重组人促红细胞生成素对癫痫大鼠海马齿状回的影响

Effect of recombinant human erythropoietin on dentate gyrus in epileptic rats

目的探讨重组人促红细胞生成素(recombinant human erythropietin,r-HuEPO)对癫痫大鼠海马齿状回的影响。方法 140只大鼠按随机数字表法分为正常对照组20只,余120只制作氯化锂-匹罗卡品颞叶癫痫模型,符合条件者采用随机数字表将其分为癫痫治疗组和癫痫组;各组均经腹腔注射BrdU,治疗组同时予以r-HuEPO处理;以FJ-B(Fluoro-Jade B)免疫荧光观察神经元变性情况,BrdU免疫组化观察细胞增殖情况,Timm’s染色观察齿状回苔藓纤维发芽情况。结果海马齿状回神经元变性在癫痫组(32.32±5.09)较治疗组(11.12±0.75)和对照组(6.50±1.08)明显(P<0.01),而治疗组和对照组相比无显著差异;第9天细胞增殖在癫痫组(92.8±2.97)较治疗组(16.95±0.54)和对照组(12.80±2.13)明显(P<0.01),治疗组和对照组相比无显著差异;第28天细胞增殖在癫痫组(146.45±5.91)较治疗组(46.27±2.93)和对照组(38.52±3.10)明显(P<0.01),治疗组和对照组相比无显著差异;Timm’s染色结果表明在第14天,癫痫组(0.45±0.19)苔藓纤维发芽比对照组(0.10±0.11)明显(P<0.05),第28天癫痫组(3.60±0.16)比治疗组(0.55±0.10)和对照组(0.30±0.11)更加明显(P<0.01),治疗组与对照组比差异不明显(P>0.05)。结论癫痫能诱发大鼠海马齿状回神经元变性、细胞增殖和苔藓纤维发芽;r-HuEPO处理能降癫痫大鼠海马齿状回神经元变性和细胞增殖,并能抑制苔藓纤维发芽。

Objective To investigate the effect of recombinant human erythropietin（r-HuEPO） on dentate gyrus of rats with status epilepticus.Methods A total of 140 SD adult male rats were randomly divided into a control group including 20 rats and a model group including 120 rats,which were intraperitoneally injected with lithium chloride-pilocarpine to establish rat model of temporal lobe epilepsy.Then the survival rats were randomly and equally subdivided into an r-HuEPO＋SE group and a SE group.All rats were injected with BrdU intraperitoneally for 6 d,and rats of the r-HuEPO＋SE group were additionally injected with r-HuEPO.Rats＇ neuronal degeneration was observed by Fluoro-Jade B（FJ-B） immunofluorescence on the 4th day,cell proliferation was observed by BrdU immunohistochemistry on the 9th and 28th days,and mossy fiber sprouting was observed by Timm＇s staining on the 14th and 28th days.Results Neuronal degeneration in dentate gyrus in the SE group（32.32±5.09） was more serious than that in the r-HuEPO＋SE group（11.12±0.75） and control group（6.50±1.08）（P0.01）,but the difference between the r-HuEPO＋SE group and the control group was not statistically significant（P0.05）.Cell proliferation on the 9th and 28th days in the SE group [（92.8±2.97） and（146.45±5.91）] was more obvious than that in the r-HuEPO＋SE group [（16.95±0.54） and（46.27±2.93）] and the control group [（12.80±2.13） and（38.52±3.10）（P0.01）],but the difference between the r-HuEPO＋SE group and the control group was not statistically significant（P0.05）.Mossy fiber sprouting on the 14th day in the SE group（0.45±0.19） was more obvious than that in the control group（0.10±0.11）（P0.05）.On the 28th day,mossy fiber sprouting in the SE group（3.60±0.16） was more obvious than that of the r-HuEPO＋SE group（0.55±0.10） and control group（0.30±0.11）（P0.01）,but the difference between the control group and the r-HuEPO＋SE group was not significant（P0.05）.Conclusion r-HuEPO can reduce neuronal degeneration,cell proliferation and mossy fiber sprouting in dentate gyrus of epileptic rats.