天香丹对动脉粥样硬化模型小鼠TLR4/NF-κB信号通路的影响

Effects of Tianxiang Dan on TLR4/NF-κB Signaling Pathway in Atherosclerosis Model Mice

目的通过研究天香丹对动脉粥样硬化(AS)模型小鼠Toll样受体-4(TLR4)/核因子-κB(NF-κB)信号通路及相关炎症因子的影响,探讨天香丹防治AS的可能机制。方法选取8周龄ApoE-/-小鼠30只予以高脂饲料喂养12周,造模成功后随机分为模型组、他汀组、天香丹组,每组10只;另取10只C57BL/6J小鼠予以普通饲料喂养作为空白对照组。他汀组、天香丹组分别以相应药液3 mg/kg、2.7 g/kg灌胃干预,空白组、模型组以0.5 mL蒸馏水灌胃,每日1次,连续12周。取小鼠血清用于检测血脂水平及TLR4、NF-κB、肿瘤坏死因子-α(TNF-α)含量,取主动脉用于观察主动脉病理变化情况。结果1)HE染色结果显示:他汀组、天香丹组病理改变较模型组轻,斑块稳定性提高,模型组主动脉斑块面积(PA)与管腔面积(LA)比值显著大于空白组(P<0.01),他汀组、天香丹组PA/LA比值则小于模型组(P<0.01)。2)血脂检测结果显示:较空白组,模型组三酰甘油(TAG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)明显升高,高密度脂蛋白胆固醇(HDL-C)明显降低(P<0.01);与模型组比较,他汀组、天香丹组TAG及TC降低明显(P<0.01),天香丹组HDL-C升高(P<0.01)、LDL-C降低(P<0.01)。3)ELISA结果显示:模型组血清中TLR4、NF-κB、TNF-α含量均高于空白组(P<0.01),他汀组、天香丹组血清中TLR4、NF-κB、TNF-α含量均低于模型组(P<0.01)。结论天香丹具有防治AS的作用,其机制可能与调控TLR4/NF-κB信号通路、抑制炎症反应有关。

Objective:To observe the effect of Tianxiang Dan on the toll-like receptor-4(TLR4)/nuclear factor-κB(NF-κB)signaling pathway and related inflammatory factors in atherosclerosis(AS)model mice,and to explore the possible mechanism of prevention and treatment of AS by Tianxiang Dan.Methods:308-week-old ApoE-/-mice were selected and fed with high-fat diet for 12 weeks.After successful modeling,they were randomly divided into the model group,statin group,and Tianxiang Dan group,with 10 mice in each group;another 10C57BL/6J mice were fed with normal feed as the control group.The statin group and Tianxiang Dan group were given the corresponding drug with 3 mg/kg,2.7 g/kg,and the blank group and model group were intragastrically administered with 0.5 mL of distilled water,once a day,for 12 weeks.The serum of the mice was used to detect the blood lipid level and the content of TLR4,NF-κB and TNF-α,and the aorta was used to observe the pathological changes of the aorta.Results:HE staining results showed that the pathological changes in the statin group and Tianxiang Dan group were lighter than those in the model group,and the plaque stability was improved.The ratio of aortic plaque area(PA)to lumen area(LA)in the model group was significantly greater than that in the blank group(P<0.01),the ratio of PA/LA in the statin group and Tianxiang Dan group was lower than that in the model group(P<0.01).The blood lipid detection results showed that compared with the blank group,the model group had significantly higher TAG,TC,LDL-C,and significantly lower HDL-C(P<0.01);compared with the model group,TAG and TC in the statin group and Tianxiang Dan group decreased significantly(P<0.01),while the HDL-C increased(P<0.01)and LDL-C decreased(P<0.01)in the Tianxiang Dan group.ELISA results showed that the serum levels of TLR4,NF-κB and TNF-αin the model group were higher than those in the blank group(P<0.01),and the serum levels of TLR4,NF-κB and TNF-αin the statin group and Tianxiang Dan group were lower than those in the model group(P<0.01).Conclusion:Tianxiang Dan has the effect of preventing and treating AS,and its mechanism may be related to the regulation of TLR4/NF-κB signaling pathway and the inhibition of inflammatory response.