Research On The Relationship Between The Expression Of Serum "Ghrelin-Growth Hormone Signaling System" And TCM Syndromes In Patients With Salt Sensitive Hypertension

Salt sensitive hypertension is a special type of essential hypertension,as the cause of high blood pressure,blood pressure raised up after high salt die,and showed the body’s tolerance to salt and sodium metabolic disorders.At the same time,there is a serious damage to the tissues and organs,the study suggests that the damage often exists before the blood pressure rises.Therefore,salt sensitive hypertension is a kind of clear and specific pathogenesis of hypertension.Salt sensitive hypertension patients usually have prominent characteristics of syndrome in traditional Chinese Medicine,there are some similarities and differences in the syndrome evolution and prognosis.Based on the study of the clinical rule of salt sensitive hypertension,on the one hand,the study of the pathogenesis of salt sensitive hypertension was carried out.On the other hand,the TCM syndrome research about clinical symptoms was taked,summed up the most prominent,the most common and can reflect the characteristics of pathogenesis,and then the main syndromes of the clinical rules and possible material foundation for in-depth study.1.Purpose:1.1 According to the clinical characteristics of salt sensitive hypertension are summarized,bioinformatics research in hormone signaling system of salt sensitive hypertension Ghrelin-growth,trying to find the possible pathogenesis of salt sensitive hypertension.1.2 By analyzing the TCM syndrome characteristics and distribution of salt sensitive hypertension,summed up the syndromes of representative types of salt sensitive hypertension,according to the Bioinformatics study of Ghrelin-growth hormone signaling system and Clinical characteristics analysis explore the objective material basis of salt sensitive hypertension syndromes of TCM.2.Method:2.1 Study on the clinical characteristics of hypertension:The ambulatory blood pressure monitoring were used to evaluate blood pressure in salt sensitive hypertensive;Dynamic ECG heart rate variability to evaluate the autonomic nervous tension of the salt sensitive hypertensive;Glomerular filtration rate and urinary albumin to evaluate renal damage;Serum renin,angiotensin II,angiotensin I,aldosterone to evaluate the renin angiotensin system;Insulin sensitivity index to evaluated the insulin resistance;Color Doppler ultrasound to evaluate cardiac function and carotid atherosclerosis;Observed the blood biochemical,blood routineand the thyroid function index.2.2 Study on TCM syndrome of salt sensitive hypertension:Using epidemiological methods to collect the clinical symptoms and signs.Collated the syndrome scale and analyzed the collated information.First of all,through the factor analysis to reduce the dimension of the information,to reduce the number of factors that can fully explain the overall difference,and the common factor of TCM syndrome elements,the disease of the viscera.Then the clustering of common factors was used to reduce the dimensions of the similar syndrome elements,and the main clinical syndrome types were induced by the combination of TCM theory.Finally,the clinical information of each group of salt sensitive hypertension was studied.2.3 Experimental study on Ghrelin-growth hormone signaling system:Selected 36 cases of salt sensitive hypertension(including 3 TCM syndrome group with 12 cases in each group,30 cases)and non salt sensitive hypertension 16 cases of normal medical personnel randomly,the use of Ghrelin/Obestatin Obestatin serum Ghrelin ELISA kit to detect 15 cases of hypertension were randomly selected;sensitivity(including the spleen and kidney yang,water retention group of 6 cases,5 cases of phlegm dampness group,yin deficiency and yang hyperactivity group 4 cases),15 cases of non salt sensitive hypertension 6 cases of normal medical personnel.Quantitative analysis of 40 protein factors of growth factor signaling system using QAH-GF-1 protein chip.2.4 Statistical methods:data using SPSS 13 statistical software for data analysis,count data using chi square test;standard deviation measurement data(X + SD);P≤0.05 for statistical difference.When comparing the measurement data between groups,the variance homogeneity was analyzed by single factor analysis of variance,and Kruskal rank sum test was used if the variance was not uniform.The Microsoft excel2014 software was used to draw the chart.Factor analysis and cluster analysis of R system were used in the study of syndromes.3.Results:3.1 Salt sensitivity hypertension clinical characteristics research resultsIn hypertension patients a total of 279 cases,including improved fast salt load test positive for 131 cases of hypertension patients identified as salt sensitivity,47%of the proportion of high blood pressure.Both no differences in age and gender ratio.3.1.1 Course of the comparison results between groups:salt sensitivity hypertension illness duration longer than the patients with high blood pressure,salt sensitivity obviously significant difference.3.1.2 Group size between the results of the study:salt sensitivity high blood pressure,BMI,6,neck circumference were significantly higher than those of high blood pressure,salt sensitivity and normal group;Hip circumference is significantly higher than normal group.The salt sensitivity high blood pressure,BMI,and neck circumference is significantly higher than normal group.3.1.3 Blood pressure comparison results between groups:24NASBP,24HADBP,NADBP,DASBP,NASBP,24 hAPP,24 HSBPV,NAPP,DSBPV,NSBPV,24 HDBPV,NDBPV,24 SBPL,24 DBPL,DSBPL,NSBPL,NDBPL:hypertension group>salt sensitivity of salt sensitivity hypertension group,significant difference;Hypertension group<NSBPRR,NDBPRR salt sensitivity than salt sensitivity hypertension group,significant difference;3.1.4 Group between heart rate variability research results:24 h total salt sensitivity high blood pressure,average heart rate,heart rate were significantly higher than the salt sensitivity hypertension group;Salt sensitivity SDNN hypertension group,SDANN,SDSD,triangle index,RMSSD,Pnn50 hypertension group were significantly lower than the salt sensitivity3.1.5 Kidney function results between groups:salt sensitivity GFR hypertension patients significantly lower than the salt sensitivity high blood pressure and the normal group,rather than salt sensitivity without hypertension patients and normal differences.Urinary microalbumin,alpha microglobulin,urinary albumin creatinine ratio:salt sensitivity hypertension group>the salt sensitivity hypertension group>normal group;Urine immunoglobulin salt sensitive group is significantly higher than the other two groups,the significant difference;Urine NAG enzyme,no difference between groups.3.1.6 Insulin sensitive index results between groups:salt sensitivity high blood pressure,high blood pressure,insulin sensitivity index was significantly lower than the salt sensitivity and normal group,rather than high blood pressure,salt sensitivity and normal group,no difference.3.1.7 Renin angiotensin results between groups:angiotensin Ⅱ(AngⅡ)salt sensitivity hypertension group>the salt sensitivity hypertension group>normal group,and two more significant difference;Aldosterone(ALD)is sensitive to salt high blood group was significantly higher than salt sensitive and normal group,the difference is significant.Renin activity(PRA)normal group significantly lower than the other two groups,the significant difference.AngⅠ no significant difference between groups.3.1.8 Group of blood lipid metabolism between the results of the study:CHO:high blood pressure,salt sensitivity and the salt sensitive total cholesterol levels significantly higher than the normal group,no significant difference between the two;TG:high blood pressure,salt sensitivity>the hypertension group>normal salt sensitivity,significant difference;HDL-C:salt sensitivity significantly below the salt sensitivity hypertension and normal group;LDL-C:high blood pressure,salt sensitivity and salt sensitivity high blood pressure is significantly higher than normal group,but no significant difference between the two;ApoAl:salt sensitivity hypertension significantly lower than normal group,and high blood pressure and salt sensitivity no difference;ApoB:no difference between groups;ApoB/ApoAl:hypertension is significantly higher than normal group,salt sensitivity difference is obvious.3.1.9 Group between main ion research results:the serum blood blood k,Mg normal group was obviously higher than that of high blood pressure,high blood pressure and the salt sensitivity,salt sensitivity Serum sodium salt sensitive group was obviously higher than that of non-sensitive hypertension and normal group.3.1,10 Between groups of serum cortisol and homocysteine results:COR between group level:high blood pressure,salt sensitivity>the hypertension group>normal salt sensitivity;Hypertension group between HCY:salt sensitivity>the hypertension group>normal salt sensitivity,are significant difference3.1.11 Biochemical and blood tests results between groups:blood BUN:high blood pressure,salt sensitivity>not salt sensitive,normal group;Blood UA:high blood pressure,salt sensitivity>the salt sensitive>normal group;The plasma total protein,albumin,globulin:normal group>high blood pressure,salt sensitivity,salt sensitivity difference is significant.Salt sensitivity hypertension HB,HCT,the MCV is below the salt sensitivity high blood pressure and the normal group,significant difference.3.1.12 Echocardiographic findings between groups:salt sensitivity hypertension interventricular septum,left ventricular posterior wall thickness is greater than the salt sensitivity high blood pressure and the normal group,significant difference;High blood pressure,salt sensitivity EF,FS%%higher than that of high blood pressure,salt sensitivity and normal group,significant difference;E/A:normal group>the salt sensitivity>salt sensitivity of hypertension.3.1.13 Group between carotid atherosclerosis research results:the carotid intima thickness salt sensitivity hypertension group was obviously higher than that of normal group.Positive rate of salt sensitivity high blood pressure and carotid plaques group is significantly higher than the salt sensitive group and normal group.3.2 Salt sensitivity hypertension TCM syndrome researchAccording to the 131 Chinese medicine clinical symptom score information,symptoms after finishing,remove low frequency symptoms,analysis of 59 main symptoms.Factor analysis of the total dimension reduction five common factor and level according to the factor score to classify patients with high blood pressure,salt sensitivity and statistic,a common factor includes the number of cases and percentage,factor 1(18.32%),factor of 2(21.37%),3(20.43%),a factor of 4(20.61%),factor 5(22.14%).Disease is an internal structure of than:spleen and kidney 21.37%and 17.56%,18.32%,18.32%of liver and spleen,spleen and kidney.Syndrome factor:Yin deficiency,phlegm wet 18.32%18.32%,and 21.37%42.75%,water to drink,deficiency,Yang deficiency,20.61%to 60.31%,loss of 17.56%,17.56%17.56%,hot gas,reversed flow of qi by 21.37%.Syndrome differentiation type:Yin hand,phlegmy wet indicates 18.32%and 21.37%,spleen kidney Yang deficiency,Yang deficiency water 20.43%and 20.61%.Then probability factor clustering analysis:factor 3/4/5 clustering into a category,the cluster into 3 categories:spleen kidney Yang deficiency,water to drink in stop card(60.31%),Yin hand syndrome(18.32%),Phlegmy wet indicates syndrome(21.37%).Then the three syndrome clinical physical and chemical indicators to compare between groups,the results show that the three syndromes between groups in the level of blood pressure,sympathetic nervous tension,renin angiotensin activity,the degree of insulin resistance and the degree of kidney damage,heart function damage degree,the degree of carotid atherosclerosis were significant differences.3.3 Ghrelin-growth hormone signaling system experimental study3.3.1 Ghrelin,Obestatin research results:the serum Ghrelin level salt sensitivity hypertension group was obviously lower than normal,and significantly lower than the salt sensitivity of hypertension patients.Instead of salt sensitivity hypertensive patients compared with normal person would not have obvious difference.No difference between Obestatin group.3.3.2 Between the three groups by analysis of variance of growth factor of salt sensitive hypertension increase for IGFBP-3,EG-VEGF,GDNF,IGFBP-2,GH,NT-4,PDGF-AA,PIGF,SCF R,VEGF R2,VEGF R3,VEGF-D MCSF,R increased,growth factor is lower,AR,HGF.3.3.3 Differences in protein bioinformatics research results:the Gene Ontology(Gene Ontology,GO)analysis of the structure analysis function of biological information database and KEGG biological information database was studied by means of biological information pathways(PATH WAY),according to the results of high blood pressure,salt sensitivity by growth factors involved in the pathogenesis of many possible pathways.Respectively is:tyrosine phosphorylation signalling network(inhibits PTP peptidyl-tyrosine phosphorylation),growth factor signaling pathway(growth factor activity),silk crack the original activated protein kinase(Mitogen activated protein kinase,MAPK),phosphate ester acyl inositol 3 kinase/silk/threonine kinase(PI3K/Akt phosphoinositide 3-kinase rine threonine kinase);The Ras signaling pathways(Ras signaling pathway);Rap1 signaling pathways(Rap 1 signaling pathway)3.3.4 Ghrelin,Obestatin,and between different TCM syndrome group protein chip research results:the spleen and kidney Yang deficiency,water to drink in serum Ghrelin stop group was obviously lower phlegmy wet indicates sheng group;Serum Obestatin phlegmy wet indicates sheng group was obviously higher than that of other two syndrome groups;Spleen and kidney Yang deficiency,water to drink to group compared with phlegm wet indicates sheng group raised has five,respectively is GH,NT,IGF-1-4,VEGF-D,bFGF,cut three,respectively is AR,Ghrelin,Obestatin;Spleen and kidney Yang deficiency,water to drink in stop group and Yin deficiency hand raised three,respectively is GH,NT,IGF-1-4,cut three,respectively is AR,HB EGF,Ghrelin;Phlegmy wet indicates sheng group compared with Yin deficiency group hand raised two Obestatin,VEGF R2,cut two,respectively is HB EGF,bFGF.3.3.5 The bioinformatics analysis of spleen and kidney Yang deficiency,water to drink to treat syndrome group compared with Yin deficiency hand syndrome differences in protein is mainly manifested in the biological process of growth hormone receptor signaling pathways(growth hormone receptor signaling pathway).Spleen and kidney Yang deficiency,water to drink to syndrome group compared with phlegm wet indicates sheng syndrome group differences in protein is mainly manifested in the epithelial cell proliferation in the process of biological pathways epithelial cell effort and enrichment of PI3K KEGG-Akt Phlegmy wet indicates sheng syndrome with Yin deficiency hand to compare differences in protein phosphorylation is mainly manifested in the biological process of lipid growth factor activity.4.Conclusion4.1 The common TCM Syndromes of salt sensitive hypertension are:deficiency of Spleen Yang and kidney yang,retention of water and retention of water;syndrome of yin deficiency and yang hyperactivity;phlegm dampness syndrome.4.2 Protein expression profile of salt sensitive hypertension Ghrelin-growth hormone signaling system:IGFBP-3,EG-VEGF,GDNF,IGFBP-2,GH,NT-4,PDGF-AA,PIGF,SCF R,VEGF R2,VEGF R3,VEGF-D MCSF,AR,HGF,upregulation of R,downregulation of Ghrelin.4.3 Salt sensitive hypertension is closely related to PTP,MAPK and PI3K-Akt signaling pathway.4.4 Protein expression profile in salt sensitive hypertension TCM syndrome"Ghrelin-growth hormone signaling system:spleen kidney yang deficiency,water retention syndrome,IGF-1,GH expression of NT-4,VEGF-D,AR,Ghrelin,upregulation of bFGF,Obestatin and.HB-EGF decreased;phlegm dampness,VEGF R2,Obestatin expression,AR HB-EGF,bFGF,upregulation of Ghrelin,GH,IGF-1,NT-4,VEGF-D decreased;Yin deficiency and yang hyperactivity expression of AR,HB-EGF,Ghrelin,HB-EGF,GH,IGF-1,upregulation of bFGF,NT-4,Obestatin,VEGF by R2.4.5 Salt sensitive hypertension,spleen kidney yang deficiency,water retention and retention of hormone and Growth signaling pathway receptor,Epithelial cell,PI3K-Akt signal pathway.Phlegm dampness syndrome is mainly related to lipid phosphorylation factor activity signal pathway of growth.Yin deficiency and yang hyperactivity syndrome were mainly related to Growth receptor signaling pathway,Growth factor signaling pathway signaling pathway.