摘要
目的 探究丁苯酞通过调节Toll样受体4(TLR4)/核转录因子-κB(NF-κB)通路对急性脑梗死(ACI)大鼠神经损伤的保护作用.方法 SD大鼠随机分为假手术组、模型组、低、中、高剂量实验组,除假手术组外均建立ACI体内模型.造模2d后,低、中、高剂量实验组灌胃给予20、40和80 mg·kg-1 丁苯酞,qd,假手术组、模型组灌胃等量0.9％NaCl,均灌胃7d.统计各组大鼠神经功能评分、双侧贴纸去除时间、平衡木过杆评分、脑含水量和脑梗死体积,酶联免疫吸附试验法(ELISA)检测血清和海马组织轴突生长抑制因子A(Nogo-A)、血清炎性因子表达,用蛋白质印迹法检测TLR4/NF-κB通路蛋白表达.结果 假手术组、模型组和低、中、高剂量实验组的神经功能评分分别为0、(3.55±0.52)、(2.55±0.52)、(1.82±0.60)和(0.91±0.30)分,海马组织Nogo-A 表达量分别为(0.93±0.23)、(6.32±0.53)、(5.10±0.55)、(3.54±0.57)和(1.58±0.30)ng·L-1,血清 Nogo-A 表达量分别为(0.49±0.12)、(5.09±0.82)、(3.83±0.54)、(2.23±0.64)和(1.13±0.25)ng·L-1,TLR4 蛋白相对表达水平分别 为 0.44±0.05、1.23±0.14、0.93±0.07、0.75±0.06 和0.55±0.07,p-p65 NF-κB蛋白相对表达水平分别为0.32±0.05、0.82±0.06、0.68±0.08、0.57±0.07 和 0.44±0.05.假手术组的上述指标与模型组比较,在统计学上差异均有统计学意义(均P＜0.05);模型组的上述指标与低、中、高剂量实验组比较,在统计学上差异均有统计学意义(均P＜0.05).结论 丁苯酞可通过调节TLR4/NF-κB通路改善ACI大鼠神经功能,并减轻炎症损伤,从而发挥神经保护作用.
Abstract
Objective To investigate the protective effect of butyrolphthalein on nerve injury in rats with acute cerebral infarction(ACI)by regulating Toll-like receptor 4(TLR4)/nuclear transcription factor-κB(NF-κB)pathway.Methods SD rats were randomly divided into model group and experimental-L,-M,-H groups;ACI models were established in vivo except sham operation group.The experimental-L,-M,-H groups were given 20,40,80 mg·kg-1 butylphthalide,qd,for 7 days;the sham operation group and the model group were given the same amount of 0.9％NaCl,for 7 days.Neural function score,bilateral sticker removal time,balance beam crossing score,cerebral water content and cerebral infarction volume of rats in each group were measured.The expression of axonal growth inhibitory factor A(Nogo-A)and serum inflammatory factor in hippocampus were detected by enzyme-linked immunosorbent assay(ELISA).The expression of TLR4/NF-κB pathway related proteins was detected by Western blot.Results The neural function scores of sham operation group,model group,and experimental-L,-M,-H groups were 0,3.55±0.52,2.55±0.52,1.82±0.60,0.91±0.30,respectively;the Nogo-A in hippocampus were(0.93±0.23),(6.32±0.53),(5.10±0.55),(3.54±0.57),(1.58±0.30)ng·L-1,respectively;serum Nogo-A were(0.49±0.12),(5.09±0.82),(3.83±0.54),(2.23±0.64),(1.13±0.25)ng·L-1,respectively;TLR4 protein expression were 0.44±0.05,1.23±0.14,0.93±0.07,0.75±0.06,0.55±0.07,respectively;the expressions of p-p65 NF-κB protein were 0.32±0.05,0.82±0.06,0.68±0.08,0.57±0.07,0.44±0.05,respectively.There were statistically significant differences between sham operation group and model group(all P＜0.05).There were significant differences in the above indexes between the model group and the experimental-L,-M,-H groups(P＜0.05).Conclusion Butylphthalein can play a neuroprotective role in ACI rats by regulating TLR4/NF-κB pathway to improve nerve function and reduce inflammatory damage.
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