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基于血管解剖的椎间盘定位辅助穿刺构建机械损伤诱导的小鼠腰椎间盘退变模型

Vascular anatomy-based localization of intervertebral discs assisting needle puncture for constructing a mouse model of mechanical injury-induced lumbar intervertebral disc degeneration.

机构信息

School of Medicine, Xiamen University, Xiamen, Fujian, 361005, China; State Key Laboratory of Cellular Stress Biology, School of Medicine, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, 361102, China.

Xiamen Medical College, Xiamen, Fujian, 361005, China.

出版信息

Biochem Biophys Res Commun. 2022 Dec 17;634:196-202. doi: 10.1016/j.bbrc.2022.10.022. Epub 2022 Oct 7.

Abstract

Intervertebral disc degeneration (IDD) may be the primary cause of low back pain. Potential therapeutics for IDD must be validated in animal models, and their effectiveness quantified using functional metrics. Needle puncture of intervertebral discs (IVDs) has been used to induce IDD in mice and rats. Due to operational challenges, most animal IDD models are constructed using needle puncture of the caudal IVDs in mice, or by using larger animals, such as rats and rabbits. However, mouse IDD models involving lumbar IVD puncture are preferable because mice are genetically similar to humans and are the most commonly used transgenic animals, and because human IDD commonly affects the lumbar spine. We constructed a needle puncture-based mouse IDD model that relies on vascular anatomy to pinpoint lumbar IVDs. We evaluated the morphological and molecular changes in this model by using radiological, pathological, and immunostaining examinations. In our mechanical injury-induced IDD model, lumbar IVDs were accurately localized by injecting colored perfusates into the common iliac artery and vein, and right iliolumbar vein, which helped to visualize puncture positions, avoid neuromuscular injury, shorten the operation time, and decrease bleeding. Nucleus pulposus cells, defined by Krt19, and the disc height index gradually decreased after the surgery, and the degenerative effects peaked at 1 week. In conclusion, we established a mouse IDD model by performing precise puncture of lumbar IVDs via the ventral anterior approach assisted by vessel position. Our model effectively simulated the effects of IDD, and may serve as an efficient research tool.

摘要

椎间盘退变(IDD)可能是腰痛的主要原因。潜在的 IDD 治疗方法必须在动物模型中得到验证,并使用功能指标来量化其有效性。椎间盘内穿刺(IVD)已被用于在小鼠和大鼠中诱导 IDD。由于操作上的挑战,大多数动物 IDD 模型都是通过在小鼠尾部 IVD 进行针穿刺构建的,或者使用较大的动物,如大鼠和兔子。然而,涉及腰椎 IVD 穿刺的小鼠 IDD 模型更为可取,因为小鼠在遗传上与人类相似,是最常用的转基因动物,并且人类 IDD 通常影响腰椎。我们构建了一种基于针穿刺的小鼠 IDD 模型,该模型依赖于血管解剖结构来精确定位腰椎 IVD。我们通过放射学、病理学和免疫染色检查评估了该模型的形态和分子变化。在我们的机械损伤诱导的 IDD 模型中,通过将彩色灌注液注入髂总动脉和静脉以及右髂腰静脉,可以准确定位腰椎 IVD,从而有助于可视化穿刺位置,避免神经肌肉损伤,缩短手术时间并减少出血。手术后,Krt19 定义的髓核细胞和椎间盘高度指数逐渐减少,退行性变化在 1 周时达到高峰。总之,我们通过经腹前入路辅助血管定位对腰椎 IVD 进行精确穿刺,建立了一种小鼠 IDD 模型。我们的模型有效地模拟了 IDD 的作用,可能成为一种有效的研究工具。

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