| Hypertension is a disease characterized by elevated arterial pressure,which has high incidence,many complications and is not easy to cure.According to previous reports,hypertension has become the most common chronic disease in the world.Hypertension is accompanied by a variety of complications,such as kidney damage,fatty liver and so on.In recent years,complications of hypertension have made it more difficult to control blood pressure.Shunaoxin pill is composed of chuanxiong and angelica.Previous studies have shown that shunaoxin pill has antihypertensive effect on spontaneously hypertensive rats,but the antihypertensive mechanism is still unclear.Captopril is an ace inhibitor widely used in the treatment of hypertension and cardiovascular disease.Therefore,this study intends to explore the antihypertensive mechanism of shunaoxin pill and its protective effect on kidney damage in spontaneously hypertensive rats based on network pharmacology and in vivo experiments.At the same time,to investigate the antihypertensive and renal protective effects of shunaoxin pill combined with captopril on spontaneously hypertensive rats.Firstly,network pharmacology was used to predict the antihypertension-related target pathways and biological processes involved in shunaoxin pill.Studies have shown that shunaoxin pill is involved in the regulation of blood circulation and blood pressure.Shunaoxin pill may act on NOS3 target,act on cGMP-PKG signaling pathway and regulate arginine and proline metabolism to achieve antihypertensive effect.The model of spontaneous hypertensive rat was used to verify the correlation of the target.Shunaoxin pill can effectively reduce blood pressure and keep blood pressure stable with long-term medication.Correlation biochemical analysis also proved that shunaoxin pill could effectively regulate NO/eNOS.At the same time,the content of ROS,reduced glutathione and the expression levels of Nrf2 and HO-1 proteins were detected to confirm that shunaoxin pill can reduce the kidney damage caused by hypertension by reducing oxidative stress.In addition,this study investigated the antihypertensive mechanism and renal protective effect of shunaoxin pill combined with captopril on spontaneously hypertensive rats.The decrease of blood pressure in combination group was better than that in captopril group.At the same time,the combination of drugs can effectively reduce the thickness of the aortic wall.Blood pressure was reduced by regulating NO/eNOS,ET-1,and dyslipidemia.At the same time,the combination therapy has a good protective effect on kidney tissue.Combination therapy reduced Cr and BUN levels more effectively than captopril alone.At the protein level,western blot was used to detect the expression of inflammatory cytokines and apoptosis-related proteins in renal tissues.Results showed that the combined treatment group significantly increased the levels of Bcl-2 and significantly reduced the protein expression of IL-1β,NF-κB,Bax,Cyt c,caspase 3,8 and 9 in renal tissue.The results showed that the performance of shunaoxin pill combined with captopril group on Cyt c,Bcl-2 and caspase 9 was better than that of captopril group.We speculate that the basis of combined therapy for renal protection is to reduce the release of inflammatory factors and inhibit the expression of apoptotic markers.In summary,this study demonstrated that shunaoxin pill play its antihypertensive and kidney-protective effects by acting on eNOS to regulate NO levels and improve oxidative stress levels.The combination of shunaoxin pill and captopril can reduce the release of inflammatory factors and inhibit the expression of apoptotic markers,and reduce the kidney damage in spontaneously hypertensive rats. |