辛伐他汀对脑出血大鼠继发性炎症损伤的防治作用及作用机制研究

Preventive and Therapeutic Effect and Action Bechanism of Simvastatin on Secondary Inflammatory Injury in Rats with Cerebral Hemorrhage

目的:观察辛伐他汀对大鼠脑出血后继发性炎症损伤的预防和治疗作用,并探讨作用机制。方法:选取9～12周龄的健康雄性SD大鼠60只为研究对象,随机分为对照组、模型组与辛伐他汀组,各20只。模型组和辛伐他汀组大鼠建立脑出血模型,建模成功后辛伐他汀组给予辛伐他汀[3 mg/(kg·d),qd]灌胃,模型组和对照组用等体积的生理盐水灌胃。比较三组神经功能行为学评分(NDS)、未损伤的神经元数目及脑组织中核因子κB(NF-κB)、Toll样受体4(TLR4)和白介素(IL)-1β的阳性细胞数。结果:建模后所有时间点,辛伐他汀组与模型组NDS均低于对照组,辛伐他汀组NDS均高于模型组,差异有统计学意义(P <0.05);建模后12 h、24 h、48 h、72 h与7 d辛伐他汀组未受损神经元数目均高于模型组,差异有统计学意义(P <0.05);建模后7 d,辛伐他汀组和模型组NF-κB、TLR4、IL-1β阳性细胞数目均高于对照组,辛伐他汀组NF-κB、TLR4、IL-1β阳性细胞数目均低于模型组,差异有统计学意义(P <0.05)。结论:辛伐他汀能抑制脑出血大鼠病变周围脑组织中NF-κB、TLR4和IL-1β的表达,可能通过下调TLR4介导的NF-κB通路,进而抑制IL-1β,减轻炎症反应,减少脑组织的继发性炎症损伤。

Objective:To observe the preventive and therapeutic effect of simvastatin on secondary inflammatory injury after cerebral hemorrhage in rats,and to explore its action mechanism.Methods:60 healthy male Sprague-Dawley rats aged 9~12 weeks were selected as subjects investigated and randomly divided into a control group,a model group and a simvastatin group,20 rats each.The cerebral hemorrhage models were established in the rats of the model group and the simvastatin group.After successful modeling,the rats in the simvastatin group were given simvastatin[3 mg/(kg·d),qd]intragastrically,and the rats in the model group and the control group were given the same volume of saline intragastrically.The neurological function deficit scale(NDS),the number of uninjured neurons and the number of nuclear factor kappa B(NF-κB),Toll-like receptor 4(TLR4)and interleukin(IL)-1βpositive cells in brain tissues were compared between the three groups.Results:At all time points after modeling,the NDS in the simvastatin group and the model group was lower than that in the control group,and the NDS in the simvastatin group was higher than that in the model group,with statistically significant differences(P<0.05).The number of uninjured neurons at 12 h,24 h,48 h,72 h and 7 days after modeling in the simvastatin group was higher than that in the model group(P<0.05).On the 7th day after modeling,the number of NF-κB,TLR4 and IL-1βpositive cells in the simvastatin group and the model group was higher than that in the control group,and the number of NF-κB,TLR4 and IL-1βpositive cells in the simvastatin group was lower than that in the model group,with statistically significant differences(P<0.05).Conclusion:Simvastatin can inhibit the expressions of NF-κB,TLR4 and IL-1βin brain tissue around lesions in rats with cerebral hemorrhage possibly by down-regulating TLR4-mediated NF-κB pathway,thereby inhibiting IL-1β,alleviating inflammation and reducing secondary inflammatory injury in brain tissues.