Aerobic Exercise Mediated The Balance Of PI3K/Akt And MAPK Signaling Pathways To The Phenotype Switching Of VSMC In Spontaneously Hypertensive Rats

Objective: The phenotypic switching is thecritical initial steps whichis proliferation and migration of vascular smooth muscle. Meanwhile, proliferation and migrationof vascular smooth muscle are the common pathological foundationof hypertension, atherosclerosis and restenosis after angioplasty, etc cardiovascular disease.This study was to explore the influnence of age and aerobic exercise to SHR thoracic aortic smooth muscle phenotype transformation and PI3K/MAPK signal pathways between balance control.Methods: The first part: the selection of 1, 3, 9, 16 months each 12 male SHR and WKY, without any intervention, the rat tail artery noninvasive blood pressure measurement, anesthesia executed after each rat thoracic aortic experiment. 1. H&E staining: measure the wall thickness of each rat thoracic aorta;2. The immunohistochemical experiment: test each rat smooth muscle phenotypic marker protein alpha SM-actin, calponin, the expression of OPN and distribution;3. Western Blot protein imprinting method: detection of alpha SM-actin, calponin and the expression of OPN, signal protein p-Akt, Akt, e NOS,p-42/44 ERK,42/44 ERK, p-p38 MAPK, p38 MAPK.The second part: the 3 months of age(age section smooth muscle marker protein expression began to appear significant differences of age point) all 24 male SHR and WKY, grouping is as follows: quiet normal blood pressure in the control group(WKY-SED,n=12), blood pressure normal aerobic exercise group(WKY-EX, n=12), high blood pressure, quiet control group(SHR-SED,n=12), high blood pressure, aerobic exercise group(SHR-EX,n=12).Back before exercise artery noninvasive blood pressure measurement, after eight weeks of formal aerobics: each rat thoracic aortic experiment experimental measurements with the first part.Results: Based data: the first part:(1) In the rat of SHR and WKY SBP, MAP is on the rise along with the age growth, compared with the same age of WKY group, SHR group of SBP, DBP, MAP, HR significantly increased(P<0.01).(2) The H&E staining: the wall thickness of thoracic aorta is increasing, and in the nine months SHR and WKY appeared significant difference(P<0.05).(3) Immunohistochemistry and Western Blot experiments: 3 months beginning, WKY group and SHR group of alpha SM-actin, calponin protein expression was increased along with the age and cut, and OPN appear to rise, and 3 months SHR and WKY has significant difference(actin, calponin: P<0.05, OPN: P<0.01).p-Akt, the protein expression of eNOS quantity gradually decline with aging, p-ERK, p-p38 MAPK protein expression gradually increases with aging.The second part:(1)Compared with WKY-SED group,SBP,DBP,MAP,HR,were significantly higher in SHR-SED group(P<0.01),WKY-EX group SBP has significantly lowered(P<0.05).Compared with SHR-SED group,SBP,DBP(P<0.01)(P<0.05),MAP(P<0.05),HR(P<0.05)have significantly lowered inSHR-EX group.(2)The H&E staining:compared with WKY-SED group,SHR-SED group of thoracic aortic wall thickness increased significantly(P<0.01),WKY-EX group there was no significant difference;Compared with SHR-SED group,SHR-EX group of thoracic aortic wall thickness was significantly lower(P<0.05).(3)Immunohistochemistry and Western Blot experiments:compared with WKY-SED group,SHR-SED team alpha SM-actin,calponin protein expression level significantly lower,and OPN significantly higher(P<0.01),WKY-EX group there was no significant difference.Compared with SHR-SED group,SHR-EX group alpha SM-actin,calponin protein expression level is significantly increased,OPN is significantly lowered(P<0.05).Compared with WKY-SED group,SHR-SED group p-Akt(P<0.01),and eNOS(P<0.01)in amount of expression are significantly病理基础lowered,p-ERK(P<0.01)and p-p38 MAPK(P<0.01)are significant increased,In WKY-EX group,the p-Akt(P<0.05),and eNOS(P<0.01)in amount of expression showed a trend of increase.Compared with SHR-SED group,p-Akt(P<0.05),and eNOS(P<0.01)are significant increased inSHR-EX group,p-ERK(P<0.05)and p-p38 MAPK(P<0.05)are significantly lowered.Conclusions: Increased with age growing, thoracic aorta vascular smooth muscle contraction phenotypic marker protein gradually reduce, synthetic phenotype marker protein increased gradually in normal blood pressure rats and hypertension rats. The trend of increasing or decreasing is faster in Hypertensive rats.Aerobic exercise can inhibit the transformation from contraction phenotype to synthetic phenotype, and VSMC phenotype is decided by the balance of PI3K/Akt and MAPK signal pathway.