The Effect Of Malnutrition On Plasma ACTH And Corticosterone During Early Sepsis In Rats

Objective:To observe the changes of plasma ACTH and corticosterone during the early course of sepsis in the immunocompromised rats caused by malnutrition.Methods:126 male Sprague-Dawley rats were randomly divided into well-nourished group(WN,n=62)and malnutrition group(MN,n=62).Malnutrition group was set up to receive water ad libitum and 9g food per day,corresponding to one-third of the estimated daily food consumption.Well-nourished group was set up to receive water and food ad libitum.All rats were housed in individual cages for 4 weeks.After 4 weeks,spleen and thymus were removed from 6 rats of each group after being euthanized,weighed,and prepared for histological analysis.Thirty rats in each group of WN and MN were used for survival analysis.The animals of WN and MN were randomly divided into well-nourished-CLP group(WNC,n=16),well-nourished-sham group(WNS,n=10),malnutrition-CLP group(MNC,n=18)and malnutrition-sham group(MNS,n=10).The rats in the WNC and MNC were assigned to undergo cecal ligation and puncture(CLP)surgery.Whereas the rats in the WNC and MNC were assigned to undergo sham surgery.Blood collection from the abdominal aorta at 8 h and 16 h after sham or CLP surgery.IL-1?,IL-10,ACTH and corticosterone levels in plasma were measured by ELISA.The adrenal glands were harvested and the histological structure,macrophage distribution and apoptosis of the adrenal gland were observed.Analysis the percentages of CD3+,CD4~+and CD8~+T cells and M1-type macrophages(CD11b/c~+CD80~+,CD11b/c~+CD86~+)in spleen by flow cytometry.Results:Malnourished animals showed a loss of spleen,thymus and body weight when compared with well-nourished animals.Compared to well-nourished-CLP group,malnutrition-CLP group exhibited dramatically increased mortality(100%vs 65%after CLP-induced sepsis,p<0.001).Before CLP surgery,the percentages of CD4~+,CD11c~+CD80~+and the ratio of CD4~+/CD8~+in the malnourished animals were increased when compared with those in well-nourished animals(P<0.05,P<0.01,P<0.05).However,after CLP surgery,the percentage of CD4~+,CD8~+and the ratio of CD4~+/CD8~+of the malnourished and well-nourished animals did not change when compared with their respective basic status.After CLP surgery,the abundance of M1-type macrophages(CD11c~+CD80~+,CD11c~+CD86~+)of the well-nourished group was significantly increased compared with their basic status(P<0.01),while the abundance of M1-type macrophages of malnourished rats did not change compared with their basic status.Compared with the well-nourished sham group,the plasma ACTH level of well-nourished CLP group did not change at 8h and 16h after surgery,but the plasma corticosterone level significantly increased at 8h(P<0.05),and significantly decreased at 16h(P<0.01).Compared with the malnourished sham group,the plasma ACTH level of the malnourished CLP group did not change at 8h,and increased at 16h(P<0.05),while the plasma corticosterone level did not change at 8h and 16h after surgery.The peak of corticosterone levels in malnutrition-CLP group is lower than those in well-nourished-CLP group(P<0.05).Malnourished and well-nourished rats underwent CLP showed a significant increase in the serum concentrations of IL-1?and IL-10(P<0.01).Nonetheless,the IL-1?and IL-10serum levels were similar in well-nourished-CLP group and malnutrition-CLP group.Furthermore,we observed that compared with well-nourished CLP group,malnutrition-CLP group showed more hemorrhage,macrophage cell infiltration and necrosis in adrenal gland.Conclusion:CLP-induced sepsis resulted in dynamic changes of ACTH,corticosterone levels,and resulted in dysregulation of the HPA axis.Malnutrition can resulted in adrenal insufficiency,and inhibit the increase of glucocorticoid during the early course of sepsis.