Study On The Role Of PLB-IRE1-XBP1 Pathway In Vascular Tissue Of Stress Induced Hypertensive Model Rats And The Intervention Of Traditional Chinese Medicine Huan Ya Le

Objective: To explore the role of PLB-IRE1-XBP1 pathway in the development of stress induced hypertension and the mechanism of intervention effect of traditional Chinese medicine Huan Ya Le.Methods:(1)72 SPF male Wistar rats were divided into normal group,negative control group,Huan Ya Le drug intervention group(high,medium and low dose)and positive control group(eplerenone),after 1 week of adaptive feeding.Rats in the normal group were fed without stimulation,and the remaining five groups of rats underwent compound stress stimulation for 12 weeks and were given corresponding vehicle or drug intervention;(2)RT-qPCR method was used to detect the mRNA expression levels of ace and at1 r genes in the thoracic aorta tissue of each group of rats;(3)Immunohistochemical method was used to localize and quantify the expression of XBP1 protein in the thoracic aorta of each group of rats;(4)Western blotting was used to detect the expression of PLB total protein,GRP78,XBP1,AT1 R protein and phosphorylation level of PLB and IRE1 protein in the thoracic aorta tissue of each group.Results:(1)Compared with the normal group,the systolic and diastolic blood pressures of the negative control group were significantly increased(P < 0.05);mRNA expression levels of ace and at1 r genes were significantly increased(P<0.05),The expression of PLB total protein,GRP78,XBP1 and AT1 R protein was up-regulated,PLB protein phosphorylation was down regulated,IRE1 protein phosphorylation was up regulated,XBP1 protein was mainly distributed in the nucleus of vascular tissue;(2)Compared with the negative controlgroup,the systolic and diastolic blood pressure of the Huan Ya Le high dose group rats was lower than that of the negative control group(P<0.05),and there was no significant difference compared with the normal group(P>0.05);compared with the negative control group,the Huan Ya Le high group,the expression level of ace、at1r gene mRNA was down-regulated(P<0.05),PLB total protein,GRP78,XBP1,AT1 R protein expression levels were significantly down-regulated(P<0.05),PLB protein phosphorylation level was significantly up-regulated(P<0.05),the phosphorylation level of IRE1 protein was significantly reduced(P<0.05),and the amount of XBP1 protein distributed in the nucleus of vascular tissue was reduced.Conclusion:(1)The level of PLB phosphorylation was down regulated in the thoracic aorta of hypertensive rats induced by complex stress factors,which caused endoplasmic reticulum stress and activated PLB-IRE1-XBP1 pathway;(2)The traditional Chinese medicine HuanYa Le may prevent endoplasmic reticulum stress and inhibit the activation of PLB-IRE1-XBP1 pathway by up regulating the phosphorylation level of PLB protein,so as to play a role in the prevention and treatment of hypertension.