Denervation in Femoral Artery-Ligated Hindlimbs Diminishes Ischemic Recovery Primarily via Impaired Arteriogenesis.
Denervation in Femoral Artery-Ligated Hindlimbs Diminishes Ischemic Recovery Primarily via Impaired Arteriogenesis.
复制标题
股动脉结扎后肢的去神经主要通过动脉生成受损来减少缺血恢复
DOI：
10.1371/journal.pone.0154941
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Hu Z
中科院分区：
文献类型：
--
作者：
Cen Y;Liu J;Qin Y;Liu R;Wang H;Zhou Y;Wang S;Hu Z
目的：多因素调控动脉形成。周围神经在血管重建中起着重要作用，但周围神经在动脉形成中的作用尚不清楚。我们的研究探讨了后肢股动脉结扎后缺血恢复期间去神经支配对动脉生成的贡献。方法和结果SD大鼠随机分为正常对照组（NC）、后肢缺血组（HI）、后肢缺血去神经组（HID）和后肢单纯去神经组（HD）。术后第28天通过临床评估和胫骨前肌重塑评估后肢缺血恢复。在术后第0、3、7、14和28天通过激光多普勒成像测定血流。术后第7、28天行血管造影观察后肢侧支循环数目，行股薄肌免疫组化染色。术后第28天，通过计数胫骨前肌中的CD31阳性毛细血管来评估血管生成。术后第28天，HID组与其他3组相比缺血恢复受损，与HI组相比血流恢复受损。HID组侧支循环数和毛细血管密度低于HI组。HID组和HI组侧支直径均较NC组明显增大。但HID组管腔较HI组狭窄，管壁较HI组增厚。HID组侧支血管内膜增厚，由平滑肌细胞和内皮细胞组成。结论股动脉结扎后去神经支配通过灌注受损损害缺血恢复。灌注受损的可能机制是侧支数目减少、毛细血管密度降低和管腔狭窄，这损害了缺血恢复。本研究利用后肢缺血与失神经支配相结合的模型阐明了周围神经在动脉生成中的重要作用。
Aims Multiple factors regulate arteriogenesis. Peripheral nerves play a crucial role in vascular remodeling, but the function of peripheral nerves during arteriogenesis is obscure. Our study investigated the contribution of denervation to arteriogenesis during post-ischemic recovery from hindlimb femoral artery ligation. Methods and Results Sprague-Dawley rats were randomly allocated into four groups of normal control (NC), hindlimb ischemia (HI), hindlimb ischemia with denervation (HID) and hindlimb simple denervation (HD). Hindlimb ischemic recovery was assessed by clinical assessment and tibialis anterior muscle remodeling on day 28 post-surgery. Blood flow was determined by laser Doppler imaging on day 0, 3, 7, 14 and 28 post-surgery. Collateral number of hindlimb was observed by angiography and gracilis muscles were tested by immunostaining on day 7 and 28 post-surgery. Angiogenesis was accessed by counting CD31 positive capillaries in tibialis anterior muscles on day 28 post-surgery. Group HID showed impaired ischemic recovery compared with the other 3 groups and impaired blood flow recovery compared with group HI on day 28 post-surgery. The collateral number and capillary density of group HID were lower than group HI. The collateral diameter of both group HID and group HI significantly increased compared with group NC. However, the lumen diameter was much narrower and the vessel wall was much thicker in group HID than group HI. We also demonstrated that the thickened neointima of collaterals in group HID comprised of smooth muscle cells and endothelial cells. Conclusions Denervation of the ligated femoral artery in the hindlimb impairs ischemic recovery via impaired perfusion. The possible mechanisms of impaired perfusion are lower collateral number, lower capillary density and most likely narrower lumen, which damage ischemic recovery. This study illustrates the crucial role of peripheral nerves in arteriogenesis using a model combined ischemia with denervation in hindlimb.