Cecal Ligation And Puncture Sepsis Rats Induced Intestinal Damage And Changes In Neuropeptide And Its Related Research

Objective: The study was performed to dynamically observe the changes of theintestinal injury and the serum tumor necrosis factor (TNF-alpha), interleukin-1(IL-1),calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) of rats induced bysepsis, and to briefly discuss their correlation and possible mechanism.Methods: SD rats66, male or female, were randomly divided into three groups:(1)normal control group (group A, n=6), sham operation group (group B, n=30), sepsisgroup (C, n=30);(2) Group A animals were got blood sample from abdominal aortaafter anesthesia and weighing, and we used the way of enzyme-linkedimmunosorbent to detect of the levels of diamine oxidase (DAO),tumor necrosis factor(TNF-a),interleukin-1(IL-1),calcitonin gene-related peptide(CGRP) and neuropeptideY(NPY), then took the terminal ileum to exam intestinal mucosal pathological change.(3) Group B animals were carried out the same steps with the normal control group aftercecal exploration operation. The blood sample was got respectively at the time point of3h,6h,12h,24h and48h, and then took the terminal ileum tissue to exam intestinalmucosal pathological change at the same point. Each phase point had6rats.(4) GroupC animals were taken the same steps with the normal control group after CLP surgery.The blood sample was got respectively at the time point of3h,6h,12h,24h and48h,and then took the terminal ileum tissue to exam intestinal mucosal pathological changeat the same point. Each phase point had6rats.Result:1. The level of serum DAO increased after CLP3h in sepsis group. The difference wasstatistically significant compared with the normal control group and sham group (p<0.05), and the level of serum DAO gradually increased to the highest values at48h point (1.47±0.02pg/ml), higher than the normal control group and sham group (p<0.05). The comparison of each time point in normal control group and sham group wasnot statistically significant (p>0.05).2. The sepsis rat serum TNF-α level was significantly higher than the normal controlgroup and sham operation group (p <0.01), reached its peak(390.94±27.70pg/ml) at24h point, then downward trend, but still significantly higher than the normal controlgroup and sham operation group (p <0.01); the serum IL-1level began to increase(221.40±8.06pg/ml) after CLP3h, it was significantly higher than the control groupand sham group (p<0.05), reached its peak (253.21±4.54pg/ml)at6h point, thendownward trend, but still higher than the normal control group and sham group (p<0.05). The comparison of each time point in normal control group and sham group wasnot statistically significant (p>0.05).3. The serum level of CGRP was significantly reduced after CLP at the3h point insepsis group (80.87±4.65pg/ml),the difference was statistically significant comparedwith normal control group and sham group(p <0.05), and the serum level followed bygradually increasing, but still lower than normal group at48h point (171.36±6.12pg/ml); serum NPY level increased significantly after CLP at3h point(548.25±8.49pg/ml), the difference was statistically significant compared with normalcontrol group and sham group(p <0.05), then decreased gradually, but was still higherthan the normal group at48h point (313.00±10.63pg/ml).4. The intestinal tissue pathology showed that the intestinal mucosa of the normalcontrol group had structural integrity and the intestinal villus arranged in neat rows. Theintestinal pathological change of sham operation group was similar with the controlnormal group. Intestinal villus arranged chaos, shortening or blunting after CLP.Epithelial cell became degeneration and necrosis significantly, and the submucosa hadthe form of interstitial edema.5. All data took the form of “mean±standard deviation”, using the SPSS13.0statistical package for analysis, and correlation analysis used Spearman rank correlation analysis.1) TNF-α and DAO have a significant positive correlation, the correlation coefficientwas.897, P <0.01; IL-1and DAO have a significant negative correlation, the correlationcoefficient was-0.679, P <0.01.2) CGRP and DAO have a significant positive correlation, the correlation coefficientwas.904, P <0.01; NPY and DAO have a significant negative correlation, the correlationcoefficient was-0.974(P <0.01)3) and TNF-α and CGRP have a significant positive correlation, the correlationcoefficient was0.756, P <0.01, TNF-α and NPY have a significant negative correlation,the correlation coefficient was-0.860, P <0.01; IL-1and CGRP have a significantnegative correlation, the correlation coefficient was-0.859, P <0.01, IL-1and NPY havea significant positive correlation, the correlation coefficient was0.742, P <0.01.Conclusion:1. In the process of the pathogenesis of sepsis in rats, serum DAO level increased withthe course of development. Septic rats got the gastrointestinal mucosal injury, and theinjury had been increasing.2. In the process of gastrointestinal injury serum TNF-α、 IL-1and otherinflammatory cytokines might be involved in intestinal mucosal injury in septic rats.3. The serum level of CGRP declined abnormally and the level of NPY rised abnormallyin sepsis rats, these could cause blood circulation disorders of the gastrointestinal tract.It may be one of the reasons about gastrointestinal mucosa injury.4. When sepsis caused gastrointestinal mucosal injury, the abnormal changes of serumCGRP and NPY might be related to inflammatory factors in a large number of therelease in septic rats.