| Objective：To observe the protective effects of Oxymatrine(OXY) on the hippocampalneurons of Penicillin-induced epileptic rats, the behavior and pathological changes as well as thehistorical changes of in hippocampal nerve cells.Methods：352Sprague Dawley（SD） rats were randomly divided into four groups,(1)normal saline control group (NS）(n=88),(2)epilepsy group(EP)(n=88),(3)Oxymatrainegroup(OXY)(n=88),(4) the sodium phenobarbital group (PBS)(n=88). The epileptic seizureswere induced by intraperitoneal injection of penicillin. Brain sections of the hippocampal CA1region were compared both by optical microscope (H.E. staining) and by electron microscope.The JNK signal pathway was also observed by compareing the p-JNK immuno-positive cells inthe hippocampal CA1area. The spatial learning and memory ability was tested by the MorrisWater Maze experiment.Results：①All of EP group have achieved Ⅳ or above grade standard of seisures, andthe latency of EP group is9.2±4.6min, and four deaths, the mortality rate was40%(4/10); There is only one rat in OXY group appeared Ⅳ or Ⅴgrade seisures on24.5min, and subsequently died, the mortality rate was10%(1/10); PBS group hadno seizures and no death.②Pathological changes of neuronsNeurons in EP group were most seriously damaged, with obvious degenerationand necrosis, especially at3.0h and6.0h after epilepsy induced. The damage ofneurons in PBS group was lighter than EP group. Neurons in OXY group hasscattered and mild damages. Hippocampal neurons were round and oval in shape, with normal membrane structure, and uniform cytoplasm under light microscopy.The nuclear membrane and nucleolus were clearly visible.Observe the ultrastructure of hippocampal neurons by electron microscopyThe structures of capillaries, neurons, organelles and synapses were normal inNS group. The nuclei appeared pyknosis and mitochondrial was damaged in EPgroup at the point of0.5h after PN injection, capillary congestion and markeddamages of mitochondria were obvious at1.5h; and the damage of membrane,nuclear, were even more severe at3.0h and6.0h points. The neuron injury wasreduced at12h. The damage of OXY group was lower than the EP group and PBSgroup at different time points but mild pyknosis was also seen.③Testing spatial learning and memory by Morris Water Maze: The escapelatency of OXY group obviously improved, and the times and length of the path inthe target area is the same. In spacial probe test, the average number of crossplatform of NS group was12.8times, EP group was5.8times, OXY group was11.2times and PBS group was7.6times. The OXY group was significantly increased.There were five rats of six which using the efficient spatial search strategy in NSgroup, in EP group there iwas only one rat, in OXY group was four, and in PBSgroup was also only one, the difference was statistically significant (P <0.05).④Counting p-JNK immunoreactive cell: The number of positive cells in EPgroup is significantly increased on0.5h and1.5h after epilepsy induced, and thenumber was risen to the highest value on3.0h, it is back down at6.0h and close tothe NS Group at12.0h. The number of OXY group were less than the EP group andPBS group on different time points (P <0.05).Conclusions①OXY has a strong antiepileptic effect for prolonging the seizure latency andreducing the degree of seizures in rats,. ②OXY could reduce the hippocampal neurons pathology and ultrastructuraldamages in PN-induced epileptic rats, improve its spatial learning and memoryfunction, and inhibit the JNK signal transduction pathway activation in hippocampalneurons. |
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