Anti-inflammation and Regulation of HIF-1<italic style="font-style: italic">α</italic>/VEGF of 3 Kinds of Borneolum in Prevention and Treatment of AMI Model Rats

Liying WANG; Jian WANG; Yamei FAN; Jiajun WANG; Yin FU; Xianjuan YANG; Daoyin GONG

doi:10.13422/j.cnki.syfjx.20221009

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Anti-inflammation and Regulation of HIF-1α/VEGF of 3 Kinds of Borneolum in Prevention and Treatment of AMI Model Rats

更新时间：2022-08-30

- Anti-inflammation and Regulation of HIF-1α/VEGF of 3 Kinds of Borneolum in Prevention and Treatment of AMI Model Rats
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 28, Issue 19, Pages: 61-72(2022)
- 作者机构：
  
  1.成都中医药大学药学院，成都 611137
  2.成都中医药大学附属医院，成都 610075
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20221009
  CLC： R2-0;R22;R285.5;R284;R33
- Published：05 October 2022，
  
  Published Online：28 March 2022，
  
  Received：11 January 2022，
- 稿件说明：
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王立映,王建,樊亚梅等.3种冰片防治AMI模型大鼠的抗炎及调控HIF-1α/VEGF[J].中国实验方剂学杂志,2022,28(19):61-72.

WANG Liying,WANG Jian,FAN Yamei,et al.Anti-inflammation and Regulation of HIF-1α/VEGF of 3 Kinds of Borneolum in Prevention and Treatment of AMI Model Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(19):61-72.
王立映,王建,樊亚梅等.3种冰片防治AMI模型大鼠的抗炎及调控HIF-1α/VEGF[J].中国实验方剂学杂志,2022,28(19):61-72. DOI： 10.13422/j.cnki.syfjx.20221009.

WANG Liying,WANG Jian,FAN Yamei,et al.Anti-inflammation and Regulation of HIF-1α/VEGF of 3 Kinds of Borneolum in Prevention and Treatment of AMI Model Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(19):61-72. DOI： 10.13422/j.cnki.syfjx.20221009.

摘要

目的

探讨艾片（左旋龙脑）、天然冰片（右旋龙脑）、冰片（合成龙脑）不同剂量对实验性急性心梗（AMI）模型大鼠心电生理及抗炎、调控缺氧诱导因子-1

（HIF-1

）/血管内皮生长因子（VEGF）心血管保护的可能机制。

方法

SD雄性成年大鼠，按体重随机分为假手术组、模型组、溶剂模型组、硝酸甘油组、天然冰片高、中、低剂量（0.6、0.3、0.15 g·kg

-1

）组、艾片及合成冰片高、中、低剂量（0.2、0.1、0.05 g·kg

-1

）组，每组10只。按10 mL·kg

-1

灌胃，预给药3 d，末次给药30 min后，施冠状动脉左前降支（LAD）结扎造模，将模型成功大鼠连续治疗3 d。采用BL-420N生物系统分析造模前后及治疗3 d后心电图及心率变异性（HRV），实时荧光定量聚合酶链式反应（Real-time PCR）检测心肌组织中白细胞介素-1

（IL-1

）、白细胞介素-6（IL-6） mRNA表达量，蛋白免疫印迹法、免疫组织化学法检测血管内皮生长因子受体1（VEGFR1）、HIF-1

、CD34蛋白表达水平。

结果

与假手术组比较，模型组造模当天及干预3 d后心率、心电ST段、T波、QRS时限、QTC间期、Q波显著升高，HRV及T波明显改变（

0.05，

0.01）；与溶剂模型组比较，造模当天艾片中、低剂量组、天然冰片组心率，艾片组、天然冰片高、中剂量、冰片高剂量组ST波幅，艾片组、天然冰片中、低剂量、冰片高剂量组HRV参数，艾片高、中剂量、天然冰片低剂量、冰片组低频与高频范围内的功率谱比值（LF/HF），艾片、冰片高剂量、天然冰片中剂量组T波波幅，艾片中、低剂量、天然冰片高、中剂量组QTC间期，艾片与天然冰片各自高、低剂量、冰片组QRS时限，均明显减小或缩短（

0.05，

0.01）；治疗3 d后艾片组、天然冰片高、中剂量、冰片中剂量组心率，艾片组、天然冰片高、中剂量、冰片高剂量组的ST段波幅，艾片与天然冰片各自高剂量、冰片高、中剂量组的QTC间期与QRS时限及Q波波幅，艾片中剂量组QRS时限，天然冰片中剂量组QTC间期、冰片低剂量组Q波，皆显著减小或缩短（

0.01）；艾片与天然冰片各自中、低剂量、冰片高、中剂量组的IL-1

、IL-6 mRNA表达量显著下调（

0.01）；艾片、天然冰片各自高、中剂量、冰片高、低剂量组LF/HF明显减小（

0.05，

0.01）；艾片高剂量、天然冰片组、冰片高、低剂量组HRV及天然冰片高、中剂量、冰片高剂量组T波波幅显著增大；艾片中、低剂量、天然冰片低剂量、冰片高剂量组HIF-1

、VEGFR1、CD34蛋白，天然冰片中剂量组VEGFR1、CD34蛋白表达明显上调（

0.05，

0.01）。

结论

3种冰片防治给药可不同程度改善AMI模型大鼠心率、心率变异性、心电图，可能会通过抗炎、促血管新生而发挥心肌保护作用。综合效应提示艾片较优，天然冰片略次、冰片次之。

Abstract

Objective

To investigate the possible mechanism of different doses of

-Borneolum，Borneolum，and Borneolum Syntheticum in the electrophysiology，anti-inflammation，and regulation of hypoxia inducible factor-1

（HIF-1

）/vascular endothelial growth factor （VEGF） cardiovascular protection of the experimental acute myocardial infarction （AMI） rats.

Method

SD male adult rats were randomly divided into thirteen groups according to their body weight，namely the sham operation group，the model group，the solvent model group，the nitroglycerin group，the Borneolum high，medium，and low-dose （0.6，0.3， 0.15 g·kg

-1

） groups，the

-Borneolum high，medium，and low-dose （0.2，0.1， 0.05 g·kg

-1

） groups，and the Borneolum Syntheticum high，medium，and low-dose （0.2，0.1， 0.05 g·kg

-1

） groups，with 10 rats in each group. Rats were given 10 mL·kg

-1

by gavage for 3 d of pre-administration. Thirty minutes after the last administration，the left anterior descending coronary artery （LAD） was ligated to induce the model，and the successful rat model was continuously treated for 3 d. BL-420N biosystem was used to analyze the electrocardiogram （ECG） and heart rate variability （HRV） before and after modeling and after 3 d of treatment. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA expressions of interleukin-1

（IL-1

） and interleukin-6 （IL-6） in the myocardial tissue Western blot and immunohistochemistry were used to determine the protein expression levels of VEGF receptor 1 （VEGFR1），HIF-1

，and CD34.

Result

Compared with the sham operation group，the model group significantly increased the heart rate，ECG ST wave，T wave，QRS duration，QTC interval，and Q wave on the day of modeling and after 3 d of treatment，and significantly changed HRV and T wave （

0.05，

0.01）. As compared with the solvent model group，on the day of modeling，the heart rate of the

-Borneolum medium and low-dose groups and the Borneolum groups，the ST wave of the

-Borneolum groups，the Borneolum high and medium-dose groups，and the Borneolum Syntheticum high-dose group，HRV parameters of the

-Borneolum groups，the Borneolum medium and low-dose groups，and the Borneolum Syntheticum high-dose group，LF/HF of the

-Borneolum high and medium-dose group，the Borneolum low-dose group，and the Borneolum Syntheticum groups，T wave of the L-Borneolum high-dose group，the Borneolum Syntheticum high-dose group，and Borneolum medium-dose group，QTC interval of the

-Borneolum medium and low-dose groups and the Borneolum high and medium-dose groups，and QRS duration of the

-Borneolum high and low-dose groups，the Borneolum high and low-dose groups，and the Borneolum Syntheticum groups were significantly reduced or shortened （

0.05，

0.01）. After 3 d of treatment，the heart rate of the

-Borneolum groups，the Borneolum high and medium-dose groups，and the Borneolum Syntheticum medium-dose group，ST wave of the

-Borneolum group，the Borneolum high and medium-dose groups，and the Borneolum Syntheticum high-dose group，OTC interval，ORS duration，and Q wave of the

-Borneolum high-dose group，the Borneolum high-dose group，and the Borneolum Syntheticum high and medium-dose groups，QRS duration of the

-Borneolum medium-dose group，QTC interval of the Borneolum medium-dose group，and Q wave of the Borneolum Syntheticum low-dose group were all significantly reduced or shortened（

0.01）. The mRNA expressions of IL-1

and IL-6 in the

-Borneolum medium and low-dose groups，the Borneolum medium and low-dose groups，and the Borneolum Syntheticum high and medium-dose groups were significantly down-regulated（

0.01），and LF/HF in the

-Borneolum high and medium-dose groups，the Borneolum high and medium-dose groups，and the Borneolum Syntheticum high and low-dose groups were significantly reduced （

0.05，

0.01）. HRV in the

-Borneolum high-dose group，the Borneolum groups，and the Borneolum Syntheticum high and low-dose groups，and T wave in the Borneolum high and medium-dose groups and the Borneolum Syntheticum high-dose group were increased significantly. The protein expressions of HIF-1

，VEGFR1，and CD34 in the

-Borneolum medium and low-dose groups，the Borneolum low-dose group，and the Borneolum Syntheticum high-dose group were significantly up-regulated，as well as those of VEGFR1 and CD34 in the Borneolum medium-dose group （

0.05，

0.01）.

Conclusion

The 3 kinds of Borneolum improves the heart rate，heart rate variability，and electrocardiogram of AMI model rats to different degrees，and may play a myocardial protective effect by anti-inflammation and promotion of angiogenesis. The combined effect suggests that L-Borneolum has the superior effect next to Borneolum，and Borneolum Syntheticum has the inferior effect.

关键词

3种冰片心肌梗死心肌电生理炎症因子血管新生

Keywords

3 kinds of Borneolummyocardial infarctionmyocardial electrophysiologyinflammatory factorsangiogenesis

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⁰

Anti-inflammation and Regulation of HIF-1α/VEGF of 3 Kinds of Borneolum in Prevention and Treatment of AMI Model Rats

DOI：10.13422/j.cnki.syfjx.20221009

摘要

Abstract

关键词

Keywords

references