Department of Internal Medicine, Section of Cardiovascular Medicine, Yale University, New Haven, CT 06519, USA.
J Vasc Interv Radiol. 2011 Oct;22(10):1437-46. doi: 10.1016/j.jvir.2010.12.039. Epub 2011 Apr 3.
To develop an interventional hindlimb ischemic model and compare its angiogenic effect versus surgical ligation (SL) and excision of the femoral artery in rats treated with transplantation of bone marrow mononuclear cells (MNCs) as an angiogenic stimulator.
Forty-eight Lewis rats randomly received interventional embolization (IE) with hydrogel wire or SL and excision of the right femoral artery. Rodents were intraarterially transplanted with 1.5 × 10(7) MNCs in 500 μL medium from 24 isogenic donor rats. Functional and structural recovery was evaluated by laser Doppler imaging (LDI), cytokine/chemokine assay, and histologic staining.
In vivo microscopic images showed significantly dilated vasa vasorum around the embolized segment of the right femoral artery at 3 days compared with disorganized tissue structure in the SL group. However, the LDI index was significantly higher in the SL group at 3 days compared with the IE group. LDI did not significantly differ between the two groups at 2 weeks after transplantation. Cytokine assay showed higher levels of interleukin (IL)-1α and IL-18 in the SL group; the IE group had higher levels of interferon-γ, IL-6, IL-13, and granulocyte colony-stimulating factor. Histologic examination demonstrated inflammatory infiltration near the incision within nerve fibers with dilated capillaries, showing nerve degeneration in the SL group. At 2 weeks, histologic analysis demonstrated massive scarring under the skin spreading into the musculature in the SL group.
A minimally invasive hindlimb ischemia model has been successfully developed that preserves tissue integrity and minimizes inflammation and confounding factors in the early stages of angiogenesis and arteriogenesis.
建立一种介入性后肢缺血模型，并比较其与手术结扎（SL）和切除股动脉后，在接受骨髓单核细胞（MNC）移植作为血管生成刺激剂治疗的大鼠中的血管生成效果。
48 只 Lewis 大鼠随机接受水凝胶丝介入栓塞（IE）或 SL 及右侧股动脉切除术。将 1.5×10(7)个 MNCs 移植到 500μL 培养基中，通过动脉内途径从 24 只同基因供体大鼠中输注。通过激光多普勒成像（LDI）、细胞因子/趋化因子测定和组织学染色评估功能和结构恢复。
体内显微镜图像显示，与 SL 组紊乱的组织结构相比，右股动脉栓塞段周围的血管生成腔明显扩张。然而，在 3 天时，SL 组的 LDI 指数明显高于 IE 组。移植后 2 周时，两组之间的 LDI 无显著差异。细胞因子测定显示 SL 组白细胞介素（IL）-1α和 IL-18 水平较高；IE 组干扰素（IFN）-γ、IL-6、IL-13 和粒细胞集落刺激因子水平较高。组织学检查显示 SL 组切口附近神经纤维内有炎症浸润和扩张的毛细血管，显示神经变性。在 2 周时，组织学分析显示 SL 组皮肤下有大量瘢痕形成，向肌肉扩散。
成功建立了一种微创后肢缺血模型，在血管生成和动脉生成的早期阶段保持组织完整性，最大限度地减少炎症和混杂因素。
