Cx43基因敲除减轻LPS腹腔注射后胶质细胞的活化和脑内炎症反应

Connexin43 knock-out alleviated the brain inflammation and glia activation induced by peripheral LPS injection

目的考察缝隙连接蛋白43(connexin43,Cx43)基因敲除对脂多糖(lipopolysacchiride,LPS)腹腔注射后胶质细胞的活化和脑内炎症反应的影响。方法采用腹腔LPS注射方法制作外周免疫激活小胶质细胞模型,实验动物共分为4组。Cx43基因敲除小鼠LPS腹腔注射组(Cx43KO-LPS组),Cx43基因敲除小鼠生理盐水对照组(Cx43 KO-NS组),野生小鼠LPS腹腔注射组(WT-LPS组)和野生小鼠生理盐水对照组(WT-NS组)。通过免疫荧光染色的方法观察小胶质细胞(Iba1)和星形胶质细胞(GFAP),通过Western blot方法考察脑内炎症介质IL-1β的变化。结果免疫荧光染色结果提示,Iba1和GFAP的荧光光密度在Cx43 KO-LPS组显著高于Cx43 KO-NS组,WT-LPS组显著高于WT-NS组,WT-LPS组显著高于Cx43KO-LPS组。IL-lβ水平在腹腔注射LPS的2组均高于2个生理盐水对照组,但在WT-LPS组具有最高的表达。结论 Cx43基因敲除能够减轻LPS腹腔注射后脑内炎症介质IL-1β的表达升高,减轻小胶质细胞和星形胶质细胞的活化。

Objective To study the effect of connexin43（Cx43） on brain inflammation and glia activation after peripheral lipopolysacchiride（LPS） injection.Methods The peripheral LPS injection was used to induce brain inflammation and normal saline（NS） injection was used as control in connexin43 knock-out（Cx43KO） and wild（WT）mice.The animals were divided into 4 groups：Cx43KO-NS group,Cx43KO-LPS group,the WT-NS group and WT-LPS group.The immunohistochemistry of Iba1 and GFAP was performed to observe glia activation.The brain inflammation was detected by measurement of IL-1βexpression.Results The fluorescence density of Iba1 and GFAP in the cortex was significantly stronger in Cx43KO-LPS group than in Cx43KO-NS group,stronger in WT-LPS group than in WT-NS group,and much stronger in WT-LPS group than in Cx43KO-LPS significantly.The IL-1β expression level was increased in both Cx43KO-LPS group and WT-LPS group compared to NS groups,but higher in WT-LPS group than in Cx43KO-LPS.Conclusion Connexin43 knock out inhibited the increase of IL-1β expression and alleviated glia activation after LPS injection.