瓜子金皂苷己对脑缺血再灌注损伤大鼠NKCC1及炎症因子表达的影响

Effects of Polygalasaponin F on expression of NKCC1 and inflammatory factors in rats injured by cerebral ischemia reperfusion

目的:采用大鼠脑缺血再灌注损伤模型观察瓜子金皂苷己(Polygalasaponin F,PGSF)对脑组织中钠-钾-氯协同转运蛋白1(Na^(+)-K^(+)-2Cl^(-)combined transporter type 1,NKCC1)及炎症因子表达水平的影响。方法:将大鼠按体重随机分为假手术组、模型组、PGSF低剂量组、PGSF中剂量组、PGSF高剂量组,以线栓法制备大脑中动脉阻塞(Middle cerebral artery occlusion,MCAO)模型。除假手术组外其余各组缺血1 h、再灌注24 h。侧脑室立体定位注射给药。以实时荧光定量多聚酶链式反应检测肿瘤坏死因子α(Tumor necrosis factor,TNF-α)、白细胞介素1β(Interleukin-1β,IL-1β)、白细胞介素6(Interleukin-6,IL-6)及NKCC1的mRNA表达情况。结果:脑缺血再灌注处理使病灶组织中TNF-α、IL-1β、IL-6及NKCC1的mRNA表达量均较假手术组明显升高;与模型组相比,PGSF高剂量组、中剂量组及低剂量组TNF-α、IL-1β、IL-6的mRNA表达均明显下调,PGSF高剂量组和中剂量组NKCC1的mRNA表达也显著下调。结论:结合前期研究结果,推测NKCC1可能是PGSF在整体水平影响脑缺血再灌注损伤的重要靶点之一,PGSF还可能通过抑制炎症发挥作用。神经炎症可能直接或间接通过与NKCC1相关机制参与了脑缺血再灌注损伤的病理过程。

Objective:To observe the effects of Polygalasaponin F(PGSF)on the expression of Na^(+)-K^(+)-2Cl^(-)combined transporter type 1(NKCC1)and inflammatory cytokines in brains with cerebral ischemia-reperfusion models of rats.Methods:Rats were randomly divided into the sham group,the model group,the low-dose PGSF group,the medium-dose PGSF group and the high-dose PGSF group,with models of middle cerebral artery occlusion(MCAO)made by using the suture method.All groups except for the sham group were subjected to one-hour MACO and 24-hour reperfusion,with PGSF given by stereotactic injection through the lateral ventricle.RT-PCR was utilized to detect the mRNA expression of TNF-α,IL-1,IL-6 and NKCC1.Results:The mRNA expression levels of TNF-α,IL-1β,IL-6 and NKCC1 in cerebral ischemia-reperfusion group were significantly higher than those in the sham group.Compared with those of the model group,the expressions of TNF-α,IL-1βand IL-6 in all PGSF dose groups were significantly down-regulated,and the mRNA expression of NKCC1 in the high-dose and medium-dose PGSF groups were also down-regulated.Conclusion:Combined with the results of previous studies,it is speculated that NKCC1 may be one of the important targets of PGSF affecting cerebral ischemia-reperfusion injury at the global level,and PGSF may also act on the brain by suppressing inflammation.Neuroinflammation may directly or indirectly participate in the pathological process of cerebral ischemia-reperfusion injury through NKCC1 related mechanisms.