GdCl3对小鼠肝脏再生早期Cyp7A1基因转录影响.docVIP

GdCl3对小鼠肝脏再生早期Cyp7A1基因转录影响 　 作者：黄雄飞，陈良万，黄文栋 【摘要】 　　目的： 探讨小鼠肝脏再生早期氯化钆(GdCl3)通过作用于枯否细胞影响胆酸介导的Cyp7A1基因转录的抑制. 方法： 运用GdCl3 (10 mg/kg, iv.) 或PBS (0.2 mL, iv.) 处理C57BL/6小鼠24 h后，切除小鼠70%的肝脏，于术后第1日处死小鼠，收集肝脏，采用实时定量RTPCR方法检测肝脏中Cyp7A1, TNFα和IL6基因的表达. 结果： 肝脏再生的第1日, 与PBS对照组相比, GdCl3处理组中Cyp7A1 mRNA 的表达降低(Plt;0.01), 而细胞因子TNFα和IL6 mRNA 的表达升高 (Plt;0.01). 结论： 在肝脏再生的早期, GdCl3可增进胆酸介导Cyp7A1基因转录的抑制, 这种作用是通过促使枯否细胞产生细胞因子TNFα 和IL6来实现. 【关键词】 GdCl3；枯否细胞；细胞因子类；Cyp7A1基因；肝再生 　　Effect of gadolinium chloride on Cyp7A1 gene transcription during early stages of mouse liver regeneration 【Abstract】 AIM: To observe the effect of gadolinium chloride (GdCl3 ) on Kupffer cells regarding the bile acidmediated suppression of Cyp7A1 gene transcription during early stages of the mouse liver regeneration. METHODS: Twenty four hours before 70% hepatectomy, C57BL/6 mice were treated with either GdCl3 (10 mg/kg, iv) or PBS (0.2 mL, iv). Mice were sacrificed at the first day after surgery. Livers were harvested and Cyp7A1, TNFα , IL6 gene expressions were measured by realtime RTPCR. RESULTS: During the first day of liver regeneration, compared to the PBS pretreated mice, the Cyp7A1 gene expression was dramatically decreased (Plt;0.01). In contrast, the TNFα and IL6 gene expressions were significantly increased in GdCl3 pretreated mice (Plt;0.01). CONCLUSION: During the early stages of liver regeneration, the enhanced effect of the bile acidmediated suppression of Cyp7A1 gene transcription by GdCl3 is via its stimulation of cytokine production from Kupffer cells. 【Keywords】 GdCl3; Kupffer cells; cytokines; Cyp7A1 gene; liver regeneration 　　0引言 胆固醇在肝脏内代谢为胆酸是胆固醇从体内清除的重要方式. Cyp7A1基因编码胆固醇转化成胆酸过程中的限速酶胆固醇7α羟化酶. 胆酸可通过多种机制来反馈抑制Cyp7A1基因的表达［1］. Miyake 等［2］研究发现当胆酸在肝脏内达到一定浓度时，会诱导枯否细胞合成并释放细胞因子. 这些细胞因子作用于肝细胞后，可导致Cyp7A1基因表达的抑制. 通过调控Cyp7A1基因的表达来保持胆酸代谢的平衡是小鼠肝脏部分切除术 (partial hepatectomy, PH) 后正常再生的重要条件. 氯化钆(gadolinium chloride, GdCl3) 是一种稀有的地球金属，它可以破坏肝脏枯否细胞的功能，因此常被用来研究与枯否细胞相关的疾病或毒性过程的发生机制. GdCl3的作用效应目前还有争议. 本研究探讨在小鼠70%