冬虫夏草提取物可减轻大鼠主动脉移植动脉硬化。
Cordyceps sinensis extracts attenuate aortic transplant arteriosclerosis in rats.
机构信息
Department of Transplantation Center, The First Affiliate Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, China.
出版信息
J Surg Res. 2012 Jun 1;175(1):123-30. doi: 10.1016/j.jss.2011.02.027. Epub 2011 Mar 21.
BACKGROUND
Transplant arteriosclerosis is a hallmark of chronic rejection and is still the major limiting factor affecting the success of long-term organ transplants. Development of transplant arteriosclerosis is refractory to conventional immunosuppressive drugs, and adequate therapy is not yet available. The aim of this study was to determine the role of Cordyceps sinensis extracts in reducing the formation of transplant arteriosclerosis in a rat aortic transplant model.
METHODS
Lewis rat aortic allografts were transplanted into Brown-Norway recipient rats. Recipients received 0.5, 1, 2, and 5 mg/kg of Cordyceps sinensis extracts (or control saline) daily via intragastric injection for 60 d. Grafts were harvested 60 d post-transplantation and intimal thickness determined microscopically following hematoxylin and eosin (H and E) staining and abdominal aorta protein profiles determined by Western blot analysis. Cellular localization was assessed by histology and immunohistochemistry and the serum analyzed for tumor necrosis factor alpha (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) by enzyme-linked immunosorbent assay (ELISA).
RESULTS
C. sinensis administration resulted in a significant reduction in neointimal formation (neointimal thickness 8.27 ± 1.95 μm [0.5 mg/kg], 3.69 ± 1.43 μm [1 mg/kg], 3.69 ± 1.43 μm [1 mg/kg], 3.69 ± 1.43 μm [1 mg/kg] versus 11.42 ± 2.67 μm [control]) and in the proliferative activity of vascular smooth muscle cells. In addition, localized expression of TNF-α and ICAM-1 in transplant aortas was characterized by immunohistochemistry and immunoblot analyses demonstrating that C. sinensis treatment significantly reduced TNF-α and ICAM-1 levels compared with levels observed in controls (P < 0.05). Serum TNF-α and ICAM-1 levels were significantly reduced in C. sinensis-treated animals compared with controls (P < 0.05).
CONCLUSION
C. sinensis treatment effectively reduced the formation of transplant arteriosclerosis in a rat aortic transplant model.
背景
移植性动脉硬化是慢性排斥反应的标志，仍是影响长期器官移植成功的主要限制因素。移植性动脉硬化的发展对常规免疫抑制剂治疗具有抗性，目前尚无充分的治疗方法。本研究旨在确定蛹虫草提取物在减少大鼠主动脉移植模型中移植性动脉硬化形成中的作用。
方法
将Lewis 大鼠主动脉同种异体移植物移植到 Brown-Norway 受体大鼠中。受体大鼠每天通过胃内注射接受 0.5、1、2 和 5mg/kg 的蛹虫草提取物（或对照生理盐水），持续 60 天。移植后 60 天收获移植物，通过苏木精和伊红（H 和 E）染色后显微镜下测定内膜厚度，并通过 Western blot 分析测定腹主动脉蛋白谱。通过组织学和免疫组织化学评估细胞定位，并通过酶联免疫吸附试验（ELISA）分析血清中肿瘤坏死因子-α（TNF-α）和细胞间黏附分子-1（ICAM-1）的水平。
结果
蛹虫草给药可显著减少新生内膜形成（新生内膜厚度 8.27 ± 1.95μm[0.5mg/kg]、3.69 ± 1.43μm[1mg/kg]、3.69 ± 1.43μm[1mg/kg]、3.69 ± 1.43μm[1mg/kg] 与 11.42 ± 2.67μm[对照]）和血管平滑肌细胞的增殖活性。此外，通过免疫组织化学和免疫印迹分析，移植主动脉中 TNF-α和 ICAM-1 的局部表达特征表明，与对照组相比，蛹虫草治疗显著降低了 TNF-α和 ICAM-1 的水平（P < 0.05）。与对照组相比，蛹虫草治疗动物的血清 TNF-α和 ICAM-1 水平显著降低（P < 0.05）。
结论
蛹虫草治疗可有效减少大鼠主动脉移植模型中移植性动脉硬化的形成。
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