The investigation of regulatory mechanism on liver regeneration after massive hepatectomy

背景)肝切除术后肝功能衰竭是最重要的术后并发症之一。此外，在肝移植后发生肝功能衰竭，小尺寸移植物是一个重要因素。本研究旨在阐明大规模肝切除术后的调控机制和术后肝衰竭的控制方法。方法与结果)对肝脏缺血再灌注损伤（I/R损伤）的调节作用(1)卵泡抑素大鼠模型，未观察到转氨酶水平和存活率的改善。(2)氟伐他汀术前治疗（口服）氟伐他汀可降低I/R损伤后转氨酶水平。此外，我们通过实时PCR方法证实了I/R损伤后eNOS、几种细胞因子和NOX4的表达。我们利用DNA芯片分析了肝癌切除术后的基因表达，证实STAT3和HO-1的基因表达在手术后增强。FK506对大块肝切除术后肝脏再生的调节作用(1)FK506在大块肝切除术（90%）模型中，FK506在术后72hr促进肝脏再生。大鼠肝大部切除（90%）模型血清FK506水平高于70%肝大部切除模型。(2)日本中草药：术前治疗（口服）有加速胆道排泄的作用，可提高术后生存率，降低转氨酶水平。此外，In-Chin-co-to还能加速大面积肝切除术后的肝脏再生。免疫组化染色显示PCNA和HO-1表达显著升高，SMA表达显著降低。(3)氟伐他汀术前治疗（口服）氟伐他汀对血管性他汀等I/R损伤有保护作用，可促进肝再生，降低肝切除术后总胆红素水平。摘要)本研究采用分子生物学方法，阐明了肝再生的调控机制，以及几种肝再生调节剂在大块肝切除术中的作用。然而，我们无法阐明激活素对肝脏再生的调节作用，因为我们在纯化激活素方面有困难。少

Background)Liver failure after massive hepatectomy is one of the most important postoperative complication. Furthermore, in outbreak of liver failure after liver tranplantation, small-for-size graft is an important factor. In this study, we conducted to clarify the regulatory mechanism after massive hepatecomy and the control method for postoperative liver failure.Method and Results)1. Regulation of ischemic reperfusion injury (I/R injury) of the liver(1) follistatinIn rat model, improvement of transaminase levels and survival rate were not observed.(2)fluvastatinPreoperative treatment (oral administration) of fluvastatin decreased transaminase levels after I/R injury. Furthermore, we confirmed expression of eNOS, several cytokines and NOX4 on realtime PCR method after I/R injury.2. Gene expression after massive hepatectomy (90%)We analyzed gene expression after massive hepatectomy using the DNA microarray, and confirmed that Gene expression of STAT3 and HO-1 was enhanced after operati … More on.3. Effect of modulation on liver regeneration after massive hepatectomy(1)FK506In massive hepaatectomy (90%) model, FK506 accelerated liver regeneration in 72hr after operation. Furthermore, serum level of FK506 in massive hepatectomy (90%) model was higher than that in 70% hepatectomy model.(2)In-Chin-co-to (Japanese herbal medicine)Preoperative treatment (oral administration) of In-Chin-co-to which have effect of acceleration for biliary excretion improved postoperative survival and decreased transaminase levels. Furthermore, In-Chin-co-to accelerated liver regeneration after massive hepatectomy. In immunohisitochemical staining, expression of PCNA and HO-1 was significantly higher and a SMA was significantly lower.(3) fluvastatinPreoperative treatment (oral administration) of fluvastatin which have protection effect for I/R injury such as vascular statin accelerated liver regeneration and decreased total-billilubin level afar massive hepatectomy. In immunohisitochemical staining, expression of a SMA was suppressedSummary)In this study, we clarified the regulatory mechanism of liver regeneration and effect of several modulators for liver regeneration on massive hepatectomy using molecular biological method. However, we were not able to elucidate the regulation of liver regeneration using activin, because we had difficulty with the purification of activin. Less