Preventive Effect and Underlying Mechanism of Tetramethylpyrazine on Hypobaric and Hypoxic Pulmonary Hypertension in Rats / 中国药师

ABSTRACT

Objective:To investigate the preventive effect of tetramethylpyrazine (TMP) on hypoxic pulmonary hypertension in rats and the underlying mechanism.Methods:Thirty-six male Sprague-Dawley rats were randomly divided into three groupsthe normal control group,hypobaric and hypoxic group and TMP group (100 mg·kg-1·d-1).After the animal models of hypobaric and hypoxic pulmonary hypertension were established,mean pulmonary artery pressure (mPAP),mean carotid artery pressure (mCAP),ratio of right ventricular/(lift ventricular + interventricular septum) (RVHI) and morphological changes of pulmonary vessels were observed and the rates of wall thickness/external diameter (WT%) and wall area/total vascular area (WA%) were calculated.The contents of nitric oxide (NO),endothelin-1 (ET-1),hypoxic-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) were detected in serum after the 21-day treatment with TMP.Results:The values of mPAP,RVHI,WT% and WA% of hypobaric and hypoxic group were significant higher than those of the normal control group (P0.05).The values of NO in serum of hypobaric and hypoxic group was lower than those of the normal control group (P<0.05) and those of TMP group were obviously higher than those of hypobaric and hypoxic group (P<0.05).The values of ET-1,HIF-1α and VEGF in serum of hypobaric and hypoxic group were higher than those of the normal control group (P<0.05) and those of TMP group were obviously lower than those of hypobaric and hypoxic group (P<0.05).Conclusion:TMP can effectively prevent pulmonary hypertension induced by hypobaric and hypoxic and structural remodeling of pulmonary arterioles.The mechanism may be related to the content up-regulation of NO and activity down-regulation of ET-1,HIF-1α and VEGF in serum of rats.