动物造模,药效评价,椎间盘脱出 z-bio 2024-07-18 572

　　The modeling mechanism involves the intervention of external experimental methods to cause sustained changes in the weight-bearing capacity, overload, physical damage, or destruction of the normal anatomical structure of the intervertebral disc, resulting in intervertebral disc degeneration and the occurrence of intervertebral disc herniation symptoms.

　　The experimental induction method is generally divided into stress type and structural type.

　　1. The animal model of stress-induced intervertebral disc herniation adopts the dynamic axial compression method, and different intensities, frequencies, and durations of axial loads are used to induce degenerative changes in the animal intervertebral disc. Dynamic pressure can be applied to the fixed tail of rats through mechanical devices for 2 hours per day, which can cause stress redistribution in the intervertebral disc and subsequently trigger local biological reactions. When the external force continues to exceed the expansion pressure of the intervertebral disc, the volume of the nucleus pulposus decreases, and then the pressure is redistributed to the inner fibrous ring, causing intervertebral disc herniation.

　　A common model also includes simulating intervertebral disc fusion in rabbits, which exhibits similar pathological and physiological changes as human L4-L5 and L7-S1 intervertebral disc degeneration. Three months after surgery, the formation of collagen bundles within the fibrous ring of the rabbit intervertebral disc and the destruction of the normal arrangement structure can be observed. Six months after surgery, the fibrous ring structure of the rabbit was further damaged. Nine months after surgery, the fibrous ring of the rabbit was replaced by fibrous tissue with disordered structural arrangement.

　　A mouse spinal instability model can be constructed by biting off the spinous process and stripping the paraspinal muscles. Cartilage tissue proliferation, fibrous ring rupture, nucleus pulposus shrinkage, intervertebral disc herniation, and osteophyte formation can be observed 6-12 months after surgery.

　　2. A structural induced intervertebral disc herniation animal model was established by injecting a 30kDa N-terminal fibronectin fragment into the intervertebral disc of rabbits. Rabbits treated with chemical drug injury showed progressive abnormalities in the nucleus pulposus structure, and intervertebral disc herniation occurred at 16 weeks.

　　After surgery caused marginal damage to the anterior ring of the goat annulus fibrosus, changes in the intervertebral disc were observed. Upon incision of the annulus fibrosus, it was found that only granulation tissue was formed in the outer one-third. Within 4-6 weeks after surgery, almost all cases of rupture of the inner annulus fibrosus and protrusion of nucleus pulposus like material towards the incision site occurred.

　　Coarse needle multi-point puncture or fine needle single point puncture method: The use of puncture methods on the anterior outer side of the fibrous ring of the intervertebral disc in dogs, goats, or macaques can cause intervertebral disc degeneration in animals, while the coarse needle multi-point puncture method can produce more obvious signs of intervertebral disc herniation in a shorter period of time.

　　Endplate injury method: An intervertebral disc degeneration model is created by drilling an oblique hole through the vertebral body directly to the cartilage endplate and nucleus pulposus of rabbits. Acute endplate injury causes a decrease in nucleus pulposus pressure and redistribution of stress, leading to intervertebral disc degeneration.

　　The mechanism of intervertebral disc herniation in stress type animal models is the degenerative change of intervertebral discs caused by long-term abnormal weight-bearing, which is similar to the mechanism of human intervertebral disc herniation. The modeling mechanism of intervertebral disc fusion also relies on biomechanical factors, directly damaging the structure of intervertebral discs through abnormal mechanical stimulation. Spinal instability leads to intervertebral disc herniation models, which are achieved indirectly by surgical destruction of supporting tissues such as joint surfaces or spinous processes, repeated stimulation of spinal muscles, or fusion of adjacent segments of the spine. Structural animal models can directly damage the normal structure of intervertebral discs due to the construction method, so significant pathological and physiological changes of intervertebral discs can occur in a relatively short period of time.

　　Stress based animal models typically have advantages such as minimal experimental damage, good reproducibility, and easy control of production conditions. However, there are also shortcomings such as relatively long animal feeding times, extended experimental cycles, and limitations to small animals.

　　In the construction method of structural animal models, the injection of fibronectin fragments into the intervertebral disc causes degenerative changes by destroying structures such as the nucleus pulposus with chemical reagents. This method has low cost, strong operability, easy control of injection drug dosage, good repeatability, and relatively short experimental period. The fiber ring cutting method can be applied to large animals without damaging spinal stability, and its operability, repeatability, and reliability are better than other methods. But the surgical trauma is significant and requires high standards from the operator. The puncture method is relatively simple to operate, but it is difficult to maintain consistent puncture depth, and the mechanism of intervertebral disc herniation is significantly different from that of human diseases. The terminal plate injury method progresses rapidly, but due to the significant damage, it affects the survival rate of experimental animals and is currently less commonly used.