dc.description.abstract | Liver is a core organ in our body.
Although it contains good regeneration ability,
hepatic failure can still occur after massive
hepatic injury or hepatectomy. Because of the
high incidence of hepatitis B carrier and so as
to many hepatoma patients, the mortality rate
of hepatic disease (including hepatoma cases)
is one of the tope ten causes of death in
Taiwan. Although there are much controversy
continues on the initiation, regulation,
metabolic changes, and termination of liver
regeneration after partial hepatectomy that
well initiate proliferation of the remaining
hepatocytes, several factors, such as
hormones, growth factors, nutritional
components, and pharmacological agents,
have been demonstrated to directly or
indirectly affect liver regeneration.
The regenerating liver is a system in
which the relationships between protooncogene
expression and cell replication
should be examined during a physiologic
growth response. Proto- oncogene expression
after partial hepatectomy is specific,
sequential, and highly regulated. As measured
by levels of mRNAs, the changes have been
detected in the expression of c-fos, c-myc,
p53, and the ras gene family (c-Ha-ras,
c-Ki-ras, and N-ras). In contrast, expression
of c-src and c-abl does not change after
partial hepatectomy while c-mos transcripts
cannot be detected in normal or regenerating
liver. In recent study, the critical roles of
some proto-oncogenes were noted in the
control of cell proliferation, differentiation,
and apoptosis by the new technique of
complementary DNA microarray. However,
mass survey and more detailed analysis by
microarry method, that will be very important,
are still nor reported.
The main purpose of this project is to
find out the variation of more than 300
regulating genes during liver regeneration
after partial hepatectomy. Male Wistar rats
around 200g were used as subject. Partial
hepatectomy (around 70%) were performed
and they will be sacrificed at 2, 4, 6, 8, 10, 12,
24, 48, 72 hours and 5, 7, 10 days after
hepatectomy. We measured: (1) weight of
remnant liver; (2) mitotic index; and (3)
genomic survey of the expression for more
than 300 proto-oncogenes by cDNA
microarray on nylon membrane, labeling of
liver mRNA hybridization and image analysis.
We found that: (1) the remnant liver weight
increased to 90% in 72h after partial
hepatectomy; (2) the mitosis of hepatocytes
increased markedly at 48h then decreased at
72h after partial hepatectomy; (3) analyzing
the gene expression of microarray chips, the
variations could be classified into 72 different
patterns including the pattern with a single
peak at 2, 4, 6, 12, 48, 72h and 5, 7 days time
sequence after partial hepatectomy. The
variation patterns also included double peaks,
enhancing trend, diminished trend, protruding
curve, excavated curve and other mixed types.
Each category of gene expression pattern
contained 40 to 218 proto-oncogenes. The
quantitative gene expression profiles should
have important implications for the
investigation on the mechanism of
regenerating process. | en |