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  • 标题:Involvement of Apoptosis Inhibitor of Macrophages in a Rat Hypertension Model with Nephrosclerosis: Possible Mechanisms of Action of Olmesartan and Azelnidipine
  • 本地全文:下载
  • 作者:Tadashi Uramatsu ; Tomoya Nishino ; Yoko Obata
  • 期刊名称:Biological and Pharmaceutical Bulletin
  • 印刷版ISSN:0918-6158
  • 电子版ISSN:1347-5215
  • 出版年度:2013
  • 卷号:36
  • 期号:8
  • 页码:1271-1277
  • DOI:10.1248/bpb.b12-00965
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:

    Stroke-prone spontaneously hypertensive (SHRsp) rats develop severe hypertension resulting in renal injury. We investigated apoptosis inhibitor of macrophages (AIM) expression in nephrosclerotic rats and the involvement of AIM in olmesartan (OLM)- and azelnidipine (AZN)-induced decreases in the number of macrophages infiltrating the kidney. We randomly assigned 20-week-old male SHRsp rats to receive one of the following substances every day for 12 weeks: water (vehicle), hydralazine (HYD), OLM, or AZN. Renal damage was assessed by Masson trichrome staining. Expressions of ED-1, AIM, and oxidized low-density lipoprotein (oxLDL) were immunohistochemically detected. Apoptosis was analyzed by terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) staining. All treatment groups showed significantly less renal interstitial fibrosis than the vehicle group. AZN and OLM groups had significantly fewer AIM-expressing cells than the HYD and vehicle groups. The ratios AIM-positive cells/ED-1-positive macrophages and TUNEL-positive cells/ED-1-positive macrophages in the AZN and OLM groups were lower and higher, respectively, than the the HYD and vehicle groups. oxLDL expression in the renal interstitium was significantly lower in treatment groups compared to vehicle group. OLM and AZN inhibited interstitial fibrosis progression in SHRsp rats by suppressing AIM expression in macrophages, followed by reducing the number of infiltrating macrophages.

  • 关键词:apoptosis; macrophage; nephrosclerosis; oxidized low-density lipoprotein
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