摘要
目的探讨中药复方缓压乐(HYL)对应激性高血压(Stress induced hypertension,SIH)大鼠血管组织内质网应激(Endoplasmic reticulum stress,ERS)肌醇需求因子1(Inositol-requiring enzyme 1,IRE1)信号通路的影响。方法取30只Wistar大鼠随机分为模型组,高、中、低剂量药物干预组和阳性对照组,每组6只,另取6只为正常组(不建模)。除正常组以外的大鼠进行间断足底电、噪声刺激12周,建立SIH模型;在造模期间,模型组大鼠每天用蒸馏水灌胃,药物干预组大鼠每天灌胃不同剂量的HYL,阳性对照组大鼠每天灌胃依普利酮溶液。造模期间检测各组大鼠尾动脉收缩压和舒张压;用RT-qPCR检测大鼠胸主动脉组织ace、at1r基因的mRNA表达水平;用IHC法对胸主动脉组织X盒结合蛋白1(X-box binding protein-1,XBP1)的表达进行定位和定量;用Western blot检测血管组织总受磷蛋白(phospholamban,PLB)、p-PLB、p-IRE1及XBP1相对表达水平。结果(1)与正常组相比,模型组、中及低剂量组大鼠收缩压和舒张压明显升高(P<0.05),高剂量组与阳性对照组无明显变化(P>0.05)。(2)与正常组相比,模型组大鼠胸主动脉组织ace、at1r基因mRNA表达水平均上调;与模型组相比,高剂量组和阳性对照组中ace、at1r基因mRNA表达水平均下调(P<0.05)。(3)与正常组相比,模型组和低剂量组大鼠胸主动脉组织血管平滑肌细胞中XBP1蛋白总表达量明显增多(P<0.05);相对于模型组,高剂量组和阳性对照组中XBP1蛋白染色淡、阳性表达低,且总表达量明显减少(P<0.05)。(4)相较于正常组,模型组、中及低剂量组总PLB、p-IRE1、XBP1表达量均明显上调,p-PLB表达量明显下调(P<0.05);与模型组相比,高剂量组及阳性对照组中总PLB、p-IRE1、XBP1表达量均明显下调,而p-PLB表达量明显上调(P<0.05)。结论HYL通过调节SIH大鼠血管组织PLB的活性、且抑制IRE1信号通路相关蛋白表达水平,降低血管组织ERS,从而发挥降低血压的�
Objective To investigate the effects of Chinese medicine Huan Ya Le(HYL)on inositol-requiring enzyme 1(IRE1)signaling pathway of endoplasmic reticulum stress in stress induced hypertension(SIH)rats.Methods 30 Wistar rats were randomly divided into a model group,a high,medium,and low dose drug intervention group,and a positive control group,with 6 rats in each group.The other 6 rats were selected as the normal group(without modeling).Except for the normal group,the rats were subjected to intermittent plantar electrical and noise stimulation for 12 weeks to establish SIH model.During modeling,rats in the model group were intragastric with distilled water daily,and the rats in drug intervention group were intragastric with different doses of HYL daily,the rats in positive control group were intragastric with eplerenone solution every day.Systolic and diastolic blood pressure of tail artery were detected during modeling.The mRNA expression levels of ace and at1r gene in rat thoracic aorta tissue were detected by RT-qPCR.Immunohistochemistry was used to localize and quantify the expression of X-box binding protein-1(XBP1)in the thoracic aorta of rats.Western blot was used to detect the relative expression levels of total phospholamban(PLB),p-PLB,p-IRE1 and XBP1 in vascular tissues.Results(1)Compared with normal group,systolic and diastolic blood pressure were significantly increased in model group,medium and low dose groups(P<0.05),while there were no significant changes in high dose group and positive control group(P>0.05).(2)Compared with the normal group,the mRNA expression levels of ace,at1r genes in thoracic aorta tissues of rats in model group were up-regulated.Compared with the model group,ace,at1r genes in the high dose group and positive control group were down-regulated(P<0.05).(3)Compared with normal group,the total expression of XBP1 protein in vascular smooth muscle cells of thoracic aorta tissue of rats in model group and low dose group were significantly increased(P<0.05).Compared with model group,high
作者
纳菲沙·卡德尔
阿依西布·萨吾提
钟莉
库热西·玉努斯
Nafeisha Kadeer;Ayixibu Sawuti;ZHONG Li;Kurexi Yunusi(School of Basic Medical Sciences,Urumqi 830017,China;College of Pharmacy,Xinjiang Medical University,Urumqi 830017,China;Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases,Urumqi 830054,China;Core Facilities,Zhejiang University School of Medicine,Hangzhou 310000,China;Uygur Medical College,Xinjiang Medical University,Urumqi 830017,China)
出处
《新疆医科大学学报》
CAS
2023年第4期447-452,共6页
Journal of Xinjiang Medical University
基金
新疆维吾尔自治区自然科学基金(2020D01C161)。
关键词
应激性高血压
内质网应激
中药复方缓压乐
肌醇需求因子1信号通路
慢性应激
stress induced hypertension
endoplasmic reticulum stress
traditional Chinese medicine(TCM)Huan Ya Le(HYL)
inositol-requiring enzyme 1 pathway
chronic stress
