柚皮素调控NLRP3炎性小体对坏死性小肠结肠炎新生小鼠肠道的保护作用研究  

Protective effect of naringin on intestinal tissues of newborn mice with necrotizing enterocolitis by regulating NLRP3 inflammasome

作　　者：田洪民[1] 王淑屏[2] 王鸿雁[1] 卢宪梅[3] TIAN Hong-Min;WANG Shu-Ping;WANG Hong-Yan;LU Xian-Mei(Department of Pediatrics,Jinan Third Peo-ple's Hospital,Jinan 250132,China)

机构地区：[1]济南市第三人民医院小儿科,济南250132 [2]济南市第三人民医院供应室,济南250132 [3]山东大学齐鲁医院儿科,济南250012

出　　处：《中国免疫学杂志》2021年第10期1196-1200,共5页Chinese Journal of Immunology

摘　　要：目的:探讨柚皮素对坏死性小肠结肠炎(NEC)新生小鼠的肠道保护作用及其分子机制。方法:将新生C57BL/6小鼠按随机数字表法分为正常对照组(Control组)、模型组(NEC组)、柚皮素低剂量组(L-NAR,5 mg/kg)和柚皮素高剂量组(H-NAR,20 mg/kg)。采用缺氧冷刺激+LPS腹腔注射的方法建立NEC模型,正常对照组不做处理。建立NEC模型的同时,柚皮素干预组小鼠给予不同剂量柚皮素腹腔注射,持续干预3 d。观察小鼠大体情况并测量小鼠体重;采用HE染色观察小鼠回盲部肠组织病理学变化并进行评分;ELISA法检测小鼠肠组织中炎症因子IL-6、TNF-α、IL-1β和IL-18的表达水平;qRTPCR法和Western blot法检测小鼠肠组织NLRP3、ASC和Caspase-1 mRNA以及蛋白的表达水平。结果:与Control组比较,NEC组小鼠出现明显的NEC症状,体重明显降低,肠组织病理评分、肠组织炎症因子TNF-α、IL-6、IL-1β和IL-18表达水平以及NLRP3、ASC和Caspase-1等mRNA和蛋白表达水平均明显增加(P<0.05);与NEC组比较,H-NAR组小鼠的NEC症状减轻,体重明显升高,肠组织病理评分、肠组织炎症因子TNF-α、IL-6、IL-1β和IL-18表达水平以及NLRP3、ASC和Caspase-1等mRNA和蛋白的表达水平均明显降低(P<0.05),而L-NAR组小鼠的各项检测指标与NEC组的差异无统计学意义(P>0.05)。结论:柚皮素对NEC新生小鼠的肠道具有保护作用,其机制可能与抑制NLRP3炎性小体活化,降低肠组织炎症反应水平有关。Objective:To explore the protective effect of naringin on the intestinal tissues of newborn mice with necrotizing enterocolitis(NEC)and its molecular mechanism.Methods:Newborn C57 BL/6 mice were divided into normal control group(Control group),model group(NEC group),naringin low-dose group(L-NAR,5 mg/kg)and naringin high-dose group(H-NAR,20 mg/kg)according to the random number table method. The NEC model was established by hypoxic and cold stimulation+LPS intraperitoneal injection,and mice in the normal control group were not treated. When the NEC model was established,mice in the naringin intervention group were given intraperitoneal injection with different doses of naringin for 3 days. The general condition of mice were observed and the body weight of mice were measured;HE staining was used to observe the pathological changes of the ileocecal intestine of intestinal tissue;ELISA method was used to detect the expression of inflammatory factors IL-6,TNF-α,IL-1β and IL-18 in intestinal tissues;qRT-PCR and Western blot were used to detect the mRNA and protein expression levels of NLRP3,ASC and Caspase-1.Results:Compared with the Control group,the mice in the NEC group showed obvious NEC symptoms,and the body mass were markedly decreased,while the intestinal histopathological score,the expression levels of TNF-α,IL-6,IL-1β,and IL-18,and the mRNA and protein expression levels of NLRP3,ASC,and Caspase-1 in intestinal tissue were significantly increased(P<0.05). Compared with the NEC group,the NEC symptoms of the H-NAR group were alleviated,and the body mass was significantly increased,the intestinal histopathological score,the expression levels of TNF-α,IL-6,IL-1β,and IL-18 and the mRNA and protein expression levels of NLRP3,ASC and Caspase-1 in the intestinal tissue were significantly decreased(P<0.05). However,there was no statistically significant difference in the detection indicators of mice between L-NAR group and NEC group(P>0.05).Conclusion:Naringin has a protective effect on the intestinal tissuse of n

关 键 词：柚皮素 坏死性小肠结肠炎 NLRP3炎性小体 炎症因子 

分 类 号：R34[医药卫生—基础医学]