Study On The Ziyin Qianyang Decoction On Spontaneously Hypertensive Rats Based On Rho/ROCK Path Way

Objective:Object to observe the effects and mechanism of Ziyin Qianyang Decoction on myocardial fibrosis in spontaneously hypertensive rats(SHRs)and observe the effect and mechanism of Ziyin Qianyang Decoction on the Rho/ROCK signaling pathway.Methods:Forty 12-weeks-old male SHRs were selected and divided into four groups which called high-dose of Ziyin Qianyang Decoction group,low-dose of Ziyin Qianyang Decoction group,enalapril Li group and model group;in each group there are 10 SHRs.And there were 10 Wistar male rats which were 12-weeks-old as normal group.The drug was administered for Ziyin Qianyang Decoction group,low-dose of Ziyin Qianyang Decoction group,enalapril group and model group for six weeks in a row.And 0.9% Na Cl was administered for normal group,too.The systolic blood pressure of each group of rats was measured and recorded every two weeks.After 6 weeks of administration,the rats were killed and the hearts were removed.Masson staining was used to observe the pathological changes of rat heart;Western blot was used to examine the protein expression level of connective tissue growth factor(CTGF),collagen I,(Co I-1),α-smooth muscle actin,(α-SMA),Rho A and ROCK1;RT-PCR was used to examine m RNA expression level of Co I-1,CTGF,α-SMA,Rho A and ROCK1.Results:(1)Changes of blood pressure in rats of each group: After 2,4,6weeks of drug intervention,compared to the model group,high-dose of Ziyin Qianyang Decoction group,low-does of Ziyin Qianyang Decoction group,and enalapril Li group,the blood pressure of rats was remarkably reduced,(P<0.05);(2)Masson staining presentation: Only a small amount of blue myocardial collagen fiber proliferation was observed in the normal group,compared with the normal group,a large number of blue myocardial collagen fibers were observed in the myocardial tissue of rats in the model group,myocardial fibrosis is obvious;compared to model group,blue myocardial collagen fibers in myocardial tissue of rats in high-dose group of Ziyin Qianyang Decoction and enalapril group were significantly reduced,however,a large amount of blue myocardial collagen fiber proliferation was still observed in the myocardial tissue of rats in the low-dose group of Ziyin Qianyang Decoction;(3)Expression of Co I-1 protein and Co I-1m RNA in myocardial tissue of rats:compared with the normal group,the expressions of Co I-1 protein and Co I-1m RNA in the model group were significantly increased(P < 0.05);compared with the model group,the expressions of Co I-1 protein and Co I-1m RNA in the high-dose groups of Ziyin Qianyang Decoction and enalapril group were significantly reduced,(P<0.05),however,the expression levels of Co I-1 protein and Co I-1m RNA in the low-dose group of Ziyin Qianyang Decoction were not significantly reduced(P>0.05);(4)Expression of CTGF protein and CTGF m RNA in myocardial tissue of rats:compared with the normal group,the expressions of CTGF protein and CTGFm RNA in the model group were significantly increased(P < 0.05);compared with the model group,the expressions of CTGF protein and CTGFm RNA in the high-dose groups of Ziyin Qianyang Decoction and enalapril group were significantly reduced,(P<0.05),however,the expression levels of CTGF protein and CTGFm RNA in the low-dose group of Ziyin Qianyang Decoction were not significantly reduced(P>0.05);(5)Expression of α-SMA protein and α-SMA m RNA in myocardial tissue of rats: compared with the normal group,the expressions of α-SMA protein and α-SMAm RNA in the model group were significantly increased(P<0.05);compared with the model group,the expressions of α-SMA protein and α-SMAm RNA in the high-dose groups of Ziyin Qianyang Decoction and enalapril group were significantly reduced,(P < 0.05),however,the expression levels of α-SMA protein and α-SMAm RNA in the low-dose group of Ziyin Qianyang Decoction were not significantly reduced(P>0.05);(6)Expression of related factors and m RNA in Rho/ROCK signaling pathway:compared with the normal group,the expressions of Rho A、ROCK1 protein and Rho A、ROCK1m RNA in the model group were significantly increased(P<0.05);compared with the model group,the expressions of Rho A 、 ROCK1 protein and Rho A 、ROCK1m RNA in the high-dose groups of Ziyin Qianyang Decoction and enalapril group were significantly reduced,(P<0.05),however,the expression levels of Rho A、ROCK1 protein and Rho A、ROCK1m RNA in the low-dose group of Ziyin Qianyang Decoction were not significantly reduced(P>0.05);Conclusions:(1)Ziyin Qianyang Decoction can continuously bring down the blood pressure of spontaneously hypertensive rats;(2)Ziyin Qianyang Decoction can reduce the expression of CTGF,Co I-1,andα-SMA and reduce the pathological damage of myocardial fibrosis;(3)Ziyin Qianyang Decoction may inhibit or reduce the activation of Rho/ROCK signaling pathway,and thus inhibit the occurrence and development of myocardial fibrosis.