| Objective:1. Through the observation in rats model of posttraumatic epilepsy hippocampus and damage cortex around the lesions that the dynamic expressions of p-m TOR(Ser2448)、p-P70S6K(Thr389),understanding of rats after PTE that the m TOR pathway activation condition and the process of dynamic change.2. To intervene these above with rapamycin. And comparied the the expression of p-m TOR(Ser2448) 、 p-P70S6K(Thr389) to explore possible prevention and cure mechanisms of PTE.Methods:1. 74 healthy adult male Sprague-Dawley rats were divided into the normal control group(A),the saline control group(B)and the epilepsy model group(C) using random number table. The treatment group respectively.Through without treatment group,intracortical injection of physiological saline or ferrous chloride(0.1mol/L, 10 u L) respectively made PTE models.Behavior was observed.Hematoxylin-eosin(HE) staining and the expression of p-m TOR(Ser2448) 、p-P70S6K(Thr389) in the hippocampal dentate gyrus and damage cortex around the lesions were detected immunohistochemically with the professional image analysis software to observe the pathological changes.2. 69 healthy adult male Sprague-Dawley rats were divided into the control group(D)and the treatment group(E)using random number table.Intraperitoneal injection of rapamycin( 6mg/kg/d) was enforced to PTE models of the treatment group.Intraperitoneal injection of same volume vehicle solution containing 5%Tween 80, 5% PEG 400, and 4% ethanol was enforced to PTE models of the control group.Behavior was observed, brains were removed at different time points.Hematoxylin-eosin(HE) staining and the expression of p-m TOR(Ser2448) 、p-P70S6K(Thr389) in the hippocampal dentate gyrus and damage cortex around the lesions were detected immunohistochemically to observe the pathological changes.Results:1. 105 PTE models had been made successfully, the success rate of modeling is 88.24%. C group of rats in seizure frequency gradually increased, 1w cumulative number of seizures increased significantly. After 1w attack cumulative number of attacks decreased gradually. The number of seizures in D group than E group significantly reduced the number of seizures(P<0.05).2. A group, dentate gyrus and frontal lobe cells with clear hierarchy no neuron degeneration and necrosis change.Fe Cl2 compared with B group that hippocampal dentate gyrus and damage cortex around the frontal lobe the pathologic change seriously, granular cell necrosis\ hyperplasia, neuronal necrosis\ hyperplasia and glial cell proliferation obviously. The expression of p-m TOR(Ser2448) 、p-P70S6K(Thr389) little in the dentate gyrus of hippocampus of A group.The expression of p-m TOR(Ser2448) in C group and B group increased significantly 1week later,and decreased after 2 weeks,but increased after 4 weeks,the difference has statistical significance between groups of the same time(P<0.05). The expression of p-P70S6K(Thr389) in C group increased significantly 1 week later,and decreased after 2 weeks,but increased after 4 weeks, C and B group the difference has statistical significance between groups of the 1hour 、 24 hour 、1weeks 、 4weeks(P<0.05).The expression of p-m TOR(Ser2448) 、p-P70S6K(Thr389) little in the frontal lobe of A group.The expression of p-m TOR(Ser2448) in C group and B group increased significantly 1 week later,and decreased after 2 weeks,but increased after 4 weeks,the difference has statistical significance between groups of the same time(P<0.05).The expression ofp-P70S6K(Thr389) little in the frontal the difference has statistical significance between groups of the same time(P<0.05).3. Compared to D group,the hippocampal dentate gyrus and damage cortex around the frontal lobe of E group the pathological damage reduce. Compared to vehicle treatment group, the expression of p-m TOR(Ser2448) of treatment group were weaker at each time piont.(P<0.05).Compared to control group, the expression of p-P70S6K(Thr389) of D group were weaker at each time piont. E group and D group the difference has statistical significance between groups of the 1hour 、24hour 、 1weeks 、 4weeks(P<0.05),but there was no statistically significant difference between 2 weeks(P>0.05).Conclusions:1. After intracortical injection of Fe Cl2, through some mechanism induced hippocampal dentate gyrus and damage cortex around the frontal lobe the neuron and glial cells expressing enhanced p-m TOR(Ser2448) and p-P70S6K(Thr389).The hippocampal dentate gyrus, damage cortex around the frontal lobe the neuron and glial cells etal abnormal proliferation, may play an important role in the epileptogenesis of PTE.2. Some reactions after PTE could lead hippocampal dentate gyrus and cortex structure disorder. The m TOR inhibitor rapamycin can reduce the number of seizures in rats PTE model Rapamycin can repress the abnormal expression of the p-m TOR(Ser2448) and p-P70S6K(Thr389) in hippocampal dentate gyrus and damage cortex around the frontal lobe.Can effectively alleviate the patho-reconstitution process, playing an important role in the prevention and cure in late PTE. |
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