阿托伐他汀对颅脑外伤后小胶质细胞激活的影响

Effects of atorvastatin on the microglia activation after traumatic brain injury

目的观察阿托伐他汀对颅脑损伤(TBI)后小胶质细胞激活的影响。方法将60只C57/BL6小鼠随机分为假手术组、生理盐水组和阿托伐他汀组,各20只。生理盐水组和阿托伐他汀组采用液压打击法制作TBI模型。假手术组不进行液压打击。阿托伐他汀组打击后1 h给予阿托伐他汀(每天1 mg/kg)灌胃,连续7 d。生理盐水组给予等量生理盐水灌胃。采用免疫组化法检测造模后第1、3、7天创伤灶周围小胶质细胞特异性标志物(Iba-1)的数量及第3天基质金属蛋白酶(MMP)-9水平;Western blot检测炎症因子肿瘤坏死因子(TNF)-α水平。结果造模后第1、3、7天,阿托伐他汀组小鼠创伤灶周围Iba-1阳性表达量较生理盐水组均显著降低(80.00±7.44 vs.118.40±6.65,85.60±10.87 vs.189.00±7.51,69.40±5.54 vs.102.40±10.89,P<0.05)。TBI后第3天,阿托伐他汀组MMP-9阳性表达量与生理盐水组相比也显著下降(86.80±8.40 vs.133.80±8.46,P<0.05);Western blot检测发现阿托伐他汀组与生理盐水组相比TNF-α表达下降(0.64±0.01 vs.0.97±0.02,P<0.05)。结论阿托伐他汀能减少小鼠TBI后小胶质细胞的激活,减少炎症因子的表达,起到抗炎作用。

Objective To observe the effects of atorvastatin on the microglia activation after traumatic brain injury（TBI）. Methods Sixty adult male C57/BL6 mice were randomly divided into sham group, atorvastatin group and salinegroup, 20 mice for each group. The atorvastatin group and saline group were given hydraulic combat to establish TBI mousemodel. The shame group underwent the same surgical procedure without being exposed to percussion injury. The atorvastatingroup was treated with atorvastatin（orally, 1 mg/kg）1 h after TBI and for 7 consecutive days. The saline group was given sa-line orally. The expression of microglia（Iba-1＋） at the 1st, 3rd, and 7th day after TBI and matrix metalloproteinase-9（MMP-9） around the lesion at the 3rd day after TBI were detected by immunohistochemical staining. Tumor necrosis factor（TNF）-αwas detected by Western blot assay at the 3rd day after TBI. Results The positive expression of Iba-1＋microglia was signifi-cantly decreased in atorvastatin group than that of saline group at the 1st, 3rd, and 7th day after TBI（80.00±7.44 vs. 118.40±6.65,85.60±10.87 vs. 189.00±7.51,69.40±5.54 vs. 102.40±10.89, P0.05）. The positive expression of MMP-9 was signifi-cantly decreased in atorvastatin group compared with that of saline group at the 3rd day after TBI（86.80±8.40 vs. 133.80±8.46, P0.05）. Results of Western blot assay showed that the positive expression of TNF-α was significantly decreased inastorvastatin group than that of saline group at the 3rd day after TBI（0.64±0.01 vs. 0.97±0.02,P0.05）. Conclusion Ator-vastatin can reduce inflammation factor by influencing the microglia activation after TBI in mice.