Preventive Effect and Underlying Mechanism of Tetramethylpyrazine on Hypobaric and Hypoxic Pulmonary Hypertension in Rats
- VernacularTitle:川芎嗪对大鼠低压低氧性肺动脉高压的预防作用及初步机制探讨
- Author:
Youwei LI
;
Weihong LIU
;
Bangguo LIU
;
Mingchun LI
;
Yang LIU
;
Qing MIAO
;
Zhuo XIANG
- Keywords:
Tetramethylpyrazine;
Hypobaric and hypoxic;
Pulmonary hypertension;
Nitric oxide;
Endothelin-1;
Hypoxic-inducible factor-1;
Vascular endothelial growth factor
- From:
China Pharmacist
2017;20(4):607-611
- CountryChina
- Language:Chinese
-
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 groups:the 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 (P<0.05 or P<0.01),and those of TMP group were obviously lower than those of hypobaric and hypoxic group (P<0.05 or P<0.01).The condition of hypobaric and hypoxic had no significant effect on mCAP,and there were no significant differences among the groups (P>0.05).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.