Anti-inflammation and Regulation of HIF-1α/VEGF of 3 Kinds of Borneolum in Prevention and Treatment of AMI Model Rats / 中国实验方剂学杂志

ABSTRACT

ObjectiveTo investigate the possible mechanism of different doses of L-Borneolum，Borneolum，and Borneolum Syntheticum in the electrophysiology，anti-inflammation，and regulation of hypoxia inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF） cardiovascular protection of the experimental acute myocardial infarction （AMI） rats. MethodSD 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 L-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-1β （IL-1β） 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-1α，and CD34. ResultCompared 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 （P<0.05，P<0.01）. As compared with the solvent model group，on the day of modeling，the heart rate of the L-Borneolum medium and low-dose groups and the Borneolum groups，the ST wave of the L-Borneolum groups，the Borneolum high and medium-dose groups，and the Borneolum Syntheticum high-dose group，HRV parameters of the L-Borneolum groups，the Borneolum medium and low-dose groups，and the Borneolum Syntheticum high-dose group，LF/HF of the L-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 L-Borneolum medium and low-dose groups and the Borneolum high and medium-dose groups，and QRS duration of the L-Borneolum high and low-dose groups，the Borneolum high and low-dose groups，and the Borneolum Syntheticum groups were significantly reduced or shortened （P<0.05，P<0.01）. After 3 d of treatment，the heart rate of the L-Borneolum groups，the Borneolum high and medium-dose groups，and the Borneolum Syntheticum medium-dose group，ST wave of the L-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 L-Borneolum high-dose group，the Borneolum high-dose group，and the Borneolum Syntheticum high and medium-dose groups，QRS duration of the L-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（P<0.01）. The mRNA expressions of IL-1β and IL-6 in the L-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（P<0.01），and LF/HF in the L-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 （P<0.05，P<0.01）. HRV in the L-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-1α，VEGFR1，and CD34 in the L-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 （P<0.05，P<0.01）. ConclusionThe 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.