阿托伐他汀对脑出血大鼠脑组织NF-κB、TNF-α和IL-1β表达的影响

The Effect of Atorvastatin on the Expression of NF-κB,TNF-αand IL-1β in the Rats with Intracerebral Hemorrhage

目的观察阿托伐他汀对脑出血大鼠血肿周围组织中NF-κB、TNF-α和IL-1β表达的影响,探讨阿托伐他汀对脑出血大鼠的脑保护作用及可能的机制。方法将120只SD大鼠按随机数字表法随机分为假手术组、脑出血组和治疗组。脑出血组和治疗组采用自体血立体定向注射法,建立脑出血动物模型。假手术组于相同部位注射等量0.9%氯化钠注射液。治疗组于术后2h将阿托伐他汀按10mg/kg进行灌胃。于造模后12h、1d、2d、3d和5d分别处死各组大鼠留取脑组织。采用免疫组化法和Western blot法检测各组大鼠脑组织TNF-α、IL-1β及NF-κB的蛋白表达情况。结果与假手术组相比,脑出血组TNF-α、IL-1β和NF-κB的表达增加(P<0.05),均为12h开始持续增加,3d时达高峰,持续表达至5d;与脑出血组相比,治疗组TNF-α、IL-1β和NF-κB的表达减少(P<0.05)。结论脑出血大鼠血肿周围脑组织存在NF-κB、TNF-α和IL-1β的高表达。阿托伐他汀可通过下调NF-κB信号分子的表达及炎性细胞因子的产生,减轻脑出血后脑组织的炎症反应,从而起到脑保护的作用。

Objective To observe the effect of atorvastatin on the expression of NF-κB, TNF-α and IL-1β in the tissues around the hematoma of the rats with intracerebral hemorrhage and explore the protective effect of atorvastatin on the brain of the rats with intracerebral hemorrhage and its possible mechanism. Methods A total of 120 SD rats were randomly divided into the sham group, intracerebral hemorrhage group and treatment group. Both the intracerebral hemorrhage and treatment groups were given the intracerebral injection of autologous blood to establish the models of intracerebral hemorrhage, while the sham group was given the injection with 0.9% sodium chloride at the same site. The treatment group was given intragastric administration of atorvastatin at doses of 10mg/kg 2 hours after operation. The rats were sacrificed and their brain tissues were taken in each group after 12 hours, 1, 2, 3 and 5 days respectively. Immunohistochemistry and Western blot were used to detect the protein expression of TNF-α, IL-1β, and NF-κB in the brain tissue of rats in each group. Results Compared with the sham group, the intracerebral hemorrhage group had significant increase in the expression of NF-κB, TNF-α and IL-1β （P 〈0.05）, and the expression began to increase steadily after 12 hours, reached the peak on the 3rd day, and lasted for 5 days. Compared with the intracerebral hemorrhage group, the expression of NF-κB, TNF-α and IL-1β decreased significantly in the treatment group （P〈0.05）. Conclusion The high expression of NF-κB, TNF-α and IL-1β is involved in the tissues around the hematoma of the rats with intracerebral hemorrhage. Atorvastatin has a protective effect on the brain by reducing the expression of NF-κB signaling molecules, the production of inflammatory cytokines and the inflammatory response~ of brain tissues.