丹玉和脉颗粒调控Nrf2/HO-1信号通路改善高血压大鼠肾损伤的研究  

Investigating the effect of Danyu Hemai Granule(丹玉和脉颗粒)on renal injury in hypertensive rats via regulating the Nrf2/HO-1 signaling pathway

作　　者：王亚妮 符德玉[1] 李云凤 马玉龙 陈晓喆 曹博莹 周训杰[1] 桂明泰[1] 姚磊[1] 李建华[1] 王明珠 芦波[1] WANG Ya-ni;FU De-yu;LI Yun-feng;MA Yu-long;CHEN Xiao-zhe;CAO Bo-ying;ZHOU Xun-jie;GUI Ming-tai;YAO Lei;LI Jian-hua;WANG Ming-zhu;LU Bo(Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai200437,China)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院,上海200437

出　　处：《时珍国医国药》2025年第6期1001-1006,共6页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(82274262,82174130);国家中医药管理局高水平中医药重点学科建设项目(zyyzdxk-2023065);上海市医院中药制剂产业转化协同创新中心项目;上海中医药大学第十六批大学生创新活动计划项目(SHUTCM2023287);上海市白玉兰人才计划浦江项目(24PJD113)。

摘　　要：目的观察丹玉和脉颗粒对自发性高血压大鼠(SHR)的疗效,基于Nrf2/HO-1信号通路探讨中药的可能保护机制。方法将18只5周龄雄性SHR适应性喂养一周后随机分为SHR组(饮用水灌胃)、丹玉和脉颗粒组(丹玉和脉颗粒每天42g生药·kg^(-1)灌胃)、缬沙坦组(缬沙坦每天30 mg·kg^(-1)灌胃),每组6只,6只周龄/性别相匹配的WKY大鼠饮用水灌胃用作对照。各组大鼠灌胃1次/d,连续10周,每2周测量血压。第10周末取大鼠肾脏组织,HE及Masson染色观察大鼠肾组织病理改变。Western blot检测大鼠肾组织Nrf2、HO-1、GPX4蛋白表达。结果与WKY组相比,SHR组大鼠收缩压显著升高(P<0.001),肾小球体积增大,肾小管上皮细胞空泡化,胶原纤维增生明显。SHR组大鼠肾组织Nrf2、HO-1、GPX4蛋白表达显著下降(P<0.001)。与SHR组相比,丹玉和脉颗粒可降低大鼠血压(P<0.05),减轻肾小管空泡化,改善胶原纤维增生,肾组织中Nrf2、HO-1表达显著增加(P<0.05)。结论丹玉和脉颗粒能降低SHR收缩压,减轻肾脏病理损害与氧化应激损伤,其作用机制可能与调控Nrf2/HO-1通路有关。Objective To observe the therapeutic effect of Danyu Hemai Granule(丹玉和脉颗粒,DYHMG)in spontaneously hypertensive rats(SHR)and explore its possible protective mechanism in Chinese herbal medicine(CHM)based on the Nrf2/HO-1 signaling pathway.Methods Eighteen 5-week-old male SHRs were adaptively fed for one week and then randomly assigned to three groups:the SHR group(gavage with distilled water),the DHG group(gavage with DHG at 42 g crude drug·kg~(-1)per day)and the valsartan group(gavage with valsartan at 30 mg·kg~(-1)per day),with 6 rats in each group.Six age and sex matched WKY rats gavaged with distilled water served as the control.All rats were gavaged once a day for 10 weeks,with blood pressure measured every 2 weeks.At the end of the 10th week,the renal tissues were collected.Pathological changes in the renal tissues were observed by HE and Masson staining.Western blot(WB)was used to detect the protein expressions of Nrf2,HO-1,and GPX4 in the renal tissues.Results Compared with the WKY group,the SHR group showed significantly elevated systolic blood pressure(P<0.001),enlarged glomerular volume,vacuolization of renal tubular epithelial cells,and marked collagen fiber hyperplasia.Protein expressions of Nrf2,HO-1 and GPX4 in the renal tissues of rats in the SHR group were significantly decreased(P<0.001).Compared with the SHR group,DYHMG could lower the blood pressure(P<0.05),alleviated renal tubular vacuolization,ameliorated collagen hyperplasia,and significantly increased Nrf2 and HO-1 expression in the renal tissues(P<0.05).Conclusion DYHMG can reduce systolic blood pressure in SHRs,mitigate renal pathological damage and oxidative stress injury,and its mechanism may be associated with the regulation of the Nrf2/HO-1 pathway.

关 键 词：丹玉和脉颗粒 高血压 肾脏损伤 核转录因子E2相关因子2/血红素加氧酶-1通路 氧化应激 

分 类 号：R285.5[医药卫生—中药学]