睾酮对脑出血大鼠脑、肺TNF-α、IL-1β含量的影响及可能机制

Effect of testosterone on pathophysiology of lung inflammatory injury following intracerebral hemorrhage

目的探讨睾酮在脑出血大鼠急性脑、肺损伤发生、发展中的作用及可能机制。方法 (1)雄性Wistar大鼠55只,分为对照组、脑出血组和氟他胺预处理组。(2)立体定向技术自体血尾状核注入法制作脑出血大鼠模型;氟他胺预处理组大鼠行氟他胺溶液灌胃(50mg/kg.d)10d后,行脑出血造模;对照组大鼠尾状核注入等量生理盐水。(3)ELISA法测定睾酮及TNF-α、IL-1β含量。(4)HE染色光镜观察大鼠脑、肺病理变化。结果 (1)脑出血组大鼠血清睾酮含量显著升高(P<0.05);而氟他胺预处理组各时相点大鼠血清睾酮含量均显著低于脑出血组(P<0.05);(2)脑出血组大鼠各时相点TNF-α、IL-1β含量较对照组显著增高(P<0.05),而氟他胺预处理组各时相点较脑出血组显著降低(P<0.05)。(3)脑出血组大鼠肺匀浆TNF-α、IL-1β含量亦显著增高(P<0.05),氟他胺预处理组显著降低(P<0.05);(4)脑出血组大鼠脑、肺组织出现明显水肿及炎性改变,氟他胺预处理组大鼠脑、肺组织以上变化明显减轻。结论脑出血大鼠脑损伤同时,出现急性炎性肺损伤,氟他胺预处理后炎性反应明显减轻。提示睾酮含量变化可能与炎性肺损伤密切相关。

Objective To study the effect of testosterone on pathophysiology of lung inflammatory injury,and the possible mechanism following intracerebral hemorrhage.Methods 55 healthy Wistar male rats were randomly divided into the control group,the intracerebral hemorrhage group and the flutamide pre-treatment group.Intracerebral hemorrhage was created in rats by injection of autologous tail artery blood into the caudate nucleus.Flutamide pre-treatment group was pre-treated with flutamide（50mg/kg） by priming stomach for 10 days before getting the blood injection;and the control group was injected with equal amount of sterile saline.Testosterone level in the serum,tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） levels in the brain and lung tissues were determinate by ELISA.Results Serum testosterone level,TNF-α and IL-1β levels in the serum,lungs and brain increased significantly in rats with intracerebral hemorrhage.Flutamide pre-treatment significantly reduced the changes.The brain and lung tissues displayed varied degrees of edema and inflammatory lesions in rat with intracerebral hemorrhage.Conclusion High testosterone content is associated with elevated inflammation and damages to brain and lungs in intracerebral hemorrhage rats.Blockage of testosterone can reverse these adverse effects and protect rats from tissue damages.