The Expressions And Significances Of Tight Junction Proteins,NOD2 And Related Signaling Molecules In Parenteral Nutrition Rats

Objective:parenteral nutrition(PN)is a life-saving support for patients who unable to utilize their own intestinal tract for nutrition gain.There are several intestinal injuries along with PN administration including a shift in the intestinal microbiome,an increased mucosal proinflammatory state,and a subsequent loss of intestinal barrier function.To date,these injuries are considered to be contributing factors to translocation of intestinally derived bacteria and PN associated liver disease.The exact mechanisms are still on investigation.In this study tight junction proteins(ZO-1,occludin,claudinl),NOD2 and related signaling molecules NF-?Bp65,p-p65,p38MAPK(p38),p-p38,ERK,p-ERK and ERBIN in the rats'intestine of PN group and nomal saline group were detected by western blot,and the mechanisms involved in intestinal injuries were studied,aiming to provide some new ways for clinical prevention and treatment of PN associated complications.Methods:12 SPF male SD rats were randomly divided into NS group and PN group.For each rat,a silicone catheter was inserted into the right jugular vein.All rats were fed for the first two days after surgery,then from the third day on,The NS group were infused saline intravenously,meanwhile,fed with food and water.The PN group were infused lipid emulsions(Table 1 for formula)only.The volume of intravenous fluids are the same.A week later,all rats were sacrificed,liver and intestine were harvested immediately.First,the height of intestinal mocusa and vilus were analyzed using microscope and levels of tight junction proteins ZO-1,occludin,claudinl in the intestine were detected by western blot.Second,NOD2 and related signaling molecules,including NF-KBp65,p-p65,p38,p-p38,ERK,p-ERK and ERBIN in the intestine were detected by western blot.Using immunohistochemical staining to analyze the levels of p-p65 in the intestine.Results:1.The height of intestinal mocusa and vilus of PN group were significantly decreased compared with NS group(P=0.004,P=0.007).The expression levels of ZO-1,occludin of PN group was significantly decreased than that of NS group(P<0.01,P<0.01).There was no significant differences of the expression levels of claudinl between the two groups(P>0.05).2.The expression levels of NOD2 of PN group was significantly increased than that of NS group(P=0.003).The expression levels of NF-?Bp65 and the ratio of p-p65:p65 in PN group was significantly increased compared with that of NS group(P=0.01,P=0.046).The expression levels of p38 of PN group was significantly decreased than that of NS group(P=0.012).The ratio of p-p38:p38 in PN group was significantly increased compared with that of NS group(P=0.046).The expression of ERK,the ratio of p-ERK:ERK and ERBIN had no significant differences between the two groups(P>0.05).Immunohistochemical staining showed the expression level of p-p65 was increased in PN group compared with that of NS group(P=0.048).Conclusion:1.Administrationof parenteral nutrition comes with the intestinal mucosal atrophy,down-regulation of ZO-1 and occludin,which implying breakdown of tight junction.2.Administration of parenteral nutrition accompany with up-regulation of NOD2.The ratio of p-p65:p65 and p-p38:p38 increased with the administration of parenteral nutrition.