动物造模,药效评价,癫痫 z-bio 2024-09-24 433

　　1. Modeling material animals: Wistar rats, male or female, weighing 200-300g; Drug: kain-ic acid (KA).

　　2. Modeling method: Healthy male Wistar rats were injected intraperitoneally with physiological saline at doses of 6mg/kg, 10mg/kg, and 14mg/kg, respectively, to establish a good epilepsy model. Generally, 10mg/kg KA intraperitoneal injection has better modeling effect.

　　In addition, local administration can also be used, including intraventricular administration (dose of 0.4-1.5 μ g) and local injection into the brain (dose of 0.5-2 μ g); Alternatively, systemic administration of 8-12mg/kg KA can be administered subcutaneously or intravenously.

　　3. Modeling principle: Hyaluronic acid is a structural analogue of glutamate, an excitatory amino acid neurotransmitter in the brain. In the brain, it acts on the presynaptic membrane KA receptors of glutamate or aspartic acid terminals, stimulating the release of endogenous excitatory amino acids and inhibiting their reuptake. Administering a convulsive dose of KA to the brain or system can induce experimental epileptic seizures in animals.

　　4. Changes after modeling: 10-20 minutes after injection, the rats gradually shifted from a state of free movement to a quiet or prone position, followed by dull eyes and slight tremors in the head and facial muscles. Then it enters a period of small seizures, accompanied by blinking, ear tremors, and scratching movements. Then it gradually enters a major attack, with mild cases showing the front limbs extended, the head tilted to one side, and the whole body constantly shaking. Severe cases may manifest as strong muscle twitching, screaming, drooling at the corners of the mouth, stiff limbs, or sudden jumping, standing upright, rolling, and falling, lasting for about 5 minutes.

　　The morphological changes in the hippocampus of epileptic rats are mainly manifested by a significant reduction in pyramidal cells in the CA3 region and interneurons in the dentate gyrus, as well as varying degrees of damage to pyramidal cells in the CA1 region. The pyramidal cells and granulosa cells in the CA2 region remain intact. In addition, abnormal mossy fiber sprouting and glial cell proliferation were observed in the dentate gyrus of rats.