| 1.ObjectiveBasic and clinical researches were conducted to investigate renal damage of hypertension in the early stage.To demonstrate whether QianYangYuYin granules(QYYYG),the characteristic preparation of the TCM hospital of Jiangsu provincecouldreduce the metabolic disorder of AA and inhibit inflammatory factorthrough investigating the effect of relative proteins in HUVEC cell injury model.To confirm whether QYYYG can improve the corresponding indicators of renal damage of hypertension in the early stage through clinical study,.And to search for the risk factors of renal damage of hypertension in the early stage.Further evidence can be provided for the TCM intervention of renal damage of hypertension in the early stage.2.Methods and Contents2.1 Basic research2.1.1 MethodsThe influence of QYYYG on the expression of active oxygen and relative protein in HUVEC cell injury model:SD rats were randomly divided into normal group,Valsartan capsules group,QYYYG group,QYYYG combined with Valsartan capsules group,with 8 rats in each group.The SD rats were fed by way of i.g.continuously for 7 days,including QYYYG 2 times/d with 10 g/kg/d and valsartan once daily with 0.027/kg/d.Then the serum containing drugs were prepared.HUVEC was divided into 5 groups.Except for the normal group,the other groups were treated with AngⅡ to establish the model of apoptosis injury in the exponential phase HUVEC.After modeling,the groups were given the corresponding prepared serum respectively:control group(10%blank serum medium),model group(10%blank serum medium),valsartan group(valsartan 10%serum medium),QYYYG group(10%QYYYG serum medium),QYYYG combined with valsartan(10%valsartan +10%QYYYG group serum medium),and were cultured for 24 h.2.1.2 Observation:1)the effect of serum containing drugs on the activity of the damaged HUVEC induced by AngⅡby MTT method;2)the effect of serum containing drugs on the shape of HUVEC induced by Angll injury by the fluorescence microscope;3)the effect of serum containing drugs on the accumulation of active oxygen in the injury cell model;4)the influence of the medicated serum on NF-κB p65 in the cellular HUVEC damage model;5)the influence on COX-1 and COX-2 in the cell model;6)the effect on PGES and PGIS in the cell model.2.1.3Results:The results of intervention by the serum containing different drugs showed that:1)Compared with the control group,the survival rate of HUVEC cells in model group decreased considerably(P<0.01).When given the serum to intervention,cell survival rate was significantly increased compared with the model group(P<0.01).There are more living cells in the group of valsartan combined with QYYYG than that in the valsartan group(P<0.01).2)Compared with the control group,the level of reactive oxygen species in model group was greatly increased(P<0.01).Given the medicated serum,the level of reactive oxygen in every group decreased significantly(P<0.01).The decrease of level of reactive oxygen in the cell model of HUVEC injury in valsartan and QYYYG group was more noticeable(P<0.05).3)The expression of NF-κB p65 in the cell model group was significantly increased(P<0.01);compared with the model group,the expression of NF-κB p65 in each group was significantly decreased(P<0.01).The expression of NF-κB p65 reduced more obviously in valsartan combined with QYYYG group than valsartan group(P<0.05).4)Compared with the control group,the expression of COX-2 protein in cell model group were significantly increased(P<0.01).The expression of COX-2 in each treatment group level was obviously lower than the model group(P<0.01).While the expression of COX-1 had no significant difference.5).Compared with the model group,the expression level of PGES and PGIS in each group decreased drastically(P<0.01).The drug combination group decreased more apparently.There was a significant difference between PGIS in the serum administration group of valsartan combined with QYYYG group and that of the valsartan group(P<0.01).2.1.4Conclusion:1).QYYYG can significantly improve the survival rate of HUVEC damage induced by AngⅡ;and reduce activeoxygen.2).QYYYG can significantly improve the inflammatory reaction of HUVEC damage nduced by AngⅡ,the possible mechanism is associated with the decrease of inflammatory mediators of NF-κB p65 and COX2.3).The mechanism of the antagonism of the apoptosis of HUVEC induced by AngⅡ may be related to the down-regulation of the expression of PGES and PGIS.4).The protective effect of QYYYG&Valsartan Capsules on HUVEC damage was better than that of Valsartan Capsules alone.2.2 Clinical study2.2.1 MethodsClinical study of QYYYG intervention of early renal damage in hypertension:Choose patients aged 35-75,who suffered from primary 2 or 3 grade hypertension,with the liver fire hyperactivity or yin deficiency and yang hyperactivity,eGFR>60mL·min-1·1.73m2-1,ACR nomal,The volunteers,having agreed for testing and signed informed consent forms,were divided into experimental group and control group randomly at the ratio of 1:1.The experimental group used QYYYG and standard western medicine antihypertensive therapy(with ACEI or ARB based therapy,can be combined with CCB),and the control group used western medicine treatment only.The observation period was 6 months,and the observation index are as follows:the mALB,urinary ACR,eGFR,NGAL,KIM-1,IL-18,demographic data,vital signs and biochemical indicators of two groups before and after treatment using SPSS 20.0 for two independent samples t test between the two groups.2.2.2.Results:1).The demographic characteristics,vital signs,biochemical index,urinary albumin,urine ACR,eGFR and other data were not statistically different between the experimental group and the control group,which indicates that two groups are comparable to the baseline.2).After 6 months of observation,there was no statistical difference between the control groupand test group among the demographic characteristics,vital signs,biochemical index,urinary micro-albumin,urine ACR and eGFR.The serum NGAL,which is the index decreased early renal damage,showed statistical difference(P<0.05)with the x ± SD as(9.578±25.871)mg/L,when compared intra test groups.While the x±SD of control groups was(9.318±65.629)mg/L intra the groups,had no significant differences.In the improvement of NGAL,the results of t test between groups showed that the value of test groups was(155.961±62.884)ng/mL and that of control groups was(172.625±88.373)ng/mL before concluded in the groups.After given the drugs for 6 months,the value of test groups decreased to(131.611±46.576)ng/mL,that of control groups was(158.180±61.502)ng/mL.The P value was 0.024 and had statistical difference between the groups after the 6-month treatment.The result of compared t test showed that x±SD was(22.5347±56.391)ng/mL and P value was 0.011 in test groups,with significant difference.But the control groups was(18.1929±79.215)ng/mL with no significant difference.Also,there were no significant differences in the experimental group in the IL-18、KIM-1 intra and between the groups(P>0.05).2.2.3 Conclusion:After 6 months of intervention,QYYYG can improve the expression of NGAL in early renal damage of hypertension patients,and decrease the trend of micro-albuminuria.2.3 Epidemiological investigation2.3.1 MethodsInvestigation on the risk factors of renal damage of hypertension in Nanjing community:Accepted the complete medical data of the outpatients diagnosed as hypertensive patients and healthy people,from the Daguang community in Qinhuai District Community Health Center system,from January 2015 to December 2016.Using the single factor group T test,according to the eGFR<90 and>90 mL/min/1.73m2,the patients were divided into two groups to analyze Height,Weight,HR analysis,SBP,DBP,ALT,AST,TBIL,BUN,TC,HDL-C,LDL-C,TG,WBC,RBC,blood PLT,Hb，and the difference between the patients with coronary heart disease and diabetes,and take on the correlation analysis,using eGFR as the dependent variable and above mentioned factors as independent variables.2.3.2 Results:1).The physical examination data of 3413 subjects were obtained.Among them,2697 cases were eligible for the plan,including the healthy population of 1309 cases,and the hypertension patients of 1388 cases.Among the hypertension subjects,660 cases were simple hypertension,297 cases were hypertension combined with diabetes,and 124 cases were combined with coronary heart disease.2).In healthy people or hypertension patients,using the group t test method to analyze the level of eGFR.It showed that there were significant statistical differences between men and women(P<0.001),and females’ eGFR value were higher than that of males.The eGFR was significantly negative correlated with BUN and UA(P<0.001),and there was significantly negative correlation with SBP and DBP(P<0.01),and negatively correlated with TBIL(P<0.05).In 1388 cases of hypertension patients,the results showed that there was a significant negative correlation between eGFR and TG(P<0.001),and eGFR was more significantly decreased in patients with coronary heart disease(P<0.001).Analysis of 660 cases of simple hypertension group showed a negative correlation between eGFR and body weight(P<0.05).There was a significant negative correlation between hypertension and eGFR in healthy subjects(P<0.001).3).Linear multiple regression analysis revealed that eGFR was negatively correlated with LDL-c,FBG and WBC(P<0.05),and had a significant negative correlation in the BUN,UA and SBP(P<0.001),while eGFR was positively correlated with RBC and PLT(P<0.05).2.3.3 Conclusion:In the Community population,the negative influence of eGFR may be related with age,body weight,TG,LDL-C,SBP,PP,BUN,UA and FBG.eGFR values in men were lower than that in women.Lower eGFR value was found in hypertensive patients than in healthy subjects and more lower in hypertension patients with cormorbidity of coronary artery disease. |
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