姜黄素对新生鼠坏死性小肠结肠炎模型的抗氧化作用及机制

目的: 观察姜黄素作用于新生鼠坏死性小肠结肠炎(necrotizing enterocolitis,NEC)动物模型的疗效,初步探讨其可能的抗氧化作用机制。方法: 健康新生SD大鼠24只,随机分成3组,每组8只。Ⅰ组:NEC模型组;Ⅱ组:姜黄素干预组;Ⅲ组:正常对照组。采用三因素联合造模法。姜黄素干预组实验动物以腹腔注射进行干预。实验动物每日定时称量体重,观察并记录动物生长发育及一般情况。实验结束后进行肠组织标本大体观察及HE染色后组织损伤评分,测定肠组织中丙二醛(MDA)及超氧化物歧化酶(SOD)含量,免疫组化法检测肠道组织血红素加氧酶(HO-1)的表达。结果: Ⅱ组大鼠的生长发育、一般情况及肠组织大体形态改善均优于Ⅰ组。HE染色组织损伤评分显示Ⅰ、Ⅱ组均高于Ⅲ组,比较有统计学差异(P<0.05),Ⅰ、Ⅱ组比较差异有统计学意义(P<0.05)。MDA含量在Ⅰ、Ⅱ组较Ⅲ组明显升高,而Ⅱ组低于Ⅰ组(P<0.05)。SOD活性Ⅰ组较Ⅱ组 和Ⅲ组显著下降(P<0.05),Ⅱ组与Ⅲ组比较差异无统计学意义。HO-1表达Ⅰ、Ⅱ组较Ⅲ组均明显上调(P<0.05),而Ⅱ组较Ⅰ组明显下降,差异具有统计学意义(P<0.05)。结论: 姜黄素是治疗NEC新生大鼠模型的有效药物。姜黄素可能通过诱导NEC实验动物肠黏膜HO-1的表达而发挥其对肠道组织的保护作用。

The effect and possible mechanism of curcumin on experimental necrotizing enterocolitis

AIM: To observe effects of curcumin on oxidative damage in intestines of newborn rats with necrotizing enterocolitis (NEC) , as well as investigate the potential mechanism of NEC. METHODS: Twenty four Sprague-Dawley (SD) rats were randomly divided into 3 groups right after birth. Rats in the groupⅠwere subjected to formula feeding, cold stress, hypoxic-reoxygenation treatment as well as LPS intragastric administration. NEC intestinal damage was evaluated by histological scoring. Animals in group II were managed according to the same way except the intraperitoneal injection with curcumin. Rats in Group Ⅲ were delivered naturally and were dam fed. All rats were weighed every day and sacrificed on the 4th day. Proximal intestines of ileocecal junction were undertaken pathological sectioning and evaluated for pathological scoring by hematoxylin and eosin (HE) staining. The activity of intestines malonaldehyde (MDA),superoxide dismutase (SOD) and the expression of heme oxygenase-1(HO-1) in all rats were also detected respectively. RESULTS: Compared with group Ⅲ, rats in groupⅡshowed better growing development, improved physical activity and milder intestine gross characteristics than groupⅠeven after the same stress. The pathological scores were significant different among these three groups (P<0.05). Intestinal MDA concentration increased with the severity of intestine injure (P<0.05). SOD activities of group I and II decreased than that of group III. There was a significant difference in the first two groups (P<0.05). The expression of HO-1 was significant increased in groupⅠand group Ⅱ.The difference between the two groups was statistical significant (P<0.05).CONCLUSION: Curcumin could alleviate the intestinal injure in the experimental necrotizing enterocolitis rats. The potentional mechanism might be reducing intestinal oxidative damage through upregulating the expression of HO-1, decreasing MDA concentration as well as enhancing the activity of SOD.