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[Effects of cyclin dependent protein kinase inhibitor olomoucine on the neuronal apoptosis after status epilepticus: experiment with rats].
- Source :
-
Zhonghua yi xue za zhi [Zhonghua Yi Xue Za Zhi] 2007 Aug 07; Vol. 87 (29), pp. 2025-9. - Publication Year :
- 2007
-
Abstract
- Objective: To investigate the effects of olomoucine, a cyclin dependent protein kinase (CDK) inhibitor, on the neuronal apoptosis after status epilepticus (SE).<br />Methods: Lithium chloride was injected intraperitoneally, and pilocarpine was injected intraperitoneally after 18 h to 24 SD rats so as to cause SE. Twenty-two of the 24 rats developed SE and 2 of them died. The surviving 20 rats were then randomly divided into 2 equal groups: olomoucine group, injected intracerebroventricularly after the SE was terminated by diazepam and chloral hydrate once a day for 3 days, and SE group, infused intracerebroventricularly with DMSO solution Another 10 rats were injected intraperitoneally with normal saline and then infused intracerebroventricularly with DMSO solution to be used as control group. Six hours after SE attack 5 rats from each group were killed respectively with their brains taken out. Semiquantitative RT-PCR was used to detect the mRNA expression of anti-inflammatory cytokines, such as interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. Three days later the other 5 rats in each group were killed with their entorhinal cortex and hippocampus taken out. TUNEL was used to observe the apoptosis. Immunofluorescence (IF) staining was used to detect the expression of neuronal nuclear nucleoprotein (NeuN) and cyclin B1.<br />Results: TUNEL showed that apoptotic neurons were rare in the control group and were numerous in the SE group, especially in the entorhinal cortex and the hylus of dentate gyrus, and the number of apoptotic neurons in the hylus of dentate gyrus of the olomoucine group was not significantly different from that of the control group (P < 0.05), however, the number of apoptotic cells in the entorhinal cortex of the olomoucine group was still significantly higher than that of the control group (P < 0.05). IF staining demonstrated that in the control group the co-expression of NeuN and TUNEL-labeled cells was weak; and in the SE group the co-expression of NeuN and TUNEL was significantly increased compared with that in the control group (P < 0. 05). The number of cyclin B1 positive cells in the olomoucine group was 18.22 +/- 3.99, significantly lower than that of the SE group (24.57 +/- 6.78, P < 0.05). Semiquantitative RT-PCR showed that the IL-1beta and TNF-alpha mRNA expression levels of the SE group were both significantly higher than those of the control group (both P < 0.05), and the IL-1beta and TNF-alpha mRNA expression levels of the olomoucine group, except the TNF-alpha mRNA expression in the cortex, were all significantly lower than those of the SE group (all P < 0.05), and not significantly different from those of the control group (all P > 0.05).<br />Conclusion: Olomoucine treatment can inhibits cell cycle protein B1 expression, anti-inflammatory cytokines such as IL-1beta and TNF-alpha secretion, thus decreasing neuronal death and providing neuroprotection after SE, which suggests a potential promising therapeutic way for epilepsy treatment.
- Subjects :
- Animals
Brain drug effects
Brain metabolism
Brain pathology
Cyclin B metabolism
Cyclin B1
Enzyme Inhibitors pharmacology
Fluorescent Antibody Technique
In Situ Nick-End Labeling
Interleukin-1beta genetics
Lithium Chloride
Male
Nerve Tissue Proteins metabolism
Neurons cytology
Neurons metabolism
Nuclear Proteins metabolism
Phosphopyruvate Hydratase metabolism
Pilocarpine
RNA, Messenger genetics
RNA, Messenger metabolism
Random Allocation
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Status Epilepticus chemically induced
Tumor Necrosis Factor-alpha genetics
Tumor Necrosis Factor-alpha metabolism
Apoptosis drug effects
Cyclin-Dependent Kinases antagonists & inhibitors
Kinetin pharmacology
Neurons drug effects
Status Epilepticus physiopathology
Subjects
Details
- Language :
- Chinese
- ISSN :
- 0376-2491
- Volume :
- 87
- Issue :
- 29
- Database :
- MEDLINE
- Journal :
- Zhonghua yi xue za zhi
- Publication Type :
- Academic Journal
- Accession number :
- 17925171