| Background and Objective: Hypertension is one of the most common chronic diseases in the population.Compared with the large number of patients,an effective control rate has not been reached yet.As a result,the huge economic and social burden have been brought by the adverse consequences.As a disease that affects the whole body system,the adverse consequences caused by hypertension mainly include the damage of blood vessels,heart,brain,kidney and other target organs,the most important of which is to cause the reconstruction of myocardium,and then lead to cardiac insufficiency.There are many ways for hypertension to cause myocardial remodeling,including hemodynamic factors such as left ventricular concentric hypertrophy caused by pressure overload,as well as non hemodynamic factors such as neurohumoral effects and inflammatory factors.In addition,a variety of diseases,including coronary heart disease,myocardial infarction,diabetic myocardial injury,autoimmune cardiomyopathy and other diseases which can lead to myocardial remodeling,are involved in endoplasmic reticulum stress(ERs)response.This suggests that ERS response is related to myocardial remodeling,and the remodeling of myocardium caused by hypertension is also accompanied by ERS response,but which protein related to ERS is not very clear.ERS mainly works through three endoplasmic reticulum stress signaling pathways: double stranded RNA dependent protein kinase like ER kinase(PERK)pathway,inositol requiring enzyme 1(IRE-l)pathway and activating transcription factor 6(ATF6)pathway.In general,the transmembrane receptors ATF6,perk and IRE1 of the three ERS signaling pathways bind to the ER chaperone GRP78.When ER stress occurs,GRP78 dissociates from transmembrane receptor and initiates unfolded protein response(UPR),which further promotes the cytoprotective effect of ERS in the early stage.CHOP protein is a molecule of apoptosis signal induced by ERS,which plays an important role in apoptosis and can also reflect the level of apoptosis.Caspase 12 is a downstream regulatory protein of apoptosis response.When Caspase 12 is activated.,Caspase 9-Caspase 3 can be further activated to mediate apoptosis.Aerobic exercise,as an important activity to improve people's life style,has always been effective in the prevention of cardiovascular diseases.But whether it can reduce blood pressure and improve myocardial remodeling caused byhypertension,and what factors are related to this improvement,there is no clear conclusion.By using the spontaneously hypertensive rats(SHR)as human hypertension,the experiment of aerobic exercise was designed to analyze the myocardial structure and the effect of aerobic exercise on SHR.At the same time,measure the expression of GRP78,CHOP and Caspase12 protein in myocardial tissue of each group,to explore the relationship between the effects of aerobic exercise on myocardial remodeling and ERS in hypertensive rats.Materials and methods: SHR rats(n = 6)were used as aerobic exercise group(SHR-E),and SHR rats(n = 6)were used as resting control group(SHR-R),WKY(n = 6)as a non hypertensive non exercise control group,rats in SHR-E group were given moderate intensity aerobic exercise for 8 weeks(the speed was set at 2m / min,reaching to ?55-65% of the maximum aerobic speed,60 min / day,for 5 days / week).The blood pressure,heart rate and other vital signs of rats in each group were recorded simultaneously before and after the experiment,and then the rats were executed painlessly.The myocardial tissue was taken,paraffin section was made,and the content of collagen fiber in each group was compared with Masson staining.The expression of GRP78,CHOP and Caspase12 protein in myocardial cells in each group was compared with immunohistochemical method,and the expression of GRP78,CHOP and Caspase12 protein in myocardial cells in each group was compared with Western blot method.Results: Compared with the baseline,after 8 weeks of aerobic exercise,1)in terms of blood pressure,both the SHRs had a significant increase.Besides,the increase of SHR-E group was less than SHR-R group in systolic blood pressure(P < 0.05);in terms of heart rate,SHR-E group had a increase;in terms of the ratio of left ventricle to body weight,there was no significant difference between the groups(P > 0.05).2)Pathological changes of collagen content in myocardial tissue: the collagen content in SHR-R group was the most,followed by that in SHR-E group,and that in WKY group was the least(P< 0.05).3)Immunohistochemical results: the expression of GRP78 protein in WKY group was the least(AOD value 0.139 ± 0.078),and that expressed in SHR-E group was the most(AOD value 2.491 ± 0.578).The expression of GRP78 protein in SHR-R group was stated between the two groups above(AOD value 0.139 ± 0.078).The AOD value of each group was statistically different(P < 0.05).The expression level of CHOP protein inWKY group was the lowest(AOD 0.31 ± 0.302),SHR-R group was the highest(AOD4.49 ± 0.613),SHR-E was stated between the two groups above(AOD 2.28 ± 0.404),AOD value of each group was statistically significant(P < 0.05).The expression of Caspase12 protein in WKY group was the lowest(AOD 1.15 ± 0.159),SHR-R group was the highest(AOD 3.87 ± 0.435),and SHR-E group was stated between the two groups above(AOD 2.41 ± 0.474).The results of Western blot were consistent with the results of immunohistochemistry,but the content of CHOP protein in WKY group and SHR-E group,as well as the content of Caspase12 protein in SHR-R group and SHR-E group did not show statistically significant difference.Conclusion: Hypertension can lead to the increase of collagen fiber content as well as the expression of ERS related proteins.Aerobic exercise,to some extent,can inhibit the increase of collagen fibers,and improving myocardial remodeling.At the same time,the adverse reaction of ERS can be inhibited,including increasing the expression of protective factor GRP78,reducing the expression of damaging factors CHOP and Caspase12,slowing down the apoptosis of myocardial cells.Besides,aerobic exercise can improve blood pressure,especially the rise of systolic blood pressure and the heart damage caused by it. |
PDF Full Text Request