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GADD45α对大鼠部分肝切除后肝脏再生的调控作用
Regulatory role of GADD45α in rat liver regeneration
目的 探讨生长阻滞和DNA损伤诱导基因GADD45α在大鼠部分肝切除（PH）后肝再生中的作用及其调节机制。方法 将114只大鼠随机分为19组，2/3肝切除9组，手术对照9组，正常对照1组，制作大鼠部分肝切除模型，然后用大鼠基因组芯片Rat Genome 230 2.0检测部分肝切除后再生肝的基因表达变化，采用实时定量PCR技术验证芯片检测结果。利用谱函数（Ep）分析基因表达变化预示的生理活动改变，进而通过Ingenuity Pathway Analysis（IPA）汇总GADD45α调控肝再生的信号通路并分析其可能的分子机制。 结果 GADD45α在PH后2~6h、24h和36~72h均表达上调，GADD45α通过NF-κB、p38PRAK、p53、STAT3-p21、STAT3-Bcl-2、STAT3-cMyc等6条途径参与大鼠部分肝切除后的肝脏再生调控。谱函数分析发现，GADD45α调控的生理活动的变化情况基本与大鼠肝再生进程相符。
结论 GADD45α在大鼠肝再生中可能通过上述信号通路调控细胞增殖、细胞周期和细胞存活等生理活动，进而调节肝脏的再生。
Objective To explore the role and mechanism of growth arrest and DNA damage inducible gene GADD45α during liver regeneration (LR) after partial hepatectomy (PH) in rats. Methods 114 rats were randomly divided into 19 groups, 9 groups of 2/3 liver resection, 9 control groups and 1 normal control group. The rat PH model was established, rat Genome 230 2.0 array was used to detect the gene expression profiles of the regenerated liver after PH, and Real-time PCR technique was used to verify the reliability of the microarray. Expression profile function (Ep) was used to analyze the biological processes that regulated by GADD45α, and then Ingenuity Pathway Analysis (IPA) was used to summarize the signal pathway of GADD45α regulating LR and analyze its possible mechanism. Results The microarray results showed that Gadd45α was up-regulated at 2-6 hours, 24 hours and 36-72 hours after PH. The IPA results indicated that GADD45α regulated various physiological activities which were involved in rat LR via NF-κB, p38PRAK, p53, STAT3-p21, STAT3-Bcl-2 and STAT3-cMyc paths. The results revealed that changes of physiological activity were in line with the basic process of rat LR. Conclusion GADD45α may regulate cell proliferation, cell cycle and cell survival and other physiological activities during the regeneration of liver in rat through the above pathways.
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