Retrospective Study On The Distribution Of TCM Syndromes In Vascular Aging Patients With Hypertension And Mechanistic Research Of Ang Ⅱ/NLRP3 Inflammasome Mediating The Hypertensive Rats With Vascular Aging

Vascular aging(VA)is a major risk factor and driver of age related cardiovascular and cerebrovascular diseases,providing an environment for the development of cardiovascular and cerebrovascular diseases such as hypertension(HTN),atherosclerosis and stroke.Both VA and HTN are associated with changes in vascular tree morphology and function,characterized by increased atherosclerosis and vascular tone,decreased elasticity,impaired dilation,and so on.VA and blood pressure have a mutual relationship.On the one hand,elevated blood pressure is the clinical manifestation of VA,on the other hand,long-term HTN will lead to arterial wall damage,thus promoting stiffness and accelerating the aging of blood vessels.In this study,through the retrospective analysis of relevant data of clinical patients with VA accompanied with HTN,and the discussion of VA related signal pathways in hypertensive rats,so as to explore the distribution characteristics of TCM syndromes in patients with VA accompanied with HTN and the possible mechanism of the effect of HTN on VA,so as to provide reference for the study of TCM intervention and mechanism of VA.There are three parts,literature review,clinical and basic research.1.Literature reviewBy sorting out and summarizing the correlation between VA and HTN and the related literature on signal pathways,the possible mechanism of the effect of HTN on VA was understood.By reviewing and summarizing the literature related to the understanding of TCM on VA,this paper preliminarily understands the understanding of TCM on the etiology and pathogenesis of VA,as well as the current prevention and treatment status of TCM on VA.2.Clinical researchRetrospective study on the distribution of TCM syndromes in vascular aging patients with hypertensionObjective:By analysing the relevant case data of patients with VA accompanied with HTN retrospectively,the distribution characteristics of TCM syndromes in patients with VA accompanied with HTN and the possible influence of HTN on VA will be explored.Methods:A total of 60 VA patients with HTN admitted to the geriatrics department or general medicine department of Xiyuan Hospital,China Academy of Chinese Medical Sciences from January 2018 to October 2020 were selected as the observation group,and 60 VA patients without HTN hospitalized during the same time were chose as the control group.By analysing patients age,classification of hypertension,hospital blood pressure pulse pressure(PP),brachial-ankle pulse wave velocity(baPWV),calcium(Ca),phosphorus(P)and magnesium(Mg),renin(REN),angiotensin converting enzyme(ACE),osteocalcin(OC),TCM type of syndromes,the influence of HTN on VA and related indicators of change will be known.Results:The syndromes of TCM showed that in VA patients with HTN,phlegm turbidity,blood stasis and qi deficiency were the most widespread,accounting for 53.33%,50%and 35%,respectively,and the syndromes of phlegm and blood stasis were the most widespread,accounting for 20%.Compared with the control group,vascular rigidity and serological indexes showed that baPWV and PP were significantly increased in the observation group.Compared with the observation group of different TCM syndrome types,baPWV and the serum Ca level increased in the Yang deficiency and blood stasis group,while the serum Mg level decreased in the qi and Yin deficiency group(P<0.05,P<0.01).Conclusion:Turbidity of phlegm and blood stasis are the main syndrome features of VA patients with HTN,and the syndromes are often intermingled with phlegm and blood stasis.In VA patients with HTN,the VA of Yang deficiency and blood stasis syndrome is the most serious,and its mechanism may be related to the disorder of calcium,phosphorus and magnesium metabolism in the body,which leads to vascular calcification and aging.3.Basic researchMechanistic research of Ang Ⅱ/NLRP3 inflammasome mediating the hypertensive rats with vascular agingObjective:By observing the different expression of Ang Ⅱ/NLRP3 inflammasome related signal path indexes in the spontaneously hypertensive rats(SHR)and control group rats,the possible effect mechanism of HTN on VA will be explored.Methods:There are three groups,Wistar control group(12 weeks),SHR model group(20 weeks)and WKY control group(20 weeks),with body weight of 180～200g.Blood pressure was measured by tail-sleeve method.Thoracic aorta and aortic arch were collected and stained by HE and Masson.The pathological morphology of aorta and the changes of vascular collagen fibers were observed under light microscope.Ca2+/Mg2+ATPase,Na+/K+ATPase activity detection,angiotensin Ⅱ(Ang Ⅱ),nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),smooth muscle 22-alpha(SM22α),matrix metalloproteinase 9(MMP-9),matrix metalloproteinases inhibitor 1(TIMP-1),plasma membrane Ca2+-ATPase 3(PMCA3)protein expression detection with western blot in thoracic aorta of rats.Results:HE and Masson staining showed that,in Wistar control rats the structure of the outer membrane was clear,the smooth muscle cells of the media were arranged regularly,and the intima of thoracic aorta and aortic arch were thinner.In WKY control rats,the smooth muscle cells of the media were still orderly,and the elastic fiber layers were orderly,while the intima of thoracic aorta and aortic arch were still smooth.In SHR model rats,the media was obviously thickened and unstructured,the smooth muscle cells layer were increased,the elastic fiber layers were twisted and thickened,the intimal surface of thoracic aorta and aortic arch was wrinkled,and the relative collagen contents were increased.Compared with Wistar control rats,AngⅡ protein,NLRP3 protein,MMP-9 protein and TIMP-1 protein expression were increased,while SM22αprotein expression was decreased in WKY control rats(P<0.05,P<0.01).The blood pressure of SHR model rats were significantly rised,and AngⅡ protein,NLRP3 protein,MMP-9 protein,TIMP-1 protein expression were increased,while Ca2+/Mg2+ATPase activity and SM22αexpression were decreased in SHR model rats(P<0.01).Compared with WKY control rats,the blood pressure of SHR model rats were significantly rised,and AngⅡ protein,NLRP3 protein,and MMP-9 protein expression were increased,while Ca2+/Mg2+ ATPase activity and SM22α expression were decreased in SHR model rats(P<0.05,P<0.01).Conclusion:With ageing,the degree of VA gradually increased.HTN can lead to vascular structural changes and vascular remodeling,thus affecting vascular function and inducing and aggravating VA.Its mechanism may be related to the increasing expression of AngⅡ protein,the activation of NLRP3 inflammasome,which induced inflammation,migration and proliferation of VSMCs furtherly,and resulted in phenotypic transformation,representative of the decreasing expression of SM22αprotein.Besides,MMP-9 protein expression was increased,ECM synthesis was increased.And Ca2+/Mg2+ATPase activity regulating intracellular Ca2+ homeostasis was decreased.