% carboxymethyl cellulose sodium,solvent for Tsn and Valstarn）;（2） a group with 2K2C hypertension treated for 6 weeks with placebo（0.5% carboxymethyl cellulose sodium）;（3） a group with 2K2C hypertension treated for 6 weeks with Tsn（70 mg·kg-1·d-1）;（4） a group with 2K2C hypertension treated for 6 weeks with Tsn（35 mg·kg-1·d-1）;（5） a group with 2K2C hypertension treated for 6 weeks with Valsartan（26.7 mg·kg-1·d-1）.Placebo,Tsn and Valsartan were given by gavage.We measured the protein of Collagen I by Western blot analysis,mRNA levels of Collagen I,MMP-2,MMP-9,TIMP-1 and TIMP-2 by RT-PCR.Results In contrast to sham-operated group,the mRNA and protein levels of Collagen I in 2K2C untreated group were significantly increased.Tsn 70 mg·kg-1,35 mg·kg-1 and Valsartan 26.7 mg·kg-1 did not suppress the increase in mRNA levels,however,they significantly decreased the protein levels.Conclusion Tsn decreased the Collagen I content on the level of post transtricption or translation.