单次地塞米松治疗对实验性脑出血后肺、脑组织的保护作用及机制

The Protective Effects of Dexamethasone Single Administration on the Brainand Lung after Intracerebral Hemorrhage

目的研究单次地塞米松(Dex)治疗对脑出血(ICH)后肺、脑组织的保护作用及可能机制。方法采用立体定向技术自体血尾状核注入法制备SD大鼠ICH模型,将大鼠分为假手术组、ICH模型组和Dex治疗组。采用HE染色观察血肿周围组织与肺组织的炎症反应情况,采用透射电镜观察各组肺组织超微结构变化。采用RT-PCR法半定量检测NF-κB p65 mRNA及糖皮质激素受体α(GRα)mRNA在脑与肺中的表达情况。结果(1)ICH模型组脑水肿明显,血肿周围炎症反应重,肺组织损伤以间质性肺炎表现为主,肺泡结构破坏;Dex治疗组脑水肿较ICH模型组明显减轻,肺组织炎性反应减少。(2)NF-κB p65 mRNA表达,ICH模型组脑出血后血肿周围脑组织(0.44±0.08)和肺组织(0.69±0.16)均较假手术组(分别为0.27±0.05和0.26±0.04)增高(P<0.01),Dex治疗组脑(0.1 7±0.14)及肺(0.17±0.03)组织中NF-κB p65 mRNA均明显低于ICH模型组和假手术组(P<0.01);ICH模型组GRα mRNA表达水平,无论在脑组织(0.47±0.07)还是在肺组织(0.49±0.07)均低于假手术组(分别为0.64±0.03和0.65±0.13)(P<0.01),Dex治疗组脑组织(1.01±0.09)和肺组织(0.89±0.08)GRαmRNA表达较ICH模型组和假手术组均明显增强(P<0.01)。结论 ICH后早期、单次给予Dex治疗可减轻脑组织损害,亦可明显改善继发肺损害,其可能作用机制为Dex提高了GRα mRNA水平并抑制NF-κB p65 mRNA表达。

Objective To study the protective effects of dexamethasone （Dex） single medicated on the brain and lung after intracerebral hemorrhage （ICH）. Methods （1）The ICH model rats were established by infusing autologous blood into the caudate nucleus. Adult SD rats were divided into the sham-operative group （n= 12）, ICH group （n=12）, Dex treated group （n=12）. （2） Inflammation in the cerebral perihematoma and lung was observed by H＆E staining. The ultrastructural changes in pulmonary tissue were observed under electron microscope. （3）Expression of NF-κB p65 mRNA and GRα mRNA in cerebral perihematoma and lung was evaluated by RT PCR. Results （1） Brain edema and the inflammatory cells infiltrating in perihematoma were obvious after ICH; the lung injury was mainly presented as interstitial pneumonia, neutrophile granuloeytes infiltrated which was improved after single Dex treated. （2） NF-κB p65 mRNA level in ICH brain and lung increased dramatically （brain 0. 44±0.08 and lung 0.69±0. 16）, but decreased in Dex group （brain 0.17±0.14 and lung 0. 17±0.03）, even lower than sham-operative group （brain 0.27 ± 0.05 and lung 0.26 ± 0.04） （P〈 0. 01）. The level of GRa mRNA in both brain and lung was reduced significantly after ICH （brain 0. 47±0. 07 and 0.49±0.07） but increased after Dex treated （brain 1.01 ±0.09 and lung 0. 89±0. 08）. Conclusions Dex administration once at early stage after ICH can lessen brain damage and secondary lung injury through increasing GRα mRNA expression and inhibiting the expression of NF-κB p65.