H_2S通过上调HO-1表达保护坏死性小肠结肠炎大鼠肠黏膜  

Hydrogen sulfide protects intestinal mucosa in a neonatal rat model of necrotizing enterocolitis by upregulating the expression of HO-1

作　　者：曾照军[1] 钟森[1] 王家宁[2] 唐俊明[2] 张蕾[2] 王金堂[1] 赵旸[1] ZENG Zhaojun;ZHONG Sen;WANG Jianing;TANG Junming;ZHANG Lei;WANG Jintang;ZHAO Yang(Department of Pediatrics,Renmin Hospital of Shiyan,Hubei University of Medicine,Shiyan 442000,Hubei, China;Clinical Research Institute,Renmin Hospital of Shiyan,Hubei University of Medicine,Shiyan 442000,Hubei, China)

机构地区：[1]湖北医药学院附属人民医院儿科,湖北十堰442000 [2]湖北医药学院附属人民医院临床医学研究所,湖北十堰442000

出　　处：《临床儿科杂志》2017年第2期138-142,共5页Journal of Clinical Pediatrics

摘　　要：目的观察新型外源性硫化氢(H2S)供体GYY 4137对坏死性小肠结肠炎(NEC)大鼠肠黏膜的保护作用,并探讨其可能的作用机制。方法取60只健康新生SD大鼠,随机分成4组。正常对照组,不施加任何干预;NEC模型组,通过人工喂养、缺氧、冷刺激、脂多糖方法制备NEC模型;H_2S干预组,在NEC模型的基础上,腹腔注射H2S供体GYY 4137;血红素加氧酶-1(HO-1)抑制剂组,在H_2S干预组已有干预的基础上,腹腔注射HO-1抑制剂Znpp。于试验第4天处死大鼠,取回盲部肠管进行苏木精-伊红(HE)染色并作组织病理学评分;检测各组新生鼠小肠组织中丙二醛(MDA)及超氧化物歧化酶(SOD)含量,肿瘤坏死因子α(TNF-α)水平以及肠道组织HO-1表达。结果 4组新生大鼠肠组织病理评分的差异有统计学意义(P<0.001),NEC模型组的病理评分最高,其次为HO-1抑制剂组、H_2S干预组。NEC组病理评分≥2,表明建模方法有效。NEC组与对照组相比,MDA及TNF-α含量明显上升,T-SOD含量下降,差异有统计学意义(P<0.05);H_2S干预组同NEC组相比,MDA及TNF-α含量明显降低,T-SOD含量明显升高,HO-1表达增加,差异有统计学意义(P<0.05);HO-1抑制剂组较H_2S干预组相比,MDA及TNF-α含量明显升高,T-SOD含量降低,差异有统计学意义(P<0.05)。结论新型H2S供体GYY 4137能够有效保护NEC大鼠肠黏膜,降低MDA及TNF-α的含量,增加T-SOD的含量;其保护作用可能与上调HO-1蛋白的表达有关。Objective To explore the protective effects of GYY4137, a new hydrogen sulfide donor, on intestinal mucosa in a neonatal rat model of necrotizing enterocolitis (NEC), and its potential mechanism. Methods Sixty SD rats were randomly assigned into 4 groups: group A (control group), group B (NEC group), group C (NEC with GYY4137 treatment,H2S donor group), and group D (NEC with GYY4137 and Znpptreatment, HO-1 inhibitor group). The SD rat models of NEC were established using simulated milk feeding-hypoxia-cold stress-Lipopolysaccharides. The injury degree of intestinal mucosa was evaluated using HE-staining, and its mechanisms were investigated using biochemical indicators and Western blotting.Results Compared with control group, the pathology score and the total superoxide dismutase (T-SOD) in the NEC groupwas significantly higher, the concentrations of methane dicarboxylic aldehyde (MDA) and necrosis factor α (TNF-α) werelower(P<0.05). Compared with those in NEC group, the pathology score and the concentration of MDA and TNF-α in the H2Sdonor group were significantly lower, the T-SOD, and the HO-1 expression was higher. The pathology score and the level ofMDA and TNF-α were significantly increased after treated with HO-1 inhibitor Znpp, and T-SOD was significantly decreased..Conclusions The GYY4137, as a new H2S donor, could attenuate the injury of intestinal mucosa in a neonatal rat model of NEC by upregulating the expression of HO-1.

关 键 词：坏死性小肠结肠炎 硫化氢 血红素加氧酶-1 大鼠 

分 类 号：R725.7[医药卫生—儿科]