Mechanism of Renshentang in Treatment of Atherosclerosis Based on Autophagic Effect of TRPV1 on Arterial Smooth Muscle

QI Yujie; HE Zhanzhan; YANG Zhen; TAO Xuguang; CHU Ce; YUAN Yulu; CHEN Xiangyun; DING Wei; ZHAO Peizhang; ZHAO Hongxia; WANG Wenlai

doi:10.13422/j.cnki.syfjx.20230903

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Mechanism of Renshentang in Treatment of Atherosclerosis Based on Autophagic Effect of TRPV1 on Arterial Smooth Muscle

更新时间：2023-05-16

- Mechanism of Renshentang in Treatment of Atherosclerosis Based on Autophagic Effect of TRPV1 on Arterial Smooth Muscle
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 12, Pages: 55-62(2023)
- 作者机构：
  
  1.中国中医科学院中医基础理论研究所，北京 100700
  2.北京中医药大学，北京 100029
  3.四川大学华西临床医学院，成都 610041
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20230903
  CLC： R2-0;R22;R285.5;R289;R33
- Published：20 June 2023，
  
  Published Online：06 April 2023，
  
  Received：15 March 2023，
- 稿件说明：
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亓玉婕,何湛湛,杨桢等.基于TRPV1对动脉血管平滑肌的自噬作用探讨人参汤治疗AS的作用机制[J].中国实验方剂学杂志,2023,29(12):55-62.

QI Yujie,HE Zhanzhan,YANG Zhen,et al.Mechanism of Renshentang in Treatment of Atherosclerosis Based on Autophagic Effect of TRPV1 on Arterial Smooth Muscle[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(12):55-62.
亓玉婕,何湛湛,杨桢等.基于TRPV1对动脉血管平滑肌的自噬作用探讨人参汤治疗AS的作用机制[J].中国实验方剂学杂志,2023,29(12):55-62. DOI： 10.13422/j.cnki.syfjx.20230903.

QI Yujie,HE Zhanzhan,YANG Zhen,et al.Mechanism of Renshentang in Treatment of Atherosclerosis Based on Autophagic Effect of TRPV1 on Arterial Smooth Muscle[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(12):55-62. DOI： 10.13422/j.cnki.syfjx.20230903.

摘要

目的

基于香草酸受体亚型1（TRPV1）对动脉血管平滑肌的自噬作用探讨《金匮要略》人参汤治疗动脉粥样硬化（AS）的作用机制。

方法

SPF级8周龄雄性C57BL/6J小鼠14只作为正常组，8周龄载脂蛋白E基因敲除（ApoE

-/-

）小鼠70只作为模型组。模型组采用高脂饲料喂食8周制备AS小鼠模型，随后随机分为模型组、人参汤低、中、高剂量（2.715、5.43、10.68 g·kg

-1

·d

-1

）组和辛伐他汀（0.02 g·kg

-1

·d

-1

）组，连续给药8周。8周后，取血清，采用检测试剂盒测定血清总胆固醇（CHO）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）水平，观察小鼠血脂水平的变化；取主动脉，采用苏木素-伊红（HE）染色观察主动脉根部整体的病理情况，采用油红O染色检测主动脉斑块内脂质沉积情况，并计算主动脉根部面积占管腔面积百分比；采用蛋白免疫印迹法（Western blot）检测小鼠主动脉组织中TRPV1、腺苷酸活化蛋白激酶（AMPK）、磷酸化腺苷酸活化蛋白激酶（p-AMPK）及自噬效应蛋白-1（Beclin-1）、微管相关蛋白1轻链3Ⅱ（LC3Ⅱ）、微管相关蛋白1轻链Ⅰ（LC3Ⅰ）的表达情况。

结果

与正常组比较，模型组小鼠血清中CHO、TG、LDL-C水平显著升高，HDL-C水平显著降低，主动脉根部斑块面积显著增多（

0.01）；与模型组比较，人参汤各剂量组可明显降低AS模型小鼠血清中CHO、TG、LDL-C水平（

0.05，

0.01），人参汤低、中剂量组最为显著（

0.01）。与正常组比较，辛伐他汀组、人参汤低、中、高剂量组均能明显减少主动脉根部斑块面积（

0.05，

0.01），其中人参汤高剂量组效果减轻斑块效果最为显著（

0.01）。与正常组比较，模型组小鼠的TRPV1、p-AMPK/AMPK、Beclin-1、LC3Ⅱ/LC3Ⅰ的相对表达量明显降低（

0.05，

0.01）；与模型组比较，人参汤中、高剂量组TRPV1、p-AMPK/AMPK、Beclin-1、LC3Ⅱ/LC3Ⅰ的相对表达量均明显升高（

0.05，

0.01）。

结论

《金匮要略》人参汤具有抗AS作用，其作用机制可能是通过调节TRPV1的表达上升，进而恢复了由AMPK介导的自噬水平实现的。

Abstract

Objective

To investigate the mechanism of Renshentang， recorded

Synopsis of Golden Chamber

， in the treatment of atherosclerosis （AS） based on the autophagic effect of transient receptor potential vanilloid subtype 1 （TRPV1） on arterial smooth muscle.

Method

Fourteen SPF-grade 8-week-old male C57BL/6J mice were assigned to the normal group and 70 8-week-old apolipoprotein E knockout （ApoE

-/-

） mice were assigned to the experimental group. The AS model was induced by a high-fat diet in the mice in the experimental group for eight weeks. The model mice were then randomly divided into model group， low-， medium-， and high-dose Renshentang groups （2.715， 5.43， and 10.68 g·kg

-1

·d

-1

）， and simvastatin group （0.02 g·kg

-1

·d

-1

）. Drug treatment lasted eight weeks. Serum was taken and serum total cholesterol （CHO）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） levels were measured by assay kits to observe the changes in lipid levels in mice. The aorta was stained with hematoxylin-eosin （HE） to observe the overall pathology of the aortic root and oil red O staining was used to detect the lipid deposition in the aortic plaque and calculate the percentage of the aortic root area to the lumen area. The protein expression of TRPV1， adenylate-activated protein kinase （AMPK）， phosphorylated AMPK （p-AMPK）， autophagy effector-1 （Beclin-1）， and microtubule-associated protein 1 light chain 3 （LC3Ⅱ） in mouse aortic tissues was determined by Western blot.

Result

Compared with the normal group， the model group showed increased serum CHO， TG， and LDL-C levels， decreased HDL-C， and increased aortic root plaque area （

0.01）. Compared with the model group， the Renshentang groups showed decreased levels of CHO， TG， and LDL-C in serum （

0.05，

0.01）， especially in the low- and medium-dose Renshentang groups （

0.01）. Compared with the normal group， the simvastatin group and the Renshentang groups showed reduced aortic root plaque area （

0.05）， especially in the high-dose Renshentang group （

0.01）. Compared with the normal group， the model group showed decreased relative expression levels of TRPV1， p-AMPK/AMPK， Beclin-1， and LC3Ⅱ/LC3Ⅰ（

0.05，

0.01）. Compared with the model group， the medium- and high-dose Renshentang groups showed increased relative expression levels of TRPV1， p-AMPK/AMPK， Beclin-1， and LC3Ⅱ/LC3Ⅰ（

0.05，

0.01）.

Conclusion

The anti-AS effect of Renshentang recorded

Synopsis of Golden Chamber

may be achieved by up-regulating TRPV1 expression to restore the level of autophagy mediated by AMPK.

关键词

《金匮要略》人参汤动脉粥样硬化香草酸受体亚型1自噬载脂蛋白E基因敲除小鼠

Keywords

Renshentang recorded in Synopsis of Golden Chamberatherosclerosis （AS）transient receptor potential vanilloid subtype 1 （TRPV1）autophagyapolipoprotein E knockout （ApoE-/-） mice

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