[Effect of Xinmailong on hypoxia-inducible factor-1alpha expression in neonatal rats with asphyxia].
OBJECTIVE
Xinmailong, a compound extracted from Periplaneta americana, is used for the treatment of cardiovascular diseases. This study investigated the effects of Xinmailong on myocardial hypoxia-inducible factor-1alpha (HIF-1alpha) and plasma endothelin-1(ET-1) levels in neonatal rats with asphyxia and explored the protection mechanism of Xinmailong in hypoxia-ischemic myocardial injury.


METHODS
Seven-day-old Sprague-Dawley rats were randomly divided into three groups (n=30 each): sham-operated, asphyxia, Xinmailong-treated asphyxia. Each group was randomly subdivided into three groups according to the observed time points: 6 hrs, 24 hrs and 72 hrs. Xinmailong (5 mg/kg) was intraperitoneally injected to the rats in the Xinmailong-treated group five minutes before asphyxia. Myocardial HIF-1alpha expression, and plasma ET-1 and creatine kinase (CK) levels were measured. The histopathologic changes of the myocardium were observed by hematoxylin-eosin staining.


RESULTS
Four rats died in the asphyxia group while only one died in the Xinmailong-treated group during the experiment. The plasma ET-1 and CK levels as well as myocardial HIF-1alpha expression increased at 6 hrs, reached a peak at 24 hrs, and declined at 72 hrs after asphyxia in the asphyxia group, being higher than that in the sham-operated group (P<0.01). Myocardial ischemia was observed in the three time points, and cell necrosis occurred at 24 hrs after asphyxia in the asphyxia group. Myocardial HIF-1alpha expression was positively correlated with plasma ET-1 levels (r=0.876, P<0.01). In the Xinmailong-treated group, plasma levels of CK and ET-1 as well as myocardial HIF-1alpha expression were significantly lower than those in the asphyxia group (P<0.01). Myocardial ischemia was alleviated and no cell necrosis was found in the Xinmailong-treated group.


CONCLUSIONS
Asphyxia leads to increase in myocardial HIF-1alpha expression and plasma levels of ET-1 and CK. Xinmailong can reduce the myocardial expression of HIF-1alpha and decrease plasma ET-1 levels, thus alleviating hypoxia-ischemic myocardial injury.
Huang
Li-Xin
LX
2006 Grade of Medical Department, Graduate School, Nanchang University, Nanchang, China.
Wu
Xing-Heng
XH
D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000378:metabolism*; D003402:Creatine Kinase / Q000097:blood; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis*; D007150:Immunohistochemistry; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy*; D009206:Myocardium / Q000473:pathology; D010526:Periplaneta / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019332:Endothelin-1; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D003402:Creatine Kinase