静脉导管未闭的血流量与早期新生儿肝功能呈显著相关性

Background: The biochemical features of portosystemic venous shunt with high flow volume are hypergalactosaemia, hyperammonaemia, prolonged blood coagulation time, and raised serum bile acid concentration. The ductus venosus remains open with shunt flow in most neonates for a certain period after birth. However, the effects of blood flow through the ductus venosus on neonatal liver function remain unclear. Objective: To elucidate the effect of patency of the ductus venosus on liver function in early neonates. Methods: Subjects were divided into three groups by gestational age (group I, 29- 32 weeks; group II, 33- 36 weeks; group III, 37- 41 weeks). The shunt flow volume through the ductus venosus was examined serially using ultrasonography, and correlations between flow volume and liver function in the respective groups were calculated during the first week after birth. Results: Group I had a higher flow volume and later functional closure than the other two groups. Plasma ammonia and serum total bile acid concentrations correlated with flow volume in groups I and II, and blood galactose and galactose 1 - phosphate concentrations correlated significantly with flow volume in group III. Percentage hepaplastin also correlated significantly with flow volume in all groups, but plasma vitamin K concentration did not in any group. Conclusions: Patent ductus venosus has a considerable effect on crucial liver functions such as ammonia detoxification, blood coagulation, and regulation of serum total bile acid concentration in early neonates.

Extent of liver resection modulates the activation of transcription factors and the production of cytokines involved in liver regeneration

AIM： To investigate the molecular events involved in liver regeneration following subtotal hepatectomy （SH） as previous studies have largely focused on partial hepatectomy （PH）. METHODS： Male Wistar rats were subjected to 70% PH or 90% SH, respectively, and sacrificed at different times after surgery. Untreated and sham-operated animals served as controls. Serum and liver samples were obtained to investigate liver function, apoptosis （TUNEL assay） and transcription factors （NF-KB, Stat3; ELISA） or cytokines （HGF, TNF-α, IL-6, TGF-α, TGF-β; quantitative RT-PCR） involved in liver regeneration. RESULTS： Serum levels of ALT and AST in animals with 70% PH differed significantly from sham-operated and control animals. We found that the peak concentration 12 h after surgery returned to control levels 7 d after surgery. LDH was increased only at 12 h after 70% PH compared to sham. Bilirubin showed no differences between the sham and 70% resection. After PH, early NF-kB activation was detected 12 h after surgery （313.21 ± 17.22 ng/mL）, while there was no activation after SH （125.22 ± 44.36 ng/mL） compared to controls （111.43 ± 32.68 ng/mL） at this time point. In SH, however, NF-kB activation was delayed until 24 h （475.56 ± 144.29 ng/mL）. Stat3 activation was similar in both groups. These findings correlated with suppressed and delayed induction of regenerative genes after SH （i.e. TNF-α 24 h postoperatively： 2375 ± 1220 in 70% and 88 ± 31 in 90%; IL-6 12 h postoperatively： 2547 ± 441 in 70% and 173 ± 82 in 90%）. TUNEL staining revealed elevated apoptosis rates in SH （0.44% at 24 h; 0.63% at 7 d） compared to PH （0.27% at 24 h; 0.15% at 7 d）. CONCLUSION： The molecular events involved in liver regeneration are significantly influenced by the extent of resection as SH leads to suppression and delay of liver regeneration compared to PH, which is associated with delayed activation of NF-kB and suppression of proregenerative cytokines.

Metabolism for cyclosporin A during liver regeneration after partial hepatectomy in rats

AIM： To elucidate the metabolism and the effect of the cyclosporin A （CyA） as a representative immuno- suppressive drug used in transplantation in a partially hepatectomized rat model. METHODS： CyA was administered to rats that underwent a 70% hepatectomy. These rats were randomly assigned into three groups according to the dose of CyA administration as follows; （group I） water, （group 2） 5 mg/kg CyA, （group 3） 10 mg/kg CyA. On postoperative days-1, 3, 7 and 14, the rats were killed to analyze the serum concentration of CyA, the liver regeneration ratio, biochemical or histological markers, and mRNA expression using reverse transcriptase-poly- merase chain reaction method to determine albumin and cytochrome p450 expression. RESULTS： The serum concentration of CyA in group 3 was significantly higher than group 2 during liver regeneration. CyA enhanced the liver regeneration in a dose dependent manner. The mRNA expression associated with CyA metabolism was significantly decreased on day 14, while preserving the albumin producing activity. CONCLUSION： These data indicate that the p-450 activity required to metabolize the CyA may be reduced during regeneration of the remnant liver after a hepatectomy, which may, therefore, be linked to difficulty in controlling the optimal dose of CyA during early period of LDLT.