新生大鼠肺出血动物模型的建立及对临床的启示

Pulmonary Hemorrhage Model of Neonatal Rats and Its Clinical Significance

摘要:

目的：建立与临床病因相符的新生大鼠肺出血动物模型并探讨其发病机制。方法：采用出生4～7 d的Wistar新生大鼠40只，随机分4组。A组为正常对照组，置于25℃恒温环境中。其余大鼠放入氧浓度为5%～6%的有机玻璃箱内，并将该箱放入(10±1)℃冰箱中。按置放时间分为：低温缺氧1 h组(B组)；低温缺氧 2 h 组(C组)；低温缺氧4 h组(D组)，将此3组新生大鼠分别于1，2，4 h后取出并迅速放入置于水浴箱中的有机玻璃箱内，维持箱温37 ℃，供氧使箱内氧浓度达 99.5%～100%，3组均持续2 h。断头法处死动物，肉眼观察肺出血情况，将结果分成5级：Ⅰ级正常肺；Ⅱ级肺水肿；Ⅲ级点状肺出血；Ⅳ级局灶性肺出血；Ⅴ级弥漫性肺出血。结果：① 4组 大鼠处理前，复温前及复温后的肛温差异无显著性(P>0.05)。②肺部大体改变A组为Ⅰ级，B组为Ⅰ～Ⅲ 级，C组为Ⅰ～Ⅴ级，D组为Ⅲ～Ⅴ级，经RIDIT 分析，C组与A组，D组与A、B、C 3组间差异有显著性(P<0.05或 0.01)。③光镜与电镜下肺大体病理改变为Ⅲ～Ⅴ级者，于肺泡内均可见从少量到大量的红细胞，Ⅳ及Ⅴ级尚可见毛细血管基底膜受损或断裂，其改变与新生儿肺出血病理改变相符。结论：采用出生7 d内新生大鼠，给予低温缺氧后再复温供氧，可成功制作与临床病因相似的新生大鼠肺出血模型，其中以低温缺氧4 h后复温供氧2 h组病变最明显。

Abstract:

OBJECTIVE: To establish the pulmonary hemorrhage model in neonatal rats, which corresponds with the clinical etiology, and to explore its clinical significance. METHODS: Forty 4-7 day newborn Wistar rats were randomly assigned into four groups: one control group (Group A) and three hypothermia hypoxia groups. Group A rats were placed in an environment of 25℃, and the three hypothermia hypoxia groups were put into an organic glass box, the oxygen concentration of which was 5%-6%. The box was put into a refrigerator of (10±1)℃. According to the time of refrigeration, the rats were assigned into 1 h, 2 h and 4 h hypothermia hypoxia groups (Group B, Group C and Group D, respectively). They were taken out of the refrigerator after 1 h, 2 h and 4 h respectively and then were put into the organic water bath box within which the oxygen concentration remained 99.5% -100% for 2 h. After the rats were sacrificed, the degree of pulmonary hemorrhage was observed and then the gross anatomical findings were divided into five grades: Grade Ⅰ (normal lung), Grade Ⅱ (pulmonary edema), Grade Ⅲ (spotty pulmonary hemorrhage), Grade Ⅳ (local pulmonary hemorrhage) and Grade Ⅴ (diffuse pulmonary hemorrhage). RESULTS: ①There was no difference in the rectal temperature of the four groups before applying hypothermia, before rewarming and after rewarming. ②The pathologic changes of the lungs in Group A revealed Grade Ⅰ, Grade Ⅰ-Ⅲ in Group B, Grade Ⅰ-Ⅴ in Group C and Grade Ⅲ-Ⅴ in Group D. By the RIDIT analysis, a significant difference was found between Group C and Group D and between Group D and Group A, Group B or Group C (P< 0.05 or 0.01 ). ③Under the light and electron microscope, red blood cells were found in alveoli of the Grade Ⅲ-Ⅴ rats; the damage or breakage of the capillary basal membrane appeared in Grade Ⅳ-Ⅴ rats. These changes were found to correspond with the pathologic changes of neonatal pulmonary hemorrhage. CONCLUSIONS: The pulmonary hemorrhage model of neonatal rats, which corresponds to clinical etiology, can be established with 7 day newborn rats by rewarming and reoxygenating following hypothermia and hypoxia. The best effect comes from the group of hypothermia hypoxia for 4 h.