摘要
目的通过建立早产动物模型，探讨地塞米松对早产动物脑组织发育的影响和可能机制。方法将18只SD孕鼠应用随机数字表法随机分为3组，大剂量地塞米松组（H—Dex组）；小剂量地塞米松组（L—Dex组）和生理盐水对照组（NS对照组），每组6只。于孕16、17、18d连续3d分别腹腔注射地塞米松0．5mg／（kg·d）、0．1mg／（kg·d）；NS对照组同时刻腹腔注射等体积生理盐水。3组雌鼠均于孕19d剖宫产取出胎鼠制成早产鼠动物模型，留取脑标本，观察脑含水量、脑形态学改变。采用ELISA法及流式细胞术分别检测脑组织髓鞘碱性蛋白（myelinbasicprotein，MPB）、白细胞介素（inter-leukin，IL）-1β含量及脑组织凋亡细胞计数。结果（1）脑含水量：H—Dex组、L—Dex组与NS对照组脑含水量分别为（85．94±0．54）％、（86．08±1．01）％、（86．94±0．82）％，Dex组脑组织含水量较对照组显著下降（P〈0．05）；（2）脑形态学改变：H—Dex组、L—Dex组与Ns对照组比较表现为大脑皮层胶质细胞进一步成熟，且大剂量组比小剂量组变化更为明显；（3）脑组织MBP、IL-1β含量的测定：H—Dex组、L—Dex组、NS对照组脑组织MBP含量分别为（5．73±1．06）μg／mg、（5．46±0．77）μg／mg、（2．42±0.52）μg／mg，Dex组较NS对照组明显增加（P〈0．05），IL-1β含量分别为（249．05±11．29）pg／g、（257．47±9．33）Pg／g、（292．66±21．51）Pg／g，Dex组较NS对照组明显减少（P〈0．05）。H—Dex组与L—Dex组比较差异无统计学意义（P〉0．05）；（4）脑组织凋亡细胞计数：H—Dex组、L—Dex组与NS对照组凋亡细胞计数分别为（18．07±1．63）％、（6．88±0．47）％、（2．00±0．32）％，Dex组较NS对照组明显增加，差异有统计学意义（P〈0．05），且H—Dex组与L—Dex组相比，凋亡细胞计数显著增加。结论（1）预防性应用地塞米松可使大脑皮层胶质细胞进一步成熟，脑组织含水量下降，MBP含量增加，IL-1β含量减少，提示地塞米松具有促进脑白质发育及髓鞘形成，促进脑成熟的作用；（2）地塞米松可致脑组织凋亡细胞计数明显增加，且该作用具有剂量依赖性，提示地塞米松可能对胎脑的正常发育亦有一定负面影响，早产儿应慎用，并倾向于使用小剂量。
Objective By making models of premature animal, explores the effects of dexamethasone on the brain development of premature rats and its mechanisms. Methods Eighteen SD rats were randomly divided into high-dexamethasone（H-Dex） group, low-dexamethasone （L-Dex） group and normal saline（NS） control group,with 6 rats in each group. The pregnant rats in L-Dex group were injected with dexa- methasone [ 0. 1 mg/（ kg. d） ] from 16 to 18 days of pregnancy, while the pregnant rats in H-Dex group were injected with dexamethasone [0. 5 mg/（ kg. d） ] ;the pregnant rats in NS control group were injected with 0. 9% NaCl of the same volume. All of the fetal rats were received after administrating caesarean operation on the day 19 of pregnancy. Rats were sacrificed at the directed time and brain tissue was prepared. Histological feature and the water content of the brains were observed. Level of apoptosis was measured by flow cytometry. The expressions of myelin basic protein（MBP） and interleukin（IL）-1 β in brain tissue homogenate were detected by ELISA. Results （ 1 ） The brain water contents of rats in H-Dex group, L-Dex group and NS control group were （ 85.94 ± 0. 54 ） %, （ 86.08 ± 1.01 ） %, （ 86. 94 ± 0. 82 ） %. Compared with NS control group, the water contents of Dex group were lower （ P 〈 0. 05 ）. （ 2 ） Gliai cells of brain cortex in L-Dex group and H-Dex group were more mature than in NS control group, and the changes in H-Dex group was more significant. （3） The expressions of MBP in brain tissue of H-Dex group, L-Dex group and NS control group were （5.73 ± 1.06） μg/mg, （5.46 ±0. 77） μg/mg and （2. 42 ±0. 52） μg/mg. Compared with NS control group,Dex group was higher （P 〈 0. 05 ）. While the expressions of IL-1β in brain tissue of H-I）ex group, L- Dex group and NS control group were （249. 05 ± 11.29） pg/g, （257.47 ±9. 33） and （292. 66 ±21.51 ） pg/g.Compared with NS control group, Dex group was lower （ P 〈 0. 05 ）. There was no significant difference be- tween H-Dex group and L-Dex group（ P 〉 0. 05 ）. （4） The level of apoptosis in H-Dex group, L-Dex group and NS control group were （ 18.07 ± 1.63 ） %, （ 6. 88 ± 0.47 ） % and （ 2. 00 ± 0. 32） %. Compared with NS control group, the level of apoptosis in Dex group was higher（ P 〈 0. 05 ）, and H-Dex group was higher than that in L-Dex group. Conclusion （ 1 ） Using dexamethasone prophylactic could promote the development of glial cells ,reduce the water content,increase the expressions of MBP, and decrease the expressions of 1L-1β in brain tissues. It indicates that dexamethasone may play a major role in maturation of fetal brain. （2） Using dexamethasone prophylactic could increase the amounts of the apoptosis cells, and this effect is dose-dependent. It indicates that dexamethasone may have a negative effect on the fetal brain and suggestes that using dexamethasone in premature infant should be cautious, and if it has to, using a lower dose.
出处
《中国小儿急救医学》
CAS
2013年第1期69-72,共4页
Chinese Pediatric Emergency Medicine
