葛根素抑制内质网应激减轻压力负荷引起小鼠心肌肥厚实验研究  

Puerarin mitigates pressure overload-induced cardiac hypertrophy by inhibiting endoplasmic reticulum stress in mice

作　　者：刘艳丽 董文婷 尚福军 冯海涛 郭锦 王锦 LIU Yanli;DONG Wenting;SHANG Fujun;FENG Haitao;GUO Jin;WANG Jin(Xi’an International Medical Center Hospital,Xi’an 710100,China)

机构地区：[1]西安国际医学中心医院,陕西西安710100 [2]西安市临潼区妇幼保健院,陕西西安710600

出　　处：《陕西医学杂志》2023年第2期123-127,共5页Shaanxi Medical Journal

基　　金：陕西省科技厅重点研发计划项目(2022SF-217);空军军医大学唐都医院创新基金资助项目(2017JCYJ007)。

摘　　要：目的:探讨葛根素(Pue)抑制内质网应激(ERS)对压力负荷下小鼠心肌肥厚的作用。方法:采用腹主动脉缩窄术(AAC)模拟压力负荷引起的心肌肥厚,将C57/bl小鼠随机分为四组(n=15):假手术组(Sham组)、葛根素对照组(Pue组)、腹主动脉缩窄术组(AAC组)和葛根素治疗AAC组(AAC+Pue组)。Pue组和AAC+Pue组术后腹腔注射50mg/(kg·d)Pue,Sham组和AAC组腹腔注射等量的0.9%氯化钠溶液,持续4周后,超声检测左室后壁厚度(LVPWd)、左室内径(LVId)和室间隔厚度(IVSd);测量心脏重量与体重比(HW/BW),WGA染色观察心肌细胞横截面积,Masson染色观察纤维化程度;RT-PCR检测ANP和Myh7的mRNA水平;Western blot检测PERK、CHOP和GRP78蛋白的表达。结果:Sham组和Pue组各指标间比较无统计学差异(均P>0.05);和Sham组相比,AAC组LVPWd、LVId和IVSd值增加(均P<0.01),HW/BW比增大,心肌横截面积和纤维化程度增加,ANP和Myh7的mRNA水平增加(均P<0.01),PERK和CHOP蛋白的表达增多,而GRP78表达降低(均P<0.01);和AAC组相比,AAC+Pue组LVPWd、LVId和IVSd值降低(均P<0.01),HW/BW比减小,心肌横截面积和纤维化程度降低,ANP和Myh7的mRNA水平减少(均P<0.01),PERK和CHOP蛋白的表达降低,而GRP78表达增加(均P<0.01)。结论:Pue可通过抑制内质网应激减轻压力负荷引起的心肌肥厚。Objective:To investigate the role of puerarin(Pue)in pressure overload-induced cardiac hypertrophy by inhibiting endoplasmic reticulum stress(ERS)in mice.Methods:Pressure overload-induced cardiac hypertrophy model was generated by using abdominal aortic coarctation(AAC)surgery.C57/bl mice were randomly divided into four groups with 15 mice in each:sham group(Sham group),Pue group(Pue group),abdominal aortic coarctation group(AAC group)and AAC treated with Pue group(AAC+Pue group).Pue group and AAC+Pue group were intraperitoneally injected with 50mg/(kg·d)Pue,Sham group and AAC group were intraperitoneally injected with 0.9%sodium chloride solution.After 4 weeks,left ventricular posterior wall thickness(LVPWd),left ventricular inner diameter(LVId)and ventricular septal thickness(IVSd)were measured by ultrasound;the heart weight to body weight ratio(HW/BW)was measured,the cross-sectional area of cardiomyocytes was observed by WGA staining,and the degree of fibrosis was observed by Masson staining;the mRNA levels of ANP and Myh7 were detected by RT-PCR;the expressions of PERK,CHOP and GRP78 proteins were detected by Western blot.Results:There was no significant difference between sham group and pue group(all P>0.05).Compared with Sham group,the AAC group had increased LVPWd,LVId and IVSd values,increased HW/BW ratio,increased myocardial cross-sectional area and degree of fibrosis,increased ANP and Myh7 mRNA levels,increased expression of PERK and CHOP proteins,and decreased GRP78 expression(all P<0.01).Compared with AAC group,the AAC Pue group had lower LVPWd,LVId and IVSd values,smaller HW/BW ratio,decreased myocardial cross-sectional area and degree of fibrosis,decreased ANP and Myh7 mRNA levels,decreased expression of PERK and CHOP proteins,and increased GRP78 expression(all P<0.01).Conclusion:Pue can alleviate pressure overload-induced cardiac hypertrophy by inhibiting endoplasmic reticulum stress.

关 键 词：葛根素 腹主动脉缩窄 内质网应激 小鼠 心肌肥厚 纤维化 

分 类 号：R541[医药卫生—心血管疾病]