广西师范大学学报(自然科学版) ›› 2020, Vol. 38 ›› Issue (1): 93-101.doi: 10.16088/j.issn.1001-6600.2020.01.012

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甲泼尼龙对单侧输尿管梗阻诱导的肾纤维化的影响

龙靖娴1, 潘毓敏2, 潘国律2, 黄容诚2, 彭艳2*   

  1. 1.广西师范大学生命科学学院,广西桂林541006;
    2.广西师范大学化学与药学学院,广西桂林541004
  • 收稿日期:2018-11-26 出版日期:2020-01-25 发布日期:2020-01-15
  • 通讯作者: 彭艳(1968—),女,辽宁锦州人,广西师范大学研究员。E-mail:pengyan630@aliyun.com
  • 基金资助:
    国家自然科学基金(81673473)

Effect of Methylprednisolone on Unilateral Ureteral Obstruction-induced Renal Fibrosis

LONG Jingxian1, PAN Yumin2, PAN Guolü2, HUANG Rongcheng2, PENG Yan2*   

  1. 1. College of Life Sciences, Guangxi Normal University, Guilin Guangxi 541006, China;
    2. School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin Guangxi 541004, China
  • Received:2018-11-26 Online:2020-01-25 Published:2020-01-15

摘要: 为探讨甲泼尼龙在小鼠肾纤维化中的作用,本文通过单侧输尿管梗阻(unilateral ureteral obstruction, UUO)实验建立肾纤维化模型。实验将25只雄性Balb/c小鼠随机分为假手术组、模型组、低剂量组、中剂量组、高剂量组。手术后第2天给药,14 d后,使用HE染色和Masson染色检测各组小鼠肾脏病理变化情况。Western blotting和IHC染色检测各组梗阻侧肾脏中Col-1、Col3A1、FN、α-SMA的表达情况以及TGF-β/Smad和NF-κB信号通路中蛋白的表达情况。结果显示UUO会导致小鼠肾间质纤维化,甲泼尼龙能显著减弱UUO小鼠肾间质细胞外基质Col-1、Col3A1、FN、α-SMA的生成,下调TGF-β/Smad和NF-κB信号通路中蛋白的表达。由此可知,甲泼尼龙对小鼠肾纤维化有明显的改善作用,它通过抑制TGF-β/Smad和NF-κB信号通路来减轻UUO诱导的肾纤维化。

关键词: 甲泼尼龙, UUO, TGF-β/Smad, NF-κB

Abstract: To investigate the role of methylprednisolone in renal fibrosis in mice,A renal fibrosis model was established by Unilateral Ureteral Obstruction (UUO) experiment. Twenty-five male Balb/c mice were randomly divided into sham operation group, model group, low dose group, medium dose group and high dose group. The drug was administered on the second day after the surgery, and 14 days later, renal pathological changes were detected by HE staining and Masson staining. Western blotting and IHC staining were used to detect the expression of Col-1, Col3A1, FN and α-SMA in the obstructed kidneys of each group and to detect the expression of TGF-β/Smad and NF-κB signaling pathways. The results showed that UUO can cause renal interstitial fibrosis. Methylprednisolone significantly attenuated the production of extracellular matrix Col-1, Col3A1, FN and α-SMA in UUO mice, and down-regulated expression of the protein in TGF-β/Smad and NF-κB signaling pathways. It can be seen that methylprednisolone has a significant improvement in renal fibrosis in mice, which reduces UUO-induced renal fibrosis by inhibiting TGF-β/Smad and NF-κB signaling pathways.

Key words: Methylprednisolone sodium succinate, UUO, TGF-β/Smad, NF-κB

中图分类号: 

  • R692
[1] OLAMIDE H M, RAQUEL D, THERESE D P, et al. Transforming growth factor-β protects against inflammation-related atherosclerosis in South African CKD patients[J]. International Journal of Nephrology, 2018, 2018: 1-11.
[2] YAMAGUCHI J, TANAKA T, NANGAKU M. Recent advances in understanding of chronic kidney disease[J]. F1000 Research, 2015, 4: 1-9.
[3] NAKAGAWA N, DUFFIELD J S. Myofibroblasts in fibrotic kidneys[J]. Current Pathobiology Reports, 2013, 1 (3): 189-198.
[4] 宗妍. 益气活血降浊方对肾间质纤维化TGF-β1/Smads/BMP-7信号转导通路影响的实验研究[D]. 北京:北京中医药大学, 2011.
[5] ZHANG Y, WANG S, LIU S, et al. Role of Smad signaling in kidney disease[J]. International Urology and Nephrology, 2015, 47 (12): 1965-1975.
[6] HUI Y L. Diverse Roles of TGF-β/Smads in renal fibrosis and inflammation[J]. International Journal of Biological Sciences, 2011, 7 (7):1056-1067.
[7] WANG K F, LIU H Y, WANG B, et al. Effects of intrathecal injection of methylprednisolone sodium succinate in acute spinal cord injury rabbits[J]. Chinese Journal of Surgery, 2013, 51 (5): 426.
[8] YAO Q M, LI PP, LIANG S M, et al. Methylprednisolone suppresses the Wnt signaling pathway in chronic lymphocytic leukemia cell line MEC-1 regulated by LEF-1 expression[J]. International Journal of Clinical and Experimental Pathology, 2015, 8 (7): 7921-7928.
[9] PORCARO F, PAGLIETTI M G, DIAMANTI A, et al. Anaphylactic shock with methylprednisolone sodium succinate in a child with short bowel syndrome and cow’s milk allergy[J]. Italian Journal of Pediatrics, 2017, 43(1):104.
[10]CHENG S, GAO W, XU X, et al. Methylprednisolone sodium succinate reduces BBB disruption and inflammation in a model mouse of intracranial haemorrhage[J]. Brain Research Bulletin, 2016, 127: 226-233.
[11]赵丽珂, 穆冰瑶, 周荣伟,等. 不同免疫抑制剂及甲泼尼龙对小鼠肺间质纤维化的疗效对比[J]. 中国临床保健杂志, 2017, 20 (5): 579-583.
[12]陈晓丽. 甲泼尼龙对哮喘患者气道纤维化转化因子的影响[J]. 临床合理用药杂志, 2017, 10(5): 39-40.
[13]SHAN G, ZHOU X, YUE X, et al. Astragalus membranaceus ameliorates renal interstitial fibrosis by inhibiting tubular epithelial-mesenchymal transition in vivo and in vitro[J]. Experimental and Therapeutic Medicine, 2016, 11 (5): 1611-1616.
[14]LEUS N G, ZWINDERMAN M R, DEKKER F J. Histone deacetylase 3 (HDAC 3) as emerging drug target in NF-κB-mediated inflammation[J]. Current Opinion in Chemical Biology, 2016, 33: 160-168.
[15]ZIYADEH F N. Mediators of diabetic renal disease: the case fortgf-Beta as the major mediator[J]. Journal of the American Society of Nephrology, 2004, 15(Sup 1): S55-S57.
[16]MENG X M, CHUNG A C K, LAN H Y. Role of the TGF-β/BMP-7/Smad pathways in renal diseases[J]. Clinical Science, 2013, 124 (3/4): 243-254.
[17]ZHANG L, ZHANG J, XU C, et al. Lefty-1 alleviates TGF-β1-induced fibroblast-myofibroblast transdifferentiation in NRK-49F cells[J]. Drug Design, Development and Therapy, 2015, 9: 4669-4678.
[18]NLANDU-KHODO S, NEELISETTY S, PHILLIPS M, et al. Blocking TGF-β and β-Catenin epithelial crosstalk exacerbates CKD[J]. Journal of the American Society of Nephrology, 2017, 28 (12): 3490-3503.
[19]CHEN L, YANG T, LU D W, et al. Central role of dysregulation of TGF-β/Smad in CKD progression and potential targets of its treatment[J]. Biomedicine and Pharmacotherapy, 2018, 101: 670-681.
[20]MENG X M, TANG P M, LI J, et al. TGF-β/Smad signaling in renal fibrosis[J]. Frontiers in Physiology, 2015, 6: 82.
[21]WISASTRA R, DEKKER F J. Inflammation, cancer and oxidative Lipoxygenase activity are intimately linked[J]. Cancers, 2014, 6 (3): 1500-1521.
[22]CHEN L F, MU Y J, GREENE W C. Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-κB[J]. The Embo Journal, 2014, 21(23): 6539-6548.
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