摘要
目的基于circNRG-1/miR-193b-5p/NRG-1轴探讨肥胖性高血压发生的分子生物学机制。方法90只SD大鼠采用随机数字表法将其分为空白对照组(n=30)、肥胖性高血压组(n=30)、NRG-1阻断剂组(n=30)三组,检测大鼠的血压、体质量、Lee系数、脂肪系数、血清中三酰甘油和总胆固醇水平及胸主动脉中circNRG-1/miR-193b-5p/NRG-1的表达;微阵列分析肥胖性高血压大鼠中circNRG-1的表达;双荧光素酶分析circNRG-1与miR-193b-5p的靶向关系。结果微阵列结果发现,在空白对照组和肥胖性高血压组之间有382个circRNAs的差异表达,其中235个表达上调,147个表达下调(>2倍);与空白对照组比较,肥胖性高血压组的MMU-CircRNA-42742(其父本基因为NRG-1)上调,肥胖性高血压组大鼠的收缩压、体质量、Lee系数、脂肪系数、血清中三酰甘油、总胆固醇、胸主动脉中NRG-1、circNRG-1、miR-193b-5p的mRNA表达均升高,且血管壁增生,血管中膜增厚;与肥胖性高血压组比较,NRG-1阻断剂组大鼠的收缩压、体质量、Lee系数、脂肪系数、血清中三酰甘油、总胆固醇、胸主动脉中NRG-1、circNRG-1、miR-193b-5p的mRNA表达均降低,且血管出现重构现象。结论肥胖性高血压大鼠中circNRG-1、NRG-1表达上调,miR-193b-5p表达下调,阻断NRG-1后肥胖性高血压大鼠症状有所改善,circNRG-1/miR-193b-5p/NRG-1轴可能是治疗肥胖性高血压的潜在靶点。
Objective To explore molecular biological mechanism of Obesity Hypertension based on circNRG-1/miR-193b-5p/NRG-1 Axis.Methods 90 SD rats were randomly divided into three groups:control group(n=30),obese hypertension group(n=30)and NRG-1 blocker group(n=30).Blood pressure,body weight,Lee coefficient,fat coefficient,serum triglyceride and total cholesterol levels and the expression of circNRG-1/miR-193b-5p/NRG-1 in thoracic aorta were measured,and the expression of circNRG-1 in obese hypertensive rats was analyzed by microarray,the targeting relationship between circNRG-1 and miR-193b-5p was analyzed by double luciferase.Results The results of microarray showed that there were 382 circRNAs differentially expressed between the blank control group and the obese hypertension group,of which 235 were up-regulated and 147 were down-regulated(>2 times).Compared with the blank control group,the MMU-CircRNA-42742(whose paternal gene was NRG-1)was up-regulated in the obese hypertension group.Compared with the blank control group,the MMU-CircRNA-42742(paternal gene NRG-1)was up-regulated in the obese hypertension group.Compared with the blank control group,the systolic blood pressure,body weight,Lee coefficient,fat coefficient,serum triglyceride,total cholesterol,and the mRNA expression of NRG-1,circNRG-1 and miR-193b-5p in thoracic aorta of obese hypertensive rats all increased,and the vascular wall was proliferated and the intima was thickened.Compared with obese hypertension group,systolic blood pressure,body weight,Lee coefficient,fat coefficient,serum triglyceride,total cholesterol,mRNA expression of NRG-1,circNRG-1 and miR-193b-5p in thoracic aorta decreased in NRG-1 blocker group,and vascular remodeling appeared.Conclusion The expression of circNRG-1 and NRG-1 is up-regulated and the expression of miR-193b-5p is down-regulated in obese hypertensive rats.After blocking NRG-1,the symptoms of obese hypertensive rats improve,so circNRG-1/miR-193b-5p/NRG-1 axis may be a potential target for the treatment of obese hypertensi
作者
王玉孝
李俊
汪生毅
白雪莲
李春梅
高登峰
Wang Yuxiao;Li Jun;Wang Shengyi(Dept of Cardiovascular Medicine,Qinghai Provincial Red Cross Hospital,Xining 810000;Dept of Cardiovascular Medicine,Qinghai Children′s Hospital,Xining 810000)
出处
《安徽医科大学学报》
CAS
北大核心
2021年第9期1367-1373,共7页
Acta Universitatis Medicinalis Anhui
基金
国家自然科学基金(编号:81570382)。
