金丝桃苷调节AMPK/mTOR/ULK1信号通路对肾病综合征大鼠自噬反应的影响
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邢台市人民医院

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Influence of hyperoside on autophagy in rats with nephrotic syndrome by regulating AMPK/mTOR/ULK1 signaling pathway
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Xingtai Peoples Hospital

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    摘要:

    目的 探究金丝桃苷(Hyp)对肾病综合征(NS)大鼠肾脏自噬及AMPK/mTOR/ULK1通路的影响。方法 32只6周龄SD大鼠分为正常组(N组)、NS组、Hyp组(60 mg/kg Hyp)、Hyp AMPK抑制剂组(Hyp CC组)(60 mg/kg Hyp 0.2 mg/kg CC),每组8只。给药结束后,全自动分析仪检测24 h尿液总蛋白(UTP)、血尿素氮(BUN)、血清肌酐(Scr)和白蛋白(ALB)水平;HE染色和TEM观察观察肾病理形态和超微结构;Western blot检测肾中自噬、足细胞及AMPK/mTOR/ULK1通路蛋白表达;免疫荧光染色观察自噬体和足细胞的定位。结果 相比于N组,NS组肾小球体积变大、肾小管萎缩或部分消失、基底膜增厚;UTP、BUN、Scr、基底膜厚度、足突宽度及p-AMPK/AMPK比值显著增加(P<0.05),ALB、LC3-Ⅱ/Ⅰ、Beclin-1、Atg5、Atg7、NPHS2蛋白水平、NPHS2、Beclin-1相对荧光强度及p-AMPK/AMPK、p-ULK1/ULK1比值显著降低(P<0.05)。相比于NS组,Hyp治疗可改善肾小球形态,降低UTP、BUN、Scr、基底膜厚度、足突宽度及p-AMPK/AMPK比值(P<0.05),增加ALB、LC3-Ⅱ/Ⅰ、Beclin-1、Atg5、Atg7、NPHS2蛋白水平、NPHS2、Beclin-1相对荧光强度及p-AMPK/AMPK、p-ULK1/ULK1比值(P<0.05)。AMPK抑制剂组CC能减弱Hyp的促自噬和保肾脏作用。结论 Hyp可能通过激活AMPK/mTOR/ULK1通路促进肾细胞自噬活性,减轻NS大鼠的足细胞损伤等肾脏病变。

    Abstract:

    Objective To investigate the influences of hypericin (Hyp) on renal autophagy and AMPK/mTOR/ULK1 pathway in nephrotic syndrome (NS) rats. Methods Thirty-two 6-week-old SD rats were grouped into normal group (N group), NS group, Hyp group (60 mg/kg Hyp), Hyp AMPK inhibitor group (Hyp CC group) (60 mg/kg Hyp group) 0.2 mg/kg CC), 8 per group. After administration, an automatic analyzer was applied to detect the levels of 24-h urine total protein (UTP), blood urea nitrogen (BUN), serum creatinine (Scr) and albumin (ALB); HE staining and TEM observation were applied to observe renal pathological morphology and ultrastructure; Western blot was applied to detect the expression of autophagy, podocyte and AMPK/mTOR/ULK1 pathway proteins in kidney; immunofluorescence staining was applied to visualize the localization of autophagosomes and podocytes. Results Compared with the N group, the glomerular volume of the NS group increased, the renal tubules atrophied or partially disappeared, and the basement membrane thickened; UTP, BUN, Scr, basement membrane thickness, foot process width and the ratio of p-AMPK/AMPK were obviously increased (P<0.05), the protein levels of ALB, LC3-II/I, Beclin-1, Atg5, Atg7, NPHS2, the relative fluorescence intensity of NPHS2 and Beclin-1, and the ratios of p-AMPK/AMPK and p-ULK1/ULK1 were obviously decreased (P<0.05). Compared with NS group, Hyp treatment was able to improve glomerular morphology, decrease UTP, BUN, Scr, basement membrane thickness, foot process width and ratio of p-AMPK/AMPK (P<0.05), increase protein levels of ALB, LC3-II/I, Beclin-1, Atg5, Atg7, NPHS2, the relative fluorescence intensity of NPHS2 and Beclin-1 and the ratios of p-AMPK/AMPK and p-ULK1/ULK1 (P<0.05). AMPK inhibitor group CC could attenuate the autophagy-promoting and kidney-protecting effects of Hyp. Conclusion Hyp may enhance the autophagy activity of renal cells and attenuate renal pathology such as podocyte injury in NS rats by activating the AMPK/mTOR/ULK1 pathway.

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  • 收稿日期:2022-12-20
  • 最后修改日期:2023-09-14
  • 录用日期:2023-11-03
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