IL-6 /STAT3 Signaling Pathway Regulates The Expression Of HMGB1 In Intestinal Tissue Of Rats With Sepsis

Objective:The purpose of this study was to observe the expression of highmobility group proteins1(HMGB1) in intestinal tissue of rats with sepsis through thececum ligation puncture(CLP), to explore whether interleukin-6(IL-6) / signaltransduction and activator of transcription 3(STAT3) pathway regulates the expressionof HMGB1, and IL- 6 monoclonal antibody have protective effect to the septic rats.Methods:120 male SD rats were randomly divided into three groups: sham operationgroup(group S,n=40), CLP group(group C,n=40) and anti-IL-6 monoclonal antibodygroup(group T,n=40). Group S only maked simple laparotomy;Group C and group Twere established rat model of sepsis by using CLP,Group T received intraperitonealinjection of anti-IL-6 monoclonal antibody after one hour,while the equal volume ofSodium lactate ringer’s solution was given in groups S and group C.Animals wereobserved, including response to external stimulus,activity, diet, weight etc andrecorded the number of deaths.Ten rats in each group were sacrificed at 3,12,24 and48 h respectively,and intestinal tissue specimens were removed for pathologicalchanges by HE staining, the activity of plasma diamine oxidase(DAO) and content of Dlactic acid by spectrophotometric,the protein expression of HMGB1 and IL-6 byimmune histochemical,and STAT3-protein by Western-Blot.Results:1. Rats living conditions: Group S rats basicly have no abnormal, 10/10 live within 48 hours. Group C rats after surgery overall have poor livingconditions,the mortality rates of group C rats remain elevated after 12 h, 3/10 live to48 hours.Deaths of group T are obviously lower than that of group C, 6/10 live within48 hours.2.The pathological change of intestinal mucosa:Group S each time have no seesignificant intestinal damage, pathological scores are also no difference( P ﹥0.05).Group C and group T showed significant intestinal damage in different degree,After 12 h injury continues to increase as time delayed.Compared with group S,intestinal mucosal inflammation of group C were obvious at 12 h, 24 h,48 h,intestinalmucosa pathological score were significantly increased(P<0.05).Group T comparedwith group C,intestinal mucosa injury has improved, the pathologic grading decreasedat12 h, 24 h, 48 h(P < 0.05).3. The plasma levels of DAO and D-lactic acid:compared with group S, the activityof Plasma DAO and content of D-lactic acid were significantly increased ingroup C and group T(P < 0.05).Compared with group C, which were significantlylower in group T(P < 0.05).4. Compared with group S, the protein expression of HMGBl, IL- 6 and p-STAT3 of intestinal tissue were significantly increased in group C and group T(p <0.05); howere, compared with group C, the protein expression of HMGBl, IL- 6 andSTAT3 decreased in group T(P < 0.05).5. the relativity analysis of histopathologic grading respectively compared withthe expression of HMGB1 and IL-6: the protein expression of HMGB1 existedpositive correlation with pathological grading of intestine tissue at 12 h,24 h,48 hpoint,the correlation coefficient was 0.572, 0.665, 0.702 respectively(P < 0.05).theexpression of IL-6 existed positive correlation with pathological grading of intestinetissue at 3h、12h,24 h,48h point,the correlation coefficient was 0.505, 0.610, 0.823,0.598 respectively(P < 0.05).Conclusion:1. IL-6, HMGBl involved in intestinal injury in septic rat.2. IL-6/STAT3 signaling pathway can up-regulate the expression of HMGB1 inintestinal tissues of septic rats.; IL-6 monoclonal antibody can reduce the intestinalinjury of septic rat by inhibiting IL-6, and HMGBl.