Effects of Kuijieling on Intestinal Mucosal Repair and Intestinal Autophagy in Ulcerative Colitis Rats Based on TLR4-NOD Signaling Pathway

ZHOU Guangquan; LI Kun; JI Yu

doi:10.3969/j.issn.1002-3429.2024.02.018

Abstract：Objective To investigate the effects of Kuijieling on intestinal mucosal repair and intestinal autophagy in ulcerative colitis(UC)rats based on Toll-like receptor 4(TLR4)-nucleotide-bound oligomeric domain-like receptor(NOD)signaling pathway.Methods A total of 60 rats were divided into normal group,UC group(model group),and low-dose,medium-dose and high-dose Kuijieling groups,with 12 rats in each group.Except the normal group,the other four groups were given 2,4,6-trinitrobenzene sulfonic acid and ethanol solution enema to prepare UC model.The normal group and UC group were given the same amount of normal saline,and the low-,medium-and high-dose Kuijieling groups were given the same amount of Kuijieling 1.85 g/kg,3.70 g/kg and 7.40 g/kg,respectively,once a day for 12 consecutive weeks.Disease activity index(DAI)score,colon length,and colon mucosal damage index(CMDI)score in each group were analyzed.Ser-um D-lactic acid(D-LAC),diamine oxidase(DAO),serum and colon tissue tumor necrosis factor-α(TNF-α)were detected using detection kit.Lactulose(L)and mannitol(M)were detected,for calculating urine L/M.Western blot assay was used to detect the expressions of autophagy-related protein Beclin1,autophagy-related gene 5(ATG5),TLR4,TLR2 and NOD-like receptor protein 3(NLPR3)proteins in colon tissue.Results Compared with normal group,DAI scores in the UC group was higher at 1,2,6 and 12 weeks after treatment,and compared with UC group,DAI scores in low-,medium-and high-dose Kuijieling groups was significantly decreased at 1,2,6 and 12 weeks after treatment(P＜0.05).Compared with normal group,colon length in UC group was significantly shortened,CMDI score,serum D-LAC and DAO,urinary L/M values,TNF-α in serum and colon tissue,and TLR4,TLR2,NLPR3 protein expressions in colon tissue were significantly increased,and Beclin1 and ATG5 in colon tissues were significantly decreased(P＜0.05).Compared with UC group,colonic length was significantly prolonged in low-,medium-and high-dose Kuijieling groups,Beclin1 and ATG5 protein expression was signifi-cantly increased.CMDI score,serum D-LAC and DAO,urinary L/M values,TNF-α in serum and colon tissue,and TLR4,TLR2,NLPR3 protein expressions were significantly decreased(P＜0.05).There were statistically significant differences in the above indexes among low-,medium-and high-dose Kuijieling groups in a dose-effect manner(P＜0.05).Conclusion Kuijieling can improve intestinal autophagy in UC rats by regulating TLR4-NOD signaling pathway,alleviate colon tissue in-flammation,and facilitate intestinal mucosal repair,and the effect of high-dose group was better.