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目的探讨miRNAs参与颞叶癫痫(TLE)的发生发展,TPM治疗颞叶癫痫中有miR-153的参与及其与凋亡之间的联系。方法利用锂-匹罗卡品诱发癫痫,随机将80只大鼠分为四组:正常对照组,TLE组,TPM低剂量组(40mg/kg)和TPM高剂量组(80 mg/kg)。通过microRNA芯片分析测定上述四组大鼠海马中miRNAs表达谱的改变,HE染色观察各组大鼠海马组织与细胞的形态学改变,并利用免疫蛋白印迹、免疫组化方法测定上述各组海马中caspase-3蛋白的表达水平。结果与对照组相比,TLE大鼠海马中检测到了6个上调的miRNAs(miR-204,-214,-210,-466c,-298,-207)和12个下调的miRNAs(miR-153,-34a,-362,-377,-101a,-382,-598,-488,-383,-376b-3p,-380,-9)。经TPM治疗后,上调的6个miRNAs发生了下调,12个下调的miRNAs则出现了上调,其中miR-153在上调的miRNAs中变化最为显著。此外,在TLE大鼠海马中能够检测到caspase-3的表达水平明显增加,经TPM治疗后其表达水平下降,且TPM高剂量组中大鼠海马caspase-3的表达较TPM低剂量组更低。结论 MiRNAs参与到了TLE的发生发展中,且miR-153有望成为TLE治疗中的重要靶点。MiR-153参与到了癫痫的发生,TPM治疗能够使miR-153发生上调。TPM能够减少大鼠海马中凋亡的发生。
Objective To investigate the involvement of miRNAs in the development of temporal lobe epilepsy (TLE), the involvement of miR-153 in temporal lobe epilepsy and its association with apoptosis. Methods 80 epilepsy rats were randomly divided into four groups: normal control group, TLE group, TPM low dose group (40mg / kg) and TPM high dose group (80 mg / kg). The changes of miRNAs expression in the hippocampus of the four groups were determined by microRNA chip analysis. The morphological changes of hippocampal tissues and cells in each group were observed by HE staining. Immunohistochemistry and Western blotting were used to detect the expression of miRNAs in the hippocampus Caspase-3 protein expression levels. Results Compared with the control group, six upregulated miRNAs (miR-204, -214, -210, -466c, -298, -207) and 12 downregulated miRNAs (miR-153, -34a, -362, -377, -101a, -382, -598, -488, -383, -376b-3p, -380, -9). After TPM treatment, the up-regulated 6 miRNAs were down-regulated, and 12 down-regulated miRNAs were up-regulated, of which miR-153 was most significantly changed in up-regulated miRNAs. In addition, the expression of caspase-3 was significantly increased in the hippocampus of TLE rats. The expression level of caspase-3 was decreased after treatment with TPM, and the expression of caspase-3 in hippocampus of TPM high-dose group was lower than that of TPM low-dose group . Conclusions MiRNAs are involved in the development of TLE, and miR-153 is expected to be an important target in TLE therapy. MiR-153 is involved in the development of epilepsy. TPM treatment can up-regulate miR-153. TPM can reduce the incidence of apoptosis in the hippocampus of rats.