芪蛭通脉颗粒对冠状动脉粥样硬化模型大鼠的干预作用机制研究

Study on mechanism of Qizhi Tongmai granule for coronary atherosclerosis model rats

目的观察芪蛭通脉颗粒对冠状动脉粥样硬化模型大鼠的干预作用机制。方法将60只Wistar大鼠随机分为空白对照组、模型组、阿托伐他汀钙组及芪蛭通脉低、中、高剂量组,每组10只。除空白对照组外,其余各组均进行冠状动脉粥样硬化造模。造模成功后,芪蛭通脉低、中、高剂量组分别按6.5、13、26 g/(kg·d)给予芪蛭通脉水溶液灌胃,阿托伐他汀钙组按13 mg/(kg·d)给予阿托伐他汀钙水溶液灌胃,空白对照组按5 mL/kg给予蒸馏水灌胃,各组均连续灌胃4周。比较各组灌胃后血清白细胞介素6(IL-6)、IL-8、IL-10水平及冠状动脉组织Toll样受体4(TLR4)、核因子κB(NF-κB)蛋白表达情况。结果与空白对照组比较,模型组血清IL-6、IL-8水平均升高(P<0.05),IL-10水平降低(P<0.05);与模型组比较,芪蛭通脉中、高剂量组血清IL-6、IL-8水平均降低(P<0.05),芪蛭通脉高剂量组IL-10水平升高(P<0.05),阿托伐他汀钙组、芪蛭通脉低剂量组IL-6、IL-8、IL-10水平及芪蛭通脉中剂量组IL-10水平与模型组比较差异均无统计学意义(P>0.05);芪蛭通脉3个剂量组组间比较,芪蛭通脉高剂量组血清IL-6、IL-8水平均低于芪蛭通脉低剂量组(P<0.05)、IL-10水平高于芪蛭通脉低剂量组(P<0.05),IL-8水平低于芪蛭通脉中剂量组(P<0.05),芪蛭通脉中剂量组IL-6、IL-8水平均低于芪蛭通脉低剂量组(P<0.05)。与空白对照组比较,模型组冠状动脉组织TLR4、NF-κB相对表达升高(P<0.05);与模型组比较,芪蛭通脉低、中、高剂量组冠状动脉组织TLR4、NF-κB相对表达均降低(P<0.05),阿托伐他汀钙组仅NF-κB相对表达降低(P<0.05),阿托伐他汀钙组TLR4相对表达与模型组比较差异无统计学意义(P>0.05);芪蛭通脉3个剂量组组间比较,芪蛭通脉低、中、高剂量组冠状动脉组织TLR4、NF-κB相对表达组间比较差异均无统计学意义(P>0.05)。结论芪蛭通脉颗粒对冠状动脉粥样硬化大鼠治疗作用确切,其作用机制可能与调控TLR4/NF-κB信号通路,抑制炎性反应有关,但其有效剂量及明确的量效关系有待进一步深入研究。

Objective To observe the intervention mechanism of Qizhi Tongmai granule for coronary atherosclerosis(CA)model rats.Methods Totally 60 Wistar rats were randomly assigned into 10 each with blank control group,model group,atorvastatin calcium(ATC)group and Qizhi Tongmai granule low-,medium-and high-dose groups.Apart from the blank control group,the CA model of the other groups was established.After successful molding,Qizhi Tongmai granule low-,medium-and high-dose groups were separately gavaged with Qizhi Tongmai granules of 6.5,13 and 26 g·kg^(-1)·d^(-1).ATC group and blank control group were treated with 13 mg·kg^(-1)·d^(-1)ATC and 5 mL·kg^(-1)distilled water by gavage,respectively.Each group was given gavage for 4 weeks.The aim was to compare interleukine-6(IL-6),IL-8,IL^(-1)0,protein expression of Toll-like receptor 4(TLR4)/nuclear factor-kappaB(NF-κB)levels.Results Increased IL-6,IL-8,and decreased IL^(-1)0 were detected in model group than those in blank control group(all P<0.05).In comparison of Qizhi Tongmai granule groups and model group,Qizhi Tongmai granule medium-and high-dose groups displayed decreased IL-6,IL-8,and Qizhi Tongmai granule high-group displayed increased IL^(-1)0(all P<0.05).The levels of IL-6,IL-8,IL^(-1)0 in ATC group and Qizhi Tongmai granule low-group,and IL^(-1)0 in Qizhi Tongmai granule medium-group were not significantly different from those in the model group(P>0.05).The levels of IL-6,IL-8 in the comparison of Qizhi Tongmai granule groups,Qizhi Tongmai granule high-group was lower than Qizhi Tongmai granule medium-group,and Qizhi Tongmai granule medium-group was lower than Qizhi Tongmai granule low-group(all P<0.05).IL^(-1)0 was increased in Qizhi Tongmai granule high-group compared with Qizhi Tongmai granule low-,medium-group(P<0.05).TLR4 and NF-κB were increased in model group than in blank control group(P<0.05);reduced TLR4 and NF-κB in Qizhi Tongmai granule groups,and reduced NF-κB in ATC group were found compared with model group(all P<0.05).The difference was not statistically significant in TLR4 between ATC group and model group(P>0.05).None of the TLR4 and NF-κB differed significantly among the three Qizhi Tongmai granule groups(P>0.05).Conclusion For CA rats,Qizhi Tongmai granule has a definite therapeutic effect,and its mechanism is correlated with the regulation of TLR4/NF-κB signaling pathway and inhibition of inflammatory response.Its effective dose and definite dose-effect relationship need to be further studied.