| Objective:To investigate the pathophysiology of the renal injury and the protective effects on acute renal injury in rats with sepsis,discuss the new ideas for the prophylaxis and treatment of sepsis.Methods:96 cases of healthy and male Wistar rats were randomly divided into 4 groups:normal control group(n=24),sham operation group (sham group,n=24),sepsis group(CLP group,n=24) and treatment group(Cit+CLP groups,n=24). Normal control group without any Processing.Animal in sham group did laparotomy flip cecum after anesthesia,then closed the Peritoneal. Sepsis model was reproduced in sepsis group and treatment group with cecal ligation and puncture (CLP),and the rats of treatment group were given L-citrulline 200mg kg-1 · d-1 for 7 days before operation. The general condition and 48h survival rate were observed at the time point of 6h,12h,24h and 48h after operation.Then the concentrations of serum BUN and Cr, the histopathological changes of kidney were merasured, simultaneously monitored the expression level of TNF-a and IL-6 in kidney tissue by liquid chip technology.Repeated measures ANOVA was used to compare the four groups with respct to continuous variables. The survival curve described by Kaplan-Meier method, and log-rank test were used to analyze the difference survival rate,AP value less then 0.05 was considered as statistical significance. Results:1. The postoperative general condition and 48h survival rate:The normal control group and sham operation group were generally in good condition, and laparotomy without anomaly.Postoperative 12h rats in sepsis and treatment group gradually begin to appear obvious bacteremia, and we find an intra-abdominal abscess exhibiting in rats.But compared to sepsis group, symptoms of infection and cesarean section see alleviated in citrulline treatment group at each time point. The 48h survival rate in sepsis group, citrulline treatment group are 37.5%,70.8%, and the survival rate of the two groups were statistically significant (P<0.05)2. The concentrations of serum BUN and Cr:Serum BUN and Cr concentrations in sepsis group are significantly higher than sham operation group (P< 0.05).and Serum BUN and Cr concentrations are lower than sepsis group at varous time points in treatment group.3.The histopathological changes of kidney:There are no significant pathological changes I in kidneies are observed under light microscope in the control group and sham group.Postoperative 6h,sepsis group and treatment group appear inflammatory kidney changes,and over time futher aggravate,48h of the most significant. Treatment group compared with those in sepsis inflammatory changes in less pathological score (Paller) at each time point.4. The expression level of TNF-a and IL-6 in kidney tissue:Sepsis group in various time points of the TNF-a, IL-6 levels are higher than control group and sham group (P<0.01).TNF-a level rapidly increase in 6h, and begin to decline behind 12h, to a further decline in 24h,48h, (P<0.05). The level of IL-6 increased in 6h, and reach the maximum at 12h thereafter gradually decline (P < 0.05). At each point after CLP. The serum TNF-a and IL-6 levels of treatment group were lower than those of sepsis group, compared with sepsis group had significant difference (P< 0.05) at each phase point after surgery.Conclusions:1. The symptoms of infection and mortality in rats with sepsis can reduced by administering exogenous arginine.2. Citrulline can reduce serum BUN and Cr concentration, improve kidney function and reduce renal histopathological damage in rats with sepsis,is a protective role in sepsis-induced renal injury in rats.3. citrulline inhibits the expression of proinflammatory cytokines TNF-a, IL-6 in renal tissue.Description citrulline may pass regulate cytokines expression level, which is a protection role in the process of the development of sepsis-induced renal injury.But the concrete mechanism need further study. |
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