Effects of Radix et Rhizoma Rhodiolae Kirilowii on expressions of von Willebrand factor, hypoxia-inducible factor 1 and vascular endothelial growth factor in myocardium of rats with acute myocardial infarction.
OBJECTIVE
To investigate the effects of Radix et Rhizoma Rhodiolae Kirilowii on angiogenesis and expressions of hypoxia-inducible factor 1alpha (HIF-1alpha), hypoxia-inducible factor 1beta (HIF-1beta) and vascular endothelial growth factor (VEGF) in myocardium of rats with acute myocardial infarction (AMI), to elucidate the possible mechanism of Radix et Rhizoma Rhodiolae Kirilowii in promoting angiogenesis, and to investigate that whether or not salidroside could be considered as the effective component of Radix et Rhizoma Rhodiolae Kirilowii with regard to the effects mentioned above.


METHODS
Thirty-six male Wistar rats had the anterior descending branch of coronary artery ligated as AMI model. Rats were fed with normal saline (untreated group), Radix et Rhizoma Rhodiolae Kirilowii solution (Radix et Rhizoma Rhodiolae Kirilowii group) or salidroside solution (salidroside group) from 7 days before until 7 days after the operation, with twelve rats in each group. All rats were sacrificed 7 days after the operation. Immunohistochemical assay (IHC) was used for detecting the expression of von Willebrand factor (vWF); TaqMan real-time quantitative polymerase chain reaction (PCR) assay was employed for detection of the levels of HIF-1alpha, HIF-1beta and VEGF mRNAs; Western blot analysis was used for detection of the corresponding protein levels.


RESULTS
Results of IHC index showed that both at infarct border zone and non-infarct zone, the expressions of vWF were significantly increased in Radix et Rhizoma Rhodiolae Kirilowii group as compared with the untreated group (P<0.05). The expressions of HIF-1alpha, HIF-1beta and VEGF mRNAs and the expressions of HIF-1alpha and VEGF proteins were significantly increased in the Radix et Rhizoma Rhodiolae Kirilowii group as compared with the untreated group (P<0.01). The level of HIF-1beta protein in the Radix et Rhizoma Rhodiolae Kirilowii group was also higher than that in the untreated group but the difference was not statistically significant (P>0.05). All the expression levels, including those of vWF, HIF-1alpha, HIF-1beta and VEGF, in the salidroside group were higher than those in the untreated group while lower than those in the Radix et Rhizoma Rhodiolae Kirilowii group.


CONCLUSIONS
Radix et Rhizoma Rhodiolae Kirilowii may promote angiogenesis in myocardium of rats with AMI through elevating the expressions of HIF-1alpha, HIF-1beta, and VEGF. Salidroside may be one of the effective components in Radix et Rhizoma Rhodiolae Kirilowii, which increases the expressions of HIF-1alpha, HIF-1beta and VEGF during ischemia or hypoxia.
Department of Cardiology, Huashan Hospital, and Department of Animal Research, Fudan University, Shanghai 200040, China.
Xiu-fang
XF
Gao
Hai-ming
HM
Shi
Tao
T
Sun
Hong
H
Ao
D000818:Animals; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use; D005960:Glucosides / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology; D008517:Phytotherapy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D027343:Rhizome / Q000737:chemistry; D029771:Rhodiola / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism*
D004365:Drugs, Chinese Herbal; D005960:Glucosides; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010636:Phenols; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D014841:von Willebrand Factor; C009172:rhodioloside