瑞舒伐他汀对局灶性脑缺血再灌注大鼠炎性反应通路的影响

Effects of rosuvastatin on inflammatory response pathway of focal cerebral ischemia reperfusion in rats

目的研究瑞舒伐他汀对局灶性脑缺血再灌注(I/R)大鼠脑组织中炎性反应信号通路的抑制作用。方法按照体重将大鼠随机分为3组:假手术组、模型组和实验组,每组8只。在造模前,实验组用瑞舒伐他汀5 mg·kg^(-1)·d^(-1)连续灌胃10 d。以改良Zea-Longa线栓法制备大鼠右侧大脑中动脉缺血模型。于缺血2 h再灌注24 h后取脑组织,用免疫组织化学法测定Toll样受体4(TLR4)和核转录因子-κB p65(NF-κB p65)阳性细胞表达;用逆转录-聚合酶链反应法和免疫印迹法分别检测脑组织中TLR4和NF-κB p65的基因和蛋白表达情况。结果假手术组、模型组和实验组的TLR4阳性细胞数分别为(12. 69±2. 55),(38. 05±6. 81)和(27. 80±5. 75)个;这3组的NF-κB p65阳性细胞数分别为(14. 64±2. 79),(47. 27±7. 40)和(34. 83±5. 60)个。这3组的TLR4蛋白表达的光密度值分别为0. 28±0. 04,0. 63±0. 09和0. 41±0. 07;这3组的NF-κB p65蛋白表达的光密度值分别为0. 21±0. 04,0. 72±0. 12和0. 36±0. 06。模型组与假手术组比较,上述指标的差异均有统计学意义(均P <0. 05)。实验组与模型组比较,上述指标的差异均有统计学意义(均P <0. 05)。基因结果的趋势与蛋白一致。结论瑞舒伐他汀可通过抑制TLR4/NF-κB通路从而减轻脑I/R后的炎症反应。

Objective To investigate the role of rosuvastatin in inhibiting inflammatory response pathway in rats with focal cerebral ischemia-reperfusion(I/R).Methods Rats were randomly assigned into three groups:sham operation group,model group and experimental group,each group had 8 rats.The rats in the experimental group were lavaged with rosuvastatin 5 mg·kg-1·d-1 for 10 consecutive days before the model setting-up.The middle cerebral artery occlusion I/R model was made by the modified Zea-Longa wire bolt method.At 24 h after reperfusion,the positive cells of Toll like receptor 4(TLR4)and nuclear transcription factor kappa B p65(NF-κB p65)were measured by immunohistochemistry;the levels of the TLR4,NF-κB p65 protein and the TLR4,NF-κB p65 mRNA were measured by Western blotting and reverse transcription PCR,respectively.Results The expressions of TLR4 positive cells in sham group,model group and experimental group were(12.69±2.55)cells,(38.05±6.81)cells and(27.80±5.75)cells,respectively;the expressions of NF-κB p65 positive cells in the three groups were(14.64±2.79)cells,(47.27±7.40)cells and(34.83±5.60)cells,respectively;the expressions of TLR4 protein(optical density,OD)in the three groups were0.28±0.04,0.63±0.09,0.41±0.07;the expressions of NF-κB p65 protein(OD)in the three groups were0.21±0.04,0.72±0.12,0.36±0.06.Comparison between sham operation group and model group showed the difference of the factors were statistically significant(all P<0.05);comparison between model group and experimental group displayed the difference of the factors were statistically significant(all P<0.05).The trend of gene results is consistent with that of protein.Conclusion Rosuvastatin can inhibit TLR4-NF-κB signal transduction pathway and reduce several inflammatory reaction after focal cerebral I/R.