Intervention Mechanisms Of The NF-?B Signaling Pathway With Changhe Decoction In Rat Radiation Enterocolitis

Objective To observe the molecular mechanism of radiation enteritis(RE),and confirm the curative effect of intervention mechanism of the Chinese medicine compound Changhejianye(CHJY),the rats of radioactive enteritis models established induced with linear accelerator show the variation of NF-?B?PPARs?TLR4?inflammatory cytokine in the small intestine of rats in the model group.Intervening with the CHJY,we observe the variation of NF-?B?ROS?TLR4?inflammatory cytokine in the rats small intestine.To confirm the curative effect of CHJY by scavenging oxygen free radical,reducing the NF-?B pathways activated,adjusting the balance of oxidation and anti-oxidation system,and inhibiting the production of inflammatory cytokines.Methods Forty-six male specific pathogen-free Sprague-Dawley rats were grouped randomly as CD group,compound glutamine group,model group and normal control group.Inducing by linear accelerator,the rats of acute radioactive enteritis models were intragastrically administered with corresponding agents for 7 days.Observe the variation of NF-?B P65,TLR4,PPARs,SOD,ROS,GSH-Px and inflammatory cytokine in the rats small intestine on the last day.Results1.Rats changed after irradiation: the rats in each group showed different degrees of diarrhoea and decreased activity compared with the normal group,and the general condition of the model group was the worst.On the 6-8 day after irradiation,body weight,mobility and defecation were normal in all groups except the model control group.The body mass of the normal control group was significantly higher than that of the other three groups(P<0.01).The mass of the CD group and the compound glutamine group higher than the model control group(P<0.01).2.The morphological changes of rats' small intestine in each group: The small intestinal villus of the rats in the administration group were basically complete compared with the normal control group,and no obvious ulcer was found.The small intestine tissue of the model control group was sparse and the gland atrophy and deformation.3.NF-?B signaling pathway and inflammatory factors: compared with the model control group,the expression of TLR4 and NF-?B P65 in the CD group was significantly decreased(P<0.01).At the same time,the contents of IL-1,IL-6 and TNF-? in the small intestinal tissues of the rats were significantly decreased(P<0.01),and the CD group rats were lower than the compound glutamine group(P<0.05).4.Oxidation and anti-oxidant system:Compared with the model control group,the activity of GSH-Px and SOD in the intestinal tissue of the CD group increased significantly(P<0.05),and the expression of ROS decreased significantly(P<0.01).At the same time,there was no remarkable difference in expression of ROS and activity of GSH-Px and SOD in CD group compared with normal group(P>0.05).5.Peroxisome proliferator-activated receptor(PPARs):PPARs showed weak expression in normal situation,PPARs in model control group decreased significantly,the expression of rats in the drug group increased,suggesting that the CHJY could up-regulate the expression of PPARs,thus inhibiting the activation of NF-kappa B signaling pathway and inhibiting the inflammatory response.Conclusion1.Changhejianye can relief symptoms obviously and have therapeutic effect on radiation enteritis rats.2.Changhejianye can protect the intestinal mucosal tissues from oxidative damage caused by radiation,which can reduce inflammation and accelerate tissue repair.3.Changhejianye can inhibit the activation of NF-kappa B signaling pathway significantly in rats with radiative enteritis,reduce the secretion of inflammatory factors,prevent the amplification of inflammatory signals,and further enhance the anti-inflammatory effect by regulating oxidation and antioxidant system and activating PPARs,thus reducing radiation damage and protecting intestinal mucosa.