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[Effect of ginsenoside Rg1 on angiogenesis after neonatal hypoxia ischemia brain damage in rats]
De-Jian Wang1, Qiao-Yun Li, Shi-Jun Xu
1Department of Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.
Objective:
To investigate effects of ginsenoside Rg1 on angiogenesis in neonatal rats with hypoxia ischemia brain damage (HIBD), and explore the possible mechanism.
Methods:
Fifty-four of 10-day-old SD rats were randomly divided into sham-operation group (n = 6), hypoxia-ischemia brain damage group (n = 24) and ginsenoside Rg1 treatment group (n = 24). SD rats in HIBD group and Rg1 group were treated by separation and ligation of right common carotid artery (CCA) and subsequently exposed to hypoxia for 2.5 hours, and those in sham group were treated by only separation of right CCA, without ligation or exposure to hypoxia. Intraperitoneal injection of 0.1 mL normal saline (NS) containing 40 mg/kg Rg1 was performed immediately after operation in Rg1 group, and such process was repeated every 24 h for 3 days. Intraperitoneal injection of 0.1 mL pure NS was performed in both HIBD group and sham group, in the same way as that of in Rg1 group. General state of SD rats after operation was monitored, 4, 8, 24 and 72 hours after HIBD, animals were executed and the right side of brain tissue was separated for further process. Protein expression of both hypoxia inducible factor 1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) were detected by both Western blot and immunohistochemistry. Immunohistochemistry for von willebrand factor (vwf) was used to labeling micro vessels.
Results:
All rats survived to the end of the study and neurological dysfunction was observed in both HIBD group and Rgl group, but not in sham group. Expression of HIF-1alpha protein in HIBD group was increased at 4, 8, 24 and 72 h, compared to that in sham group (P < 0.05). Expression of HIF-1alpha protein in Rg1 group was increased compared to that in HIBD group at the same time points (P < 0.05). Expression of VEGF protein in HIBD group was increased at 4, 8, and 24 h, compared to that in sham group (P < 0.05). Expression of VEGF protein in Rg1 group was increased at 24 and 72 h compared to that in HIBD group at the same time point (P < 0.05). Number of vwf-positive cells at 24 and 72 h in HIBD group was increased compared to that in sham group (P < 0.05), and number of vwf-positive cells at 72 h in Rg1 group was increased compared to that in HIBD group at the same time point (P < 0.05).
Conclusion:
Rg1 could facilitate angiogenesis after HIBD in Neonatal rats by strengthening and stabilizing HIF-1alpha/VEGF signaling pathway.
