基于AMPK/mTOR信号通路探讨潜阳育阴颗粒对高血压肾损伤的影响  

Effects of Qianyang Yuyin Granules on renal injury of spontaneously hypertensive rats based on AMPK/mTOR signal pathway

作　　者：马思齐 许骏尧 郑亚威 王艺璇 李海涛[1] 李婕 MA Si-qi;XU Jun-yao;ZHENG Ya-wei;WANG Yi-xuan;LI Hai-tao;LI Jie(College of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210000,China;The First Clinical Medical College,Nanjing University of Chinese Medicine,Nanjing 210000,China;Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210000,China)

机构地区：[1]南京中医药大学药学院,南京210000 [2]南京中医药大学第一临床医学院,南京210000 [3]南京中医药大学附属医院,南京210000

出　　处：《中华中医药杂志》2022年第6期3559-3563,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金青年科学基金项目(No.81904113);江苏省自然科学基金青年基金项目(No.BK20181095)。

摘　　要：目的:探讨潜阳育阴颗粒(QYYYG)对高血压肾损伤的治疗作用及相关分子机制。方法:动物实验以自发性高血压大鼠(SHR)为动物模型,Western Blot和免疫荧光检测各组大鼠肾脏组织自噬相关蛋白表达。细胞实验用血管紧张素Ⅱ(AngⅡ)处理足细胞,QYYYG含药血清干预,Western Blot检测足细胞p-AMPK/AMPK及自噬相关蛋白表达。AMPK抑制剂Compound C干预足细胞,检测p-AMPK/AMPK及自噬相关蛋白表达。结果:动物实验结果显示,与模型组比较,QYYYG能显著降低SHR肾脏组织中p-AMPK/AMPK及自噬相关蛋白Beclin、LC3Ⅱ/LC3Ⅰ的水平(P<0.01),同时显著上调P62和p-mTOR/mTOR的表达(P<0.01),其效果与阳性药缬沙坦类似。细胞实验结果显示,与空白对照组比较,AngⅡ能显著升高足细胞内p-AMPK/AMPK及自噬相关蛋白Beclin、LC3Ⅱ/LC3Ⅰ水平(P<0.01),降低P62(P<0.05)和p-mTOR/mTOR水平(P<0.01),而QYYYG含药血清能显著对抗AngⅡ的这种效应(P<0.01,P<0.05),其效果与缬沙坦和AMPK抑制剂Compound C相似,但对于p-AMPK/AMPK和Beclin的干预作用要弱于Compound C(P<0.05)。结论:QYYYG可以改善高血压肾损伤,其机制可能与抑制由AngⅡ经AMPK/mTOR通路引起的足细胞异常升高的自噬水平有关。Objective:To investigate the therapeutic effect and related molecular mechanism of Qianyang Yuyin Granules(QYYYG)on hypertensive renal injury.Methods:In animal experiments,spontaneous hypertension rats(SHR)were used as animal models.The expression of autophagy-related proteins in the kidneys of rats in each group was detected by Western Blot and immunofluorescence.In cell experiments,podocytes were treated with AngⅡand intervened with QYYYG-containing serum.Western Blot was used to detect the expressions of p-AMPK/AMPK and autophagy-related proteins in podocytes.AMPK inhibitor Compound C interfered with podocytes to observe the expression of p-AMPK/AMPK and autophagy-related proteins.Results:The results of animal experiments showed that compared with the model group,QYYYG could significantly reduce the levels of p-AMPK/AMPK and autophagy-related proteins Beclin,LC3Ⅱ/LC3Ⅰ(P<0.01)in the kidney tissue of SHR.Compared with the model group,QYYYG significantly up-regulated the expression of P62 and p-mTOR/mTOR(P<0.01),and its effect was similar to the positive drug valsartan.The results of cell experiments showed that compared with the blank control group,AngⅡcould significantly increase the levels of p-AMPK/AMPK and autophagy-related proteins Beclin,LC3Ⅱ/LC3Ⅰ(P<0.01),and decrease the levels of P62(P<0.05)and p-mTOR/mTOR(P<0.01)in podocytes.The QYYYG-containing serum was significantly resistant to this effect of AngⅡ(P<0.01,P<0.05),which was similar to that of valsartan and AMPK inhibitor Compound C,but the intervention effect of p-AMPK/AMPK and Beclin was weaker than that of Compound C(P<0.05).Conclusion:QYYYG can ameliorate hypertensive renal injury,and its mechanism may be related to the inhibition of abnormally elevated autophagy levels in podocytes caused by AngⅡthrough the AMPK/mTOR pathway.

关 键 词：潜阳育阴颗粒 高血压肾损伤 AMPK/mTOR 自噬 足细胞 

分 类 号：R285.5[医药卫生—中药学]