AIM:To address to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue loss. METHODS:The ability of the liver to regenerate is remarkable on both clinical and biological grounds. Basic mechanisms underlying this process have been intensively investigated. However, it is still debated to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue loss. We addressed this issue using a genetically tagged system. We were able to follow the fate of single transplanted hepatocytes during the regenerative response elicited by 2/3 partial surgical hepatectomy (PH) in rats. Clusters of transplanted cells were 3D reconstructed and their size distribution was evaluated over time after PH. RESULTS:Liver size and liver DNA content were largely recovered 10 d post-PH, as expected (e.g., total DNA/liver/100 g b.w. was 6.37 ± 0.21 before PH and returned to 6.10 ± 0.36 10 d after PH). Data indicated that about 2/3 of the original residual hepatocytes entered S-phase in response to PH. Analysis of cluster size distribution at 24, 48, 96 h and 10 d after PH revealed that about half of the remnant hepatocytes completed at least 2 cell cycles. Average size of hepatocytes increased at 24 h (248.50 μm2 ± 7.82 μm2, P = 0.0015), but returned to control values throughout the regenerative process (up to 10 d post-PH, 197.9 μm2 ± 6.44 μm2, P = 0.11). A sizeable fraction of the remnant hepatocyte population does not participate actively in tissue mass restoration. CONCLUSION:Hyperplasia stands as the major mechanism contributing to liver mass restoration after PH, with hypertrophy playing a transient role in the process.

译文

目的:探讨肥大和增生在主要组织丢失后在多大程度上有助于肝脏肿块的恢复。
方法:无论从临床还是生物学的角度来看,肝脏的再生能力都很显着。深入研究了此过程的基本机制。然而,仍存在争议,在主要组织丢失后,肥大和增生在多大程度上有助于肝块的恢复。我们使用基因标记的系统解决了这个问题。在2/3部分外科手术肝切除术(PH)引起的再生反应过程中,我们能够追踪单个移植肝细胞的命运。 PH移植后,将移植的细胞簇进行3D重建,并评估其大小分布。
结果:在PH后10 d,肝脏大小和肝脏DNA含量在很大程度上恢复了(如在PH前的总DNA /肝脏/ 100 g b.w.为6.37±0.21,而在PH后10 d恢复至6.10±0.36)。数据表明,约有2/3的原始残余肝细胞响应PH而进入S期。 PH后24、48、96 h和10 d的簇大小分布分析表明,大约一半的残留肝细胞完成了至少2个细胞周期。肝细胞的平均大小在24 h时增加(248.50μm2±7.82μm2,P = 0.0015),但在整个再生过程中恢复到对照值(PH后长达10 d,197.9μm2±6.44μm2,P = 0.11)。相当一部分肝细胞残余不能积极参与组织块的恢复。
结论:增生是造成PH后肝脏肿块恢复的主要机制,肥大在此过程中起暂时作用。

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