醒脑静调节CREB/PGC-1α信号通路对创伤性脑损伤大鼠神经炎症的影响

Effects of Xingnaojing on Neuroinflammation in Rats with Traumatic Brain Injury by Regulating CREB/PGC-1αSignal Pathway

目的分析醒脑静调节cAMP反应元件结合蛋白(CREB)/过氧化物酶体增殖物激活受体γ辅激活因子1-α(PGC-1α)通路对创伤性脑损伤(TBI)大鼠神经炎症的影响。方法将75只SD大鼠分为对照组、模型组、醒脑静低剂量组(0.52mL/100g)、醒脑静高剂量组(1.04mL/100g)、醒脑静高剂量组+666-15(CREB抑制剂)组(10mg/kg),每组15只,除对照组外均构建创伤性脑损伤模型,计算大鼠神经损伤严重程度评分(NSS),干湿比重法测定大鼠脑含水量,TUNEL法测定大鼠神经细胞凋亡情况,ELISA法测定大鼠脑组织中肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)、白介素6(IL-6)水平,Western blot法测定大鼠CREB/PGC-1α通路蛋白表达。结果与对照组相比,模型组大鼠NSS评分、脑含水量、神经细胞凋亡率、脑组织TNF-α、IL-1β、IL-6水平、p-CREB/CREB、PGC-1α蛋白表达升高(P<0.05);与模型组相比,醒脑静低剂量组、醒脑静高剂量组大鼠NSS评分、脑含水量、神经细胞凋亡率、脑组织TNF-α、IL-1β、IL-6水平降低,脑组织p-CREB/CREB、PGC-1α蛋白表达升高(P<0.05);与醒脑静高剂量组相比,醒脑静高剂量+666-15组大鼠NSS评分、脑含水量、神经细胞凋亡率、脑组织TNF-α、IL-1β、IL-6水平升高,脑组织p-CREB/CREB、PGC-1α蛋白表达降低(P<0.05)。结论醒脑静可能通过激活CREB/PGC-1α通路抑制TBI大鼠神经炎症。

Objective To analyze the effect of Xingnaojing on neuroinflammation in rats with traumatic brain injury(TBI)by regulating cAMP response element binding protein(CREB)/peroxisome proliferator activated receptorγcoactivator 1α(PGC-1α)pathway.Methods 75 SD rats were divided into the control group,model group,low-dose Xingnaojing group(0.52mL/100g),high-dose Xingnaojing group(1.04mL/100g),and high-dose Xingnaojing group+666-15(CREB inhibitor)group(10mg/kg),with 15 rats in each group.Traumatic brain injury models were established in all groups except for the control group.The nerve injury severity score(NSS)of all rats was calculated,while the brain water content was measured by dry-wet method.TUNEL method was used to measure the apoptosis of nerve cells in rats.Levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)in brain tissue of rats were measured by ELISA.The expression of CREB/PGC-1αpathway protein was determined by western blot.Results Compared with the control group,NSS score,brain water content,neuronal apoptosis rate,TNF-α,IL-1β,and IL-6 levels in brain tissue,p-CREB/CREB,PGC-1αprotein expression in the model group increased(P<0.05);Compared with the model group,the NSS score,brain water content,neuronal apoptosis rate,TNF-α,IL-1βand IL-6 levels in brain tissue of rats in low-dose and high-dose Xingnaojing groups decreased,while the expression of p-CREB/CREB and PGC-1αproteins in brain tissue increased(P<0.05);Compared with the high dose Xingnaojing group,NSS score,brain water content,neuronal apoptosis rate,TNF-α,IL-1βand IL-6 levels in brain tissue of rats in the high dose Xingnaojing+666-15 group increased,while the expression of p-CREB/CREB and PGC-1αproteins in brain tissue decreased(P<0.05).Conclusion The current study suggests that Xingnaojing may inhibit neuroinflammation in TBI rats by activating CREB/PGC-1αpathway.