心痛泰颗粒预防性给药对动脉粥样硬化兔主动脉TLR4、p38 MAPK蛋白及mRNA表达的影响

Effect of Preventive Administration of Xintongtai Granule on Protein and mRNA Expression of TLR4 and p38 MAPK in Aorta Tissue of Atherosclerosis Rabbits

目的探讨心痛泰颗粒预防性给药对动脉粥样硬化(AS)兔Toll样受体4(TLR4)、p38丝裂原活化蛋白激酶(p38 MAPK)蛋白及mRNA表达的影响。方法120只兔随机分为空白组(K),模型组(M),心痛泰颗粒高(G)、中(Z)、低(D)剂量组和瑞舒伐他汀组(R),每组20只。K组喂养基础饲料,其余各组均采用高脂饲料喂养联合免疫损伤复制AS模型。在造模同时,G、Z、D、R组每天给药剂量分别为1.44、0.72、0.36 g/kg及0.55 mg/kg,K组与M组灌服同等体积的生理盐水,共8周。观察主动脉组织的病理形态学变化,并检测血脂含量及主动脉TLR4、p38 MAPK蛋白及mRNA的表达量。结果M组内膜壁明显增厚,有大量的泡沫细胞聚集及炎性细胞浸润,中膜细胞排列疏松紊乱,各给药组均有不同程度的减轻,以Z、G、R组较为明显。与K组比较,M组血TC、TG、LDL含量及主动脉TLR4、p38 MAPK蛋白及mRNA的表达升高(P<0.01)。与M组比较,D组血TG含量及主动脉p38 MAPK mRNA表达明显降低(P<0.05),Z组、G组及R组血TC、TG、LDL含量及主动脉TLR4 mRNA、p38 MAPK蛋白及mRNA的表达降低(P<0.05,P<0.01)。结论心痛泰颗粒通过下调TLR4、p38 MAPK蛋白及mRNA表达,调节血脂代谢,延缓动脉粥样硬化。

Objective To explore the effect of preventive administration of Xintongtai Granule(XG)on mR-NA and protein expression level of toll like receptor 4(TLR4)and p38 mitogen-activated protein kinase(p38 MAPK)in aorta tissue of atherosclerosis(AS)rabbits.Methods Totally 120 rabbits were randomly divided into the blank control group(K),the model group(M),the low dose XG group(D,0.36 g/kg),the middle dose XG group(Z,0.72 g/kg),the high dose XG group(G,1.44 g/kg),and the rosuvastatin group(R,0.55 mg/kg),20 in each group.Except those in the K group were fed with basic diet,all other rabbits were fed with high fat diet combined with immune injury to establish AS model.At the same time,XG groups and R group were given drug intervention,while K and M group were given the equal volume of normal saline for 8 weeks.After treatment,pathomorphological changes of aorta tissue were observed.Lipid fat content,mRNA and protein expression levels of TLR4 and p38 MAPK were detected.Results The intima of aorta with a large number of foam cell aggregation and inflammatory cell infil-tration were thickened,and tunica media aortae were loose and disordered.Compared with the M group,all lesions were somewhat ameliorated in all medicated groups,especially in the Z,G and R group.Compared with the K group,the contents of TC,TG and LDL,mRNA and protein expression levels of TLR4 and p38 MAPK in aorta tissue increased significantly in the M group(P<0.01).Compared with the M group,the contents of TG and mRNA ex-pression level of p38 MAPK decreased obviously in the D group(P<0.05),the contents of TC,TG and LDL,mR-NA and protein expression level of TLR4 and p38 MAPK in aorta tissue decreased obviously in the Z group,G group and R group(P<0.05,P<0.01).Conclusion XG could delay AS possibly through down-regulating mRNA and protein expression levels of p38 MAPK and TLR4 in aorta tissue,and regulating blood lipid metabolism.