地塞米松干预对缺氧缺血性脑损伤脑组织髓鞘碱性蛋白的影响

目的 探讨地塞米松(dexamethasone,Dex)在缺氧缺血性脑损伤(hypoxic ischemicbrain damage,HIBD)中的作用及可能机制.方法 通过建立大鼠HIBD模型,分为Dex大剂量预处理组、Dex小剂量预处理组、Dex大剂量治疗组、Dex小剂量治疗组、生理盐水组和正常对照组,检测血清及脑组织髓鞘碱性蛋白(myelin basic protein,MBP)、白介素-1β(interleukin-1β IL-1β)、凋亡细胞计数和脑组织病理改变.结果 (1)与生理盐水组比较,不同剂量Dex干预组和治疗组脑组织病变均减轻,表现神经元树突复旧,尼氏体增多;(2)HIBD后3 d生理盐水组血清、脑组织MBP、IL-1β的含量(5.88±0.46,34.25±4.65;127.97±16.60,1060.33±42.22)及脑组织凋亡细胞计数(13.27±0.90,11.05±1.23)较正常对照组(2.01±0.12,10.24±1.75;41.21±4.02,221.10±30.57及0.75±0.17)显著增加,P<0.05;HIBD后7 d生理盐水组上述指标有所降低,但较正常对照组仍显著增高,P<0.05;(3)Dex干预后血清及脑组织MBP、IL-1β的含量:预处理组(4.30±0.73,24.10±3.36和59.89±6.16,393.68±31.46)、治疗组(4.48±0.49,16.98±1.32及50.81±8.32,405.15 ±29.02)较生理盐水组(5.88±0.46,34.25±4.65和127.97±16.60,1060.33±42.22)显著下降,P<0.05;预处理组与治疗组无显著性差异,P>0.05;大剂量组较小剂量组作用更明显;(4)Dex预处理组、治疗组的脑组织凋亡细胞计数(7.92±1.64和8.97±0.81)显著低于生理盐水组(13.27±0.90),P<0.05;预处理组较治疗组下降更为明显,P<0.05;大剂量组较小剂量组作用更明显.结论 血清MBP含量的变化可反映脑白质损伤的程度;Dex可能是通过抑制IL-1β的过度表达,减轻炎症级联反应从而起到脑损伤的保护作用.

Effect of dexamethasone on myelin basic protein (MBP) in brain tissues after hypoxic-ischemic brain damage

Objective To explore the possible mechanisms of the neuroprotective effect of dexamethasone(DEX) on neonatal rats with cerebral bypoxia-ischemia. Methods Sprague-Dawley (SD) pregnant rats were made to hypoxic ischemic brain damage (HIBD) model and randomly divided into: pretreatment groups of different doses (L-Dexl group, H-Dexl group); treatment groups of different doses (L-Dex2 group, H-Dex2 group); isotonic saline group (NS group) and normal group (NOR). The expressions of interleukin-1β(IL-1β) and myelin basic protein (MBP) in serum and brain tissue were measured, the number of apoptosis cells in brain tissue was counted, and the pathological changes of brain tissue in HIBD were observed. Results Compared with the NS group, the pathological changes of brain tissue in the pretreatment and treatment groups with different DEX doses were mild with neuron dendrite involution and Nissl body increase. The contents of MBP, IL-1β in serum and brain tissue in NS group 3 days after HIBD were (5.88 4±0. 46,34.25± 4. 65 ; 127. 97± 16.60,1060. 33±42.22)and the numbers of apoptosis were 13.27±0. 90 and 11.05±1.23, which were significantly higher than the NOR group (2.01±0. 12,10. 24±1.75; 41.21±4. 02,221.10± 30. 57; 0. 75±0. 17,P<0. 05). On 7 days after HIBD, the above parameters were decreased in the NS group, but remained higher than the NOR group (P<0. 05). The contents of MBP and IL-1β in in serum and brain Dex pretreated rats were (4. 30±0. 73,24. 10±3. 36,and 59. 89±6. 16,393. 68±31.46) and those in the treated groups(4. 48±0. 49,16. 98±1.32 and 50. 81±8. 32,405. 15±29. 02) were significantly lower than those in the NS group(5.88±0. 46,34. 25±4. 65 and 127.97±16. 60,1060. 33 ±42. 22,P<0. 05). No significant difference was shown between Dexl and Dex2 groups with the same dose. The apoptosis cell count in DEX pretreated and treated groups(7. 92± 1.64 and 8. 97± 0.81) were significantly less than those in the NS group (13. 27±0. 90, P<0. 05). Compared with thc pretreated groups, levels of apoptosis in treated groups were higher (P<0.05) and was dose dependent. Conclusions Variations of serum MBP reflect the degree of white matter damage. DEX might protect the brain from injury by inhibiting overexpression of IL-1β followed by alleviated systemic inflammatory reactions.