The Comparison Of Liver Regenerative Capacity Between The Female And Male Mice

Background and Objective The liver preserves a strong capacity for regeneration, but the statistic data has shown a higher incidence of liver cirrhosis and liver cancer in men when compared with that of women. Some liver diseases are also mainly occurred in men and the mechanism is unknown. Our preliminary experiments found that under the same living environment and experimental conditions,the damage tolerance of male mice was much inferior to the females,which suggesting that a difference may exist in the capacity of self-repair between the mice with different gender after liver injury. Clarifying the internal mechanism of this difference is very important to the clinical individual treatment of liver diseases.Animal experiments have shown that after partial excision of liver,the remaining mature liver cells will proliferate compensately and restore the original liver weight and liver function soon.But when the proliferation capacity of mature liver cells is inhibited,these cells can not regenerate well,then the liver stem cells, which is called oval cells, will be activated to proliferate and differentiate into hepatocytes & biliary epithelial cells. 2-AAF (2-acetylaminofluorene) can inhibit mature hepatocytes to proliferate,and 2-AAF combined with partial hepatectomy(2-AAF+PH) is a classical model for stimulating oval cells proliferation.In our study, both PH model and 2-AAF+PH model were established and the regeneration of mature liver cells and oval cells in different time points after PH were observed. The liver regeneration capacity was compared between the mice with different gender to expore the relationship between liver regeneraton and the gender.Methods 120 adult KunMing mice (both males and females are 60) were randomly divided into PH group and 2-AAF+PH group.In PH group, the mice were subjected to PH, which will remove 2/3 of the liver;in 2-AAF+PH group,the mice were fed with 2-AAF for 5 days and then subjected to PH. Liver tissue in two groups were collected at 1d, 3d,5d,7d,10d and 14d respectively after PH. The body weight and liver weight were figured out before and after hepatecomy, the liver regeneration rate were then calculated. The liver regeneration rate, BrdU labeling index and PAS staining scores were assessed and compared between the mice with different gender in each model at every time point after PH.Results1. Comparison of liver regeneration rate:there is no significant difference between different gender at each time point in PH group;In 2-AAF+PH group,female mouse liver regeneration rate is higher than male mouse at 7d and 10d (P<0.05), and there is no significant difference can be found in the other time points (P>0.05).2. Comparison of BrdU labeling index: there is no significant difference between different gender at each time point in PH group.In 2-AAF+PH group,a significant difference can be found in BrdU labeled hepatic non-parenchymal cells, the male mice have a higher labeling index than that of female mice at 1d,3d and 5d (P <0.01),female mice have a higher labeling index than that of male mice at 10d(P <0.01).The BrdU labeled parenchymal cells are much difference in all time points and the female mice posses higher labeling indexex (P <0.01). Female mice have much more BrdU-positive labeled cell masses than that of male mice at 3d,5d and 7d a (P <0.05).3. Comparison of the relative PAS staining scores: there are significant difference between different gender at each time point in PH group,except for 7d, males are much higher than females at 1d and 14d(p<0.01),females are higher at 3d,5d and 10d(p<0.01).In 2-AAF+PH group, females are much higher than males at each time point(p<0.05).Conclusion1. A remodeling model of mouse partial hepatectomy has been established.2. There is no significant difference in liver regeneration capacity between different gender in PH group at every time point after operation.Both the male and female mice can complete the liver regeneration at 7d to 10d after PH.3. After feeding with 2-AAF before PH,the proliferating cells in liver are mainly hepatic oval cell and other non-parenchymal cells. The male mice have an earlier regenerative reaction at the early stage postoperation,but they needs more time to complete the regeneration process than female mice. The results indicate that the male mice are more sensitive to the stimuli from outside,but their regeneration capacity is inferior to female mice.4. The glycogen synthesis capacity in female mice is stronger than that of male mice during liver regeneration.