Study On The Protective Mechanism Of "Tiandan Jiangya Granule" On Vascular Endothelial Inflammatory Injury Mediated By TLR4 Pathway In SHR Hyperactivity Of Liver-yang Model

Objective:Shenfu injection was injected intravenously to establish the model of hyperactivity of liver and Yang in SHR rats.The effects of different drugs on hyperactivity of liver and Yang were investigated.This study in spontaneously hypertensive rats(SHR)of liver Yang sy ndrone model as the research object,by looking at the different dose day Dan step-down particles,candesartan ester after intervention in bl ood pressure,plasma Renin,Ang?,ALD TLR4 content,abdominal aort a endothelial cells,the nf-kappa Bp65,TNF alpha,the change of IL6 expression level,explore the day Dan step-down granules on blood pressure of SHR liver Yang syndrone model intervention mechanism i s associated with the vascular endothelial inflammatory injury of TLR 4 pathway mediated,and provide the experimental basis for its clinica 1 application..Methods:Fifty male SHRs without specific pathogens(SPF)were inj ected with Shenmai injection 8ml/kg intravenously for 4 weeks to repl icate the hyperactivity model of liver and Yang in SHR rats.Building successful after rats were randomly divided into 5 groups,each grou p of 10,SHR respectively made module(8 ml distilled water(kg·d)-1 continuous lavage 8 weeks),day Dan step-down particles low,m edium and high dose group(1 g/ml,respectively,2 g/ml,concentratio n of 4 g/ml,with 8 mg(kg·d)-1,continuous lavage 8 weeks),ca ndesartan ester mixed suspension group(0.8 mg(kg·d)-1,continu ous lavage 8 weeks);In addition,10 SPF class male homologous nor mal blood pressure rats(Wistar-kyoto,WKY)at the same week of age were used as control group(8ml(kg·d)-1 of distilled water for 12 c onsecutive weeks),and 10 SPF class male SHR rats were used as con trol group(8ml(kg·d)-1 of distilled water for 12 consecutive week s).During the administration,the changes of spirit,body weight,resp iratory rate and food intake of each group were observed every day.Four weeks after modeling,the success of modeling was evaluated by observing the systolic blood pressure of the caudal artery,24h water intake,irritability degree and pain threshold sensory temperature of t he modeled rats.After successful modeling,the systolic and diastolic blood pressures of rats in each group were measured 12,24,36,48 a nd 60 days after administration.Results:1.Identification of SHR liver Yang hyperactivity model:The systolic blood pressure,24 h water intake,irritability degree and the number of conjunctival hyperemia animals in SHR model group were significantly higher than those in normal control group and SHR control group(P<0.01).2.1 Systolic blood pressure:the Tiandan Jiangyan Granules intervention group and the Candesartan Dixide intervention group was significantly increased at each detection time point(P<0.05).Compared with SHR build module,day Dan step-down granule low-dose group when dosing 36 days to detect systolic blood pressure decreased(P<0.05),the day Dan step-down particles dose groups in dosage on the 24th day detect systolic blood pressure decreased(P<0.05),the day Dan step-down particles high-dose group,candesartan ester group when dosing 12 days to detect systolic blood pressure decreased(P<0.05).2.2 Tiandan Jiangya granules intervention group and Candesartan diastolic blood pressure intervention group were significantly increased at each detection time point(P<0.05).Compared with SHR build module,day Dan step-down granule low-dose group in dosing 60th day detecting diastolic blood pressure decreased(P<0.05),the day Dan step-down particles dose when dosing 36 days testing,diastolic blood pressure decreased(P<0.05),the day Dan step-down particles in high dose group dosing day 24 when diastolic blood pressure decreased(P<0.05),candesartan ester group in dosing day 12 detection decrease in diastolic blood pressure(P<0.05).3.Enme-linked immunoassay:the contents of plasma Renin,Ang? and ALD were determined.Compared with the normal control group and the SHR control group,the levels of serum Renin,Ang? and ALD were increased in the SHR model group,with statistical significance(P<0.01).Compared with the SHR model group,the levels of Renin,Ang? and ALD were decreased in the Tiandan Jiangyad Granules intervention group and the candesartan ester intervention group,with statistical significance(P<0.01).4.Western blot:TLR4,NF-?B expression:Compared with normal control group and SHR control group,serum TLR4,NF-?B levels in SHR model group were increased,with statistical significance(P<0.01);Compared with the SHR model group,the levels of TLR4,and NF-?B were decreased in the Tiandan Jiangya Granules intervention group and candesartan ester intervention group,with statistical significance(P<0.01).5.ELISA detection of IL-6 and TNF-a expression:Compared with the normal control group and the SHR control group,serum IL-6 and TNF-a levels in the SHR model group were increased,with statistical significance(P<0.01);Compared with the SHR model group,the levels of IL-6 and TNF-a in each dose of Tiandan Jiangya Granules intervention group and candesartan ester intervention group were decreased,with statistical significance(P<0.01).Conclusion:1.It is feasible to establish the model of hyperactivity of liver Yang by intravenous injection of Shenfu injection,with high success rate and low mortality rate.2.Day Dan step-down particles have good antihypertensive effect,and has good safety and efficacy,can reduce the Ang 1 in the plasma of rats,Ang ?,ALD content,TLR4 abdominal aorta endothelial cells,the nf-kappa Bp65,TNF alpha,IL-6,the TLR4 pathways through lowering blood pressure,inhibit inflammation factor expression and reduce the role of vascular endothelial injury is clear.