硫化氢提高肠道微循环灌注保护新生儿坏死性小肠结肠炎

Exogenous H?S up-regulatesintestinalm icrocirculation to protect ratsfrom neonatalnecrotizing enterocolitis

摘要:

探讨硫化氢（H 2 S）对新生 SD 大鼠坏死性小肠结肠炎（NEC）的肠道微循环作用。方法 出生12 h 内的新生 SD 大鼠 10 只仅用于检测 H 2 S 合成酶表达，另 80 只随机分为 4 组：正常对照组、NEC 模型组、NEC+GYY4137 组、NEC+AOAA 组。各组分别予以腹腔注射生理盐水、LPS+ 生理盐水、LPS+GYY4137、LPS+AOAA。通过人工喂养 - 缺氧 - 冷刺激 - 脂多糖（LPS）方法复制新生鼠 NEC 模型。HE 染色、病理评分以及动物显微镜拍实体照片显示肠组织损伤程度，并统计分析各组新生鼠生存时间，采用 FLPI2 激光散斑血流实时成像系统检测各组血流量变化，探讨 H 2 S 对新生鼠 NEC 的肠道微循环保护作用。结果 与模型组比较，当给与 NEC 处理鼠 GYY4137 时其肠组织血流量升高（ <0.05），病理评分降低（ <0.05）；而给予 AOAA 时其病理评分较 NEC 组增加（ <0.05），但肠组织血流量差异并无统计学意义；NEC 组较正常组病理评分增高，血流量降低。末端回肠与全肠组织血流量均值差异无统计学意义。结论 H 2 S（7.5 mg/kg·d）可通过提高肠道微循环血流量保护 NEC，提高 NEC 新生鼠生存率。

Abstract:

To research the effect of H?S on intestinal microcirculation of newborn SD rats with neonatalnecrotizing enterocolitis(NEC).M ethodsTen newborn Sprague-Dewley (SD)ratswere used to detectthe expression ofH?S synthase.EightySD ratswererandomlydivided into4 groups:controlgroup in which theratswere treated with 0.9% NaCl,NEC group in which the ratswere treated with LPS+0.9% NaCl,NEC+GYY4137 group in which the ratswere treated with LPS+ GYY4137 and NEC+AOAA group in which the ratswere treated with LPS+AOAA.GYY4137 isthedonorofH?S and AOAA is the inhibitor of cystathionine β-synthase(CBS).TheNEC modelof SD rats was induced by bottle-feeding, hypoxia treatment, cold stimulation, and lipopolysaccharide (LPS)peritoneal injection for 3 days. Then HE stain, the Histologic Injury Score and photos taken under animal microscope were used to show the injury ofintestinaltissues.W hat'smore,the intestinalmicrovascularblood flow wasdetected by real-time imaging system ofFLPI2 laserspeckle blood flow and the survivaltime ofthe newborn rats was surveyed.The protective effectofH 2 S on intestinalmicrocirculation ofnewborn NEC rats was explored.ResultsCompared with the NEC group,the intestinalmicrovascularblood flow wassignificantly increased and the Histologic Injury Score was significantly decreased in the NEC +GYY4137 group ( < 0.05). Importantly, administration ofAOAA totheNEC ratssignificantlyincreased theHistologicInjuryScore( < 0.05),buttherewas no significantdifference in the intestinalmicrovascularblood flow between the NEC group and the NEC+ AOAA group.W hen compared to the controlgroup,the intestinalmicrovascularblood flow wassignificantly decreased and the Histologic Injury Score wassignificantly increased in the NEC group. Conclusions H 2 S [7.5 mg/(kg·d)]could protectnewborn NEC ratsand increasethesurvivalratebyincreasingblood flow ofintestinalmicrocirculation.