The Value And Possible Mechanism Of Curcumin In Treating Necrotizing Enterocolitis Rat Model

PartⅠRESEARCH OF THE RELATIONSHIP BETWEEN THE TOLL-LIKE-RECEPTOR 4 EXPRESSION LEVELS IN NEWBORN RATS'INTESTINAL MUCOSA AND INCENDENCE OF NECROTIZING ENTEROCOLITISObjectiveObserve the expression of TLR4 on different day-old rats'intestinal mucosa and the development of necrotizing enterocolitis, to discuss the relationship between the TLR4 expressive levels in the intestinal mucosa and incendence of necrotizing enterocolitis.Methods48 newborn S-D rats were randomly divided into six groups, group A,group B and group C were put to death respectively on 1-day-postnatal, 3-day-postnatal and 7-day-postnatal ,and proximal intestines of ileocecal junction were undertaken pathological sectioning. The expression of TR4 was detected by immunohistochemical method. Group D,group E and group F on 1-day-postnatal,3-day-postnatal and 7-day-postnatal were established by artificial feeding , cold exposure after hypoxic-reoxygenation treatment and LPS intragastric administration respectively. All the subjects were put to death on a day after modeling and the proximal intestines of ileocecal junction were undertaken pathological sectioning meanwhile. HE dyeing was carried out to observe histological changes ,make a score of tissue damage and add up incidence of NEC.ResultsThe expression of TLR4 in different day-old rats'intestionnal mucosa: group A: 5.44±0.03﹥,group B: 5.22±0.24﹥group C: 4.92±0.09,and comparison of TLR4 expression of each group had significant differences (P<0.05). The pathological scores for each gourp were group D: 3.42±0.61﹥group E: 2.47±0.39﹥group F: 1.68±0.34, and comparison of each group had significant differences (P<0.05).The incendence of necrotizing enterocolitis for each gourp were group D: 100%(8/8)﹥group E: 62.5%(5/8)﹥group F: 15%(2/8),and comparison of each group had significant differences (P<0.05).ConclusionStudies have shown that newborn rats intestine expressed high levels of TLR4 , however, the expression of TLR4 and incendence of necrotizing enterocolitis decreased significantly with the increasing of age.So we speculate: the expression of TLR4 in intestionnal mucosa and incendence of necrotizing enterocol have a close relationship. Excessive expression of TLR4 plays a critical role in the development of necrotizing enterocol. PartⅡTHE VALUE AND POSSIBLE MECHANISM OF CURCUMIN IN TREATING NECROTIZING ENTEROCOLITIS RAT MODELObjectiveTo discuss the effect of Curcumin and its anti-inflammatory mechanisms in necrotizing enterocolitis rat model.MethodsNEC model of rats were established by artificial feeding,cold exposure after hypoxic-reoxygenation treatment and LPS intragastric administration. The rats were randomly divided into normal control(group A) , model group(group B), curcumine group(group C)and solvent group(group D). All the subjects were put to death on the 4th day and proximal intestines of ileocecal junction were undertaken pathological sectioning. HE dyeing was carried out to observe histological changes and make a score of tissue damage. The expression of TLR4,NF-κB and P38MAPK was detected by immunohistochemical method. Other intestinal tissue was treated into homogenate. After the homogenate was centrifuged,supernates were tested the density of TNF-αand IL-6 with enzyme linked immunosorbent assay. ResultsThere were not NEC symptoms in rats of groups A and D. The rats of group B appeared typical NEC symptoms .Compared with group B the NEC symptoms of group C appeared later and lighter. The histopathologic score and expression of NF-κB,P38MAPK,TNF-αand IL- 6 in group B significantly increased (P<0.05) compared with groups A and D, and group C significantly reduced(P<0.05) compared with group B. The expression of TLR4 in group B and C significantly reduced (P<0.01) compared with groups A and D, and group C slightly increased ((P>0.05) compared with group B.ConclusionCurcumin has a protective effect on rats of NEC. Its mechanism may be the restraint in NF-κB, P38MAPK,TNF-αand IL-6 expressions so as to have an anti-inflammation effect . Because TLR4 protein levels was only tested , so the impact of curcumin on TLR4 can not be determined.