Mechanism of Tongqiao Dingxuan Decoction regulating glycolysis to improve angiogenesis in rats with cerebral ischemia
Objective To explore the molecular mechanism of Tongqiao Dingxuan Decoction(TQDXD)on cerebral ischemia-induced angiogenesis,and to discuss its possible mechanism of action based on the glycolysis pathways.Methods A total of 40 rats were used,six rats were randomly selected as sham-operated group,and the rest were used to establish a cerebral ischemia model by the method of middle cerebral artery occlusion.Twenty-four rats with successful modeling were randomized into model,butylphthalide,combination,and TQDXD groups,with six rats in each group.Sham-operated and model groups were treated with distilled water 10 mL/(kg·d),butylphthalide group with butylphthalide 54 mg/(kg·d),combination group with butylphthalide 54 mg/(kg·d)and TQDXD 14.6 g/(kg·d),and TQDXD group with TQDXD 14.6 g/(kg·d).All the drugs and distilled water were administered by gavage.After 3 d of intervention,the neurological function of the rats was scored using the Zea-Longa method;the extent of cerebral infarction was determined by TTC staining;the levels of lactate,adenosine triphosphate(ATP),and glucose were measured by ELISA;the protein expressions of glucose transporter 1(GLUT1),hexokinase 2(HK2),and lactate dehydrogenase A(LDHA),as well as changes in microvessel density were examined by immunohistochemistry.Results Compared with the sham-operated group,the model group exhibited significant neurological deficits and obviously increased volume ratio of cerebral infarction(P<0.05),elevated lactate level(P<0.05),decreased ATP and glucose levels(P<0.05),higher protein expressions of GLUT1,HK2,and LDHA(P<0.05),and increased microvessel density(P<0.05).Compared with the model group,the butylphthalide group showed significantly reduced neurological deficits and volume ratio of cerebral infarction(P<0.05),and increased microvessel density(P<0.05),with no significant changes in lactate,ATP,and glucose levels(P>0.05),nor in the protein expressions of GLUT1,HK2,and LDHA(P>0.05);both the combination and TQDXD groups showed significantly reduced neurological deficits and volume ratio of cerebral infarction(P<0.05).increased lactate,TP,and glucose levels(P<0.05),and significantly elevated protein expressions of GLUT1,HK2,and LDHA,and microvessel density(P<0.05).Compared with the combination group,the butylphthalide group exhibited increased cerebral infarction area(P<0.05),decreased lactate,ATP,and glucose levels(P<0.05),lower protein expressions of GLUT1,HK2,and LDHA(P<0.05),and reduced microvessel density(P<0.05);the TQDXD group showed increased cerebral infarction area(P<0.05)and decreased microvessel density(P<0.05),with no significant changes in the levels of lactate,ATP,and glucose(P>0.05),nor in the protein expressions of GLUT1,HK2,and LDHA(P>0.05).Conclusion TQDXD has a certain neuroprotective effect on cerebral ischemia model,and its mechanism may be related to regulating glycolysis pathways to promote angiogenesis.
Tongqiao Dingxuan Decoctionglycolysiscerebral ischemiaangiogenesisglucose transporter 1hexokinase 2lactate dehydrogenase A
万方数据
维普
