摘要
目的探讨内皮素-1(endothelin-1,ET-1)受体拮抗剂——波生坦能否阻断肺出血的形成。方法生后7~8 d的Wister新生鼠106只,随机分为空气组(C)10只、实验组和波生坦组各48只,实验组和波生坦组再分别分为4个亚组:缺氧组(H)、低温缺氧组(HH)、低温缺氧后常氧复温组(HHR)和低温缺氧后高氧复温组(HHRO2)各12只,波生坦组预防性给予波生坦。C组置常温室内,H组缺氧6 h(FiO2 5%~6%),HH组低温缺氧(FiO2 5%~6%,10℃±1℃)6 h,HHR组同上低温缺氧,随后常氧下复温2 h,吸入空气,HHRO2组同HHR组但复温时吸入高浓度氧(FiO2>95%)。各组取肺组织,观察肺大体改变,放射免疫法检测实验组肺组织中ET-1含量。结果实验组死亡13例,波生坦组死亡5例,两组死亡率差异有统计学意义(χ2=4.376,P<0.05);实验组中各亚组ET-1含量均显著增高,与正常组比较,P均<0.01;实验组肺大体改变包括肺水肿、肺出血,波生坦组肺大体病理改变减轻,肺出血程度减弱,其中HHR和HHRO2亚组的病理分级与实验组中的HHR和HHRO2亚组相比,差异有统计学意义(Z=2.614、2.940,P均<0.05)。结论 ET-1受体拮抗剂——波生坦能减轻肺出血程度。
Objective To explore if bosentan,an endothelin-1(ET-1) receptor antagonist,can block pulmonary hemorrhage in newborn rats.Methods A total of 106 Wistar newborn rats were randomly divided into 3 groups: control group(group C,n = 10),experimental group(n = 48) and bosentan group(n = 48).The rats in experimental and bosentan groups were randomly divided into four subgroups respectively: subgroup H(n = 12),subgroup HH(n = 12),subgroup HHR(n = 12),subgroup HHRO2(n = 12).Rats in bosentan group were administered intragastrically with bosentan.Group C were exposed to normothermia and normoxia,group H to hypoxia(5%-6 % O2) for 6 hours,group HH to hypothermia(10℃ ± 1℃) and hypoxia for 6 hours,group HHR to hypothermia and hypoxia for 6 hours followed by hyperthermia(37℃) and normoxia for 2 hours,group HHRO2 to hypothermia and hypoxia for 6 hours followed by hyperthermia and hyperoxia( 95% O2) for 2 hours.The gross anatomic changes of rat lungs were observed.ET-1 in pulmonary tissues of the experimental group was measured by radioimmunoassay.Results Five rats and 13 rats died in bosentan group and experimental group,respectively,which had a significant difference in mortality rate between the two groups(χ2 = 4.376,P 0.05).ET-1 elevated significantly in all experimental groups(P 0.01).Pulmonary edema and hemorrhage were the major gross anatomic findings in experimental groups.Attenuated changes including less pulmonary hemorrhage could be observed in bosentan group.There were significant differences in gross anatomical changes between subgroups HHR,HHRO2 of experimental group and their matched subgroups in bosentan group(Z = 2.614 and 2.940,respectively,all P 0.05).Conclusions Bosentan,an ET-1 receptor antagonist,can attenuate the pulmonary hemorrhage in newborn rats.
出处
《临床儿科杂志》
CAS
CSCD
北大核心
2010年第11期1073-1076,共4页
Journal of Clinical Pediatrics
基金
广西科学基金资助项目(No.桂科自0728157)
关键词
波生坦
内皮素-1
肺出血
大鼠
bosentan
endothelin-1
pulmonary hemorrhage
rat