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加味当归补血汤调控AMPK/SIRT3通路改善高血压肾病的机制研究 被引量:3

Research on the Mechanism of Modified Danggui Buxue Decoction for Regulating AMPK/SIRT3 Pathway to Improve Hypertensive Nephropathy
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摘要 目的:探究加味当归补血汤调控AMP活化蛋白激酶(AMPK)/沉默信息调节因子3(SIRT3)通路改善高血压肾病的机制。方法:以高盐饮食诱导建立高血压肾病大鼠,随机分为模型组、加味当归补血汤(15.6g/kg)组、CC(AMPK抑制剂,0.2mg/kg)组、加味当归补血汤(15.6g/kg)+CC(0.2mg/kg)组,每组12只,另取12只大鼠为对照组,以普通饮食喂养。经药物分组干预治疗后,测定大鼠尾动脉收缩压、舒张压;测定大鼠24h尿蛋白含量、血清肌酐(Scr)、血尿酸(SUA)水平;采用HE染色观察大鼠肾组织病理改变;采用酶标仪检测大鼠血清炎性介质活性氧(ROS)、白细胞介素-17(IL-17)、白细胞介素-6(IL-6)水平;采用免疫印迹法检测大鼠肾组织AMPK/SIRT3通路蛋白表达。结果:与对照组相比,模型组大鼠肾组织产生严重病理损伤,大鼠收缩压、舒张压、24h尿蛋白含量、Scr、SUA、血清ROS、IL-17及IL-6水平明显升高(P<0.05),肾组织p-AMPK/AMPK、SIRT3蛋白表达水平明显降低(P<0.05)。与模型组、加味当归补血汤+CC组分别相比,加味当归补血汤组大鼠肾组织病理损伤减轻,大鼠收缩压、舒张压、24h尿蛋白含量、Scr、SUA、血清ROS、IL-17及IL-6水平均降低(P<0.05),肾组织p-AMPK/AMPK、SIRT3蛋白表达水平均升高(P<0.05);CC组大鼠肾组织病理损伤加重,大鼠收缩压、舒张压、24h尿蛋白含量、Scr、SUA、血清ROS、IL-17及IL-6水平均升高(P<0.05),肾组织p-AMPK/AMPK、SIRT3蛋白表达水平均降低(P<0.05)。结论:加味当归补血汤可通过激活AMPK/SIRT3通路,抑制炎症发生及进展,降低高血压肾病大鼠血压,减轻肾组织病理损伤,改善大鼠肾功能。 Objective:To explore the mechanism of Modified Danggui Buxue Decoction in improving hypertensive nephropathy by regulating AMP-activated protein kinase(AMPK)/silent information regulator 3(SIRT3)pathway.Methods:Hypertensive nephropathy rats were induced by high-salt diet,and they were randomly divided into a model group,a Modified Danggui Buxue Decoction(0.4 g/kg)group,a CC(AMPK inhibitor,0.2 mg/kg)group,and a Modified Danggui Buxue Decoction(0.4 g/kg)+CC(0.2 mg/kg)group,with 12 rats in each group,another 12 rats were taken as the controlled group and fed with ordinary diet.After drug intervention treatment,the systolic blood pressure and diastolic blood pressure of the rat tail artery were measured.The 24 h urine protein content,serum creatinine(Scr),and blood uric acid(SUA)levels of rats were determined.HE staining was used to observe the pathological changes of rat kidney tissue.A microplate reader was used to detect rat serum inflammatory mediator reactive oxygen species(ROS),interleukin-17(IL-17),and interleukin-6(IL-6)levels.Western blotting was used to detect AMPK/SIRT3 pathway protein expression in rat kidney tissue.Results:Compared with the controlled group,the kidney tissue of the model group had severe pathological damage,the systolic blood pressure,diastolic blood pressure,24 h urine protein content,Scr,SUA,serum ROS,IL-17 and IL-6 levels were significantly increased(P<0.05),the expression levels of p-AMPK/AMPK and SIRT3 proteins in renal tissue were significantly reduced(P<0.05).Compared with the model group and the Modified Danggui Buxue Decoction+CC group respectively,the rats in the Modified Danggui Buxue Decoction group had less renal tissue pathological damage,the systolic blood pressure,diastolic blood pressure,24 h urine protein content,Scr,SUA,serum ROS,IL-17 and IL-6 levels were decreased(P<0.05),the expression levels of p-AMPK/AMPK and SIRT3 proteins in kidney tissue were increased(P<0.05).The pathological damage of kidney tissue in the CC group increased,the systolic blood pressure,diastolic blood pressure,24 h urine protein content,Scr,SUA,serum ROS,IL-17 and IL-6 levels were increased(P<0.05),the expression levels of p-AMPK/AMPK and SIRT3 proteins in kidney tissue were decreased(P<0.05).Conclusion:Modified Danggui Buxue Decoction can inhibit the occurrence and progression of inflammation by activating the AMPK/SIRT3 pathway,reduce the blood pressure of rats with hypertensive nephropathy,reduce the pathological damage of kidney tissue,and improve the renal function of rats.
作者 黎海翔 陈岳尧 周仕群 杨敏 刘旭和 LI Haixiang;CHEN Yueyao;ZHOU Qun(Department of Traditional Chinese Medicine,Danzhou People's Hospital,Danzhou Hai'nan 571799,China;Department of Nephrology,Danzhou People's Hospital,Danzhou Hai'nan 571799,China)
出处 《四川中医》 2022年第9期67-72,共6页 Journal of Sichuan of Traditional Chinese Medicine
关键词 加味当归补血汤 AMP活化蛋白激酶/沉默信息调节因子3通路 高血压肾病 Modified Danggui Buxue Decoction AMP-activated protein kinase/silencing information regulator 3 pathway Hypertensive nephropathy
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