摘要
目的：观察清热、活血中药双黄连、丹参多酚酸盐对动脉粥样硬化大鼠TLR4/My D88/NF-κB信号通路表达的影响。方法：SD大鼠48只,随机分成6组（每组8只）：丹参多酚酸盐（丹多酚）低剂量组、丹多酚高剂量组、双黄连低剂量组、双黄连高剂量组、模型对照组、正常对照组。除了正常组,均注射脂多糖、维生素D3并联合高脂饮食诱导大鼠动脉粥样硬化模型。实验第6周开始,干预组分别用丹参多酚酸盐和双黄连干预治疗6周,第12周实验结束后采用腹主动脉采血休克法处死动物留取标本取材进行相关指标检测。ELISA法检测血清TNF-α、IL-6、P-selection水平;采用酶比色法检测血脂CHOL、TG、HDL-C、LDL-C水平;主动脉标本组织分别行HE染色进行病理形态学观察,分别采用免疫组化法以及western blot法检测主动脉组织TLR4、My D88、NF-κB蛋白表达情况以及水平。结果：（1）4个药物干预组与模型组相比CHOL、TG、LDL-C水平均降低（P〈0.05）;（2）丹多酚高剂量组、双黄连高剂量组与模型组相比TNF-α水平下降（P〈0.05）;丹多酚低剂量组、高剂量组和双黄连高剂量组与模型组相比IL-6水平下降（P〈0.05）;丹多酚低剂量组和高剂量组与模型组相比P-selectin水平下降（P〈0.05）;（3）双黄连高剂量组、丹多酚高剂量组与模型组相比TLR4、My D88的表达均减少（P〈0.05）;（4）4个药物干预组与模型组相比NF-κB表达均下降（P〈0.05）,且两个药物的高剂量组均优于低剂量组（P〈0.05）。结论：双黄连、丹参多酚酸盐均能通过调控动脉粥样硬化大鼠TLR4/My D88/NF-κB信号转导,下调血脂水平,减轻炎症反应,从而抑制动脉粥样硬化进程。
Objective： To observe the effects of heat-clearing,blood-activating drugs on TLR4 signaling pathway in atherosclerosis（ AS） rats. Method： Forty-eight male SD rats were randomly divided into 6 groups： salvianolate high-dose group（ DSG）,salvianolate low-dose group（ DSL）,Shuanghuanglian high-dose group（ SHLG）,Shuanghuanglian low-dose group（ SHLL）,AS model group,normal group. AS model were induced by lipopolysaccharide（ LPS）,high fat diet and vitamin D3 in the first five groups. In the sixth week,we selected Shuanghuanglian and Salvianolate to treat the AS rats in salvianolate and Shuanghuanglian groups. In the twelfth week,the animals were killed by abdominal aortic blood sampling,then we used ELISA method to detect the serum levels of inflammatory factors（ TNF-α,IL-6）. We used enzyme colorimetric method to detect the blood lipid levels（ CHOL,TG,HDL-C,LDL-C）. The pathological structures of thoracic aorta were evaluated by HE staining. The expressions of TLR4,My D88,and NF-κB were detected with Immunohistochemical Technique and Western Blot. Results：（ 1） Compared with AS model group,the four intervention groups＇ CHOL,TG and LDL-C decreased obviously（ P 0. 05） and the HDL-C increased（ P 0. 05）.（ 2） Compared with AS model group,DSG and SHLG＇s TNF-α decreased（ P 0. 05）. DSG,DSL and SHLG＇s IL-6 decreased（ P 0. 05）. DSL and DSG＇s P-selection decreased（ P 0. 05）.（ 3） Compared with AS model group,DSG and SHLG＇s TLR4 and My D88 decreased（ P 0. 05）.（ 4） Compared with AS model group,the expression of NF-kappa B was decreased in all Salvianolate and Shuanghuanglian groups（ P 0. 05） and the high-dose group＇s was better than that of the low-dose group（ P 0. 05）. Conclusion： Shuanghuanglian and Salvianolate may supress the atherosclerosis in SD rats through TLR4/My D88/NF-κβ signaling pathway.
出处
《中华中医药学刊》
CAS
北大核心
2018年第3期576-580,I0010-I0013,共9页
Chinese Archives of Traditional Chinese Medicine
基金
国家自然科学基金项目(81673923)
关键词
TLR4信号
清热活血中药
动脉粥样硬化
TLR4 signaling pathway
heat - clearing, blood - activating traditional Chinese drug
atherosclerosis
