Rho/Rho激酶信号通路抑制剂与高血压大鼠的心血管重构关系

Rho/Rho kinase signaling pathway to inhibiting the cardiovascular remodeling of hypertensive rats

目的:探究辛伐他汀抑制高血压大鼠的心血管重构与Ras homologue/Regulator of Cullins kinase(Rho/Rho激酶)信号通路之间的相关性。方法:将60只大鼠按数字表法随机分为模型组和阴性对照组,2组均正常饮食,模型疗组加用一氧化氮合酶抑制剂L-NAME溶于生理盐水按照剂量(6 mg.kg-1.d-1)每天灌胃给药1次,连续3周,建立高血压模型,后将模型组按数字表法随机分为治疗1组,治疗2组,治疗3组,每组9只大鼠,分别给予0.1,1,10 mg.kg-1辛伐他汀水溶液灌胃,每日1次。对照组不给予辛伐他汀,仅给予等量的生理盐水灌胃。观察不同剂量下主动脉组织结构变化,RT-PCR法检测Rho激酶mRNA表达变化并用Western-blot检测治疗前后Rho激酶蛋白表达变化。结果:模型顺利建立,造模后,与阴性对照组相比,模型组大鼠Rho激酶mRNA转录显著上调,(P<0.05),Rho激酶水平有显著性差异(P<0.05),主动脉内膜增生较对照组明显(P<0.05);随着辛伐他汀剂量增加,Rho激酶mRNA转录逐渐下调,(P<0.05);大鼠Rho激酶逐渐降低(P<0.05),主动脉重构程度逐渐降低(P<0.05)。结论:辛伐他汀能够通过Rho/Rho激酶信号通路抑制高血压大鼠的心血管重构。

OBJECTIVE To explore the correlation between the effect of simvastatin on cardiovascular remodeling of hyper- tensive rats and Ras homologue/Regulator o{ Cullins kinase（Rho / Rho kinase） signaling pathway. METHODS 60 male rats were randomly divided into control and model group, both groups were given with a normal diet, the model group using nitric oxide synthasc inhibitor L-NAME dissolved in saline in accordance with the close （6 rag. kg-1. d 1 ） each day garage for 3 con- secutive weeks, to establish a model of hypertension. Then the rats of model group were randomly divided into treatment group 1, treatment group 2 and the treatment group 3（n = 9）, the rats were given 0. 1, 1, 10 mg.kg i simvastatin aqueous solution gavage, once a day. The control group was not given simvastatin, only given the same amount of saline. The structural chan- ges of aortic tissue were observed after different doses of simvastatin treatment, and Rho kinase （Rho associated kinase） ehan ges detected by Western blot be{ore and after treatment. RESULTS After set up the model, the level of Rho-kinase in model rats increased significantly, compared to the control group with a significant difference （P〈0. 05）, Rbo kinase mRNA tran- scription significantly up-regulated （P〈0. 05）. Aortic intimal showed hyperplasia compared with the control group （P〈 0. 05）. After simvastatin treatment, the Rho-kinase mRNA transcription gradually down-regulated （P〈0. 05）; Rho kinase of the treated rats gradually lowered （P〈0. 05）, and the aorta remodeling gradually reduced （P〈0. 05）. CONCLUSION Simv- astatin inhibits the cardiovascular remodeling of hypertensive rats through the Rho / Rho kinase signaling pathway.