OBJECTIVE  To explore the protective effect of Siegesbeckiae Herba on cerebral ischemia-reperfusion injury rats and human umbilical vein endothelial cells(HUVECs) based on miR-21/VEGF/Akt signaling pathway.

METHODS  The 30 rats were randomly divided into sham operation group, model group, low dose Siegesbeckiae Herba granula group, high dose Siegesbeckiae Herba granula group and positive control group. The cerebral ischemia-reperfusion injury model of rats was prepared by thread embolization method in other groups except sham operation group. After the model, Siegesbeckiae Herba group was administrated with different doses of formula granules of Siegesbeckiae Herba. The sham operation group and model group were administrated with equal volume normal saline, and the positive control group was administrated with 6 mg·kg⁻¹ nimodipine, continuous administration for 7 d. The modified neurological severity score(mNSS) was used to evaluate the neurological recovery in each group. The expressions of recombinant vascular endothelial growth factor A(VEGFA), phosphoinositide3-kinase(PI3K), protein kinase B(Akt) and platelet derived growth factor subunit B(PDGFB) were detected by Western blotting. The expressions of miR-21, platelet endothelial cell adhesion molecule-1(CD31), leukocyte differentiation antigen 34(CD34), angiopoietins-2(Ang-2) and VEGFA in ischemic brain were detected by real-time PCR. At the same time, HUVECs oxygen-glucose deprivation/recovery(OGD/R) model was established and randomly divided into blank control group, model group, Siegesbeckiae Herba group, Siegesbeckiae Herba+miR-210-5p inhibitor group and Siegesbeckiae Herba+inhibitor negative control group. The cell activity was detected by CCK-8 method. Lumen formation test was performed to detect the angiogenesis. Real-Time PCR was used to detect the expression of miR-21 and other genes, and Western blotting was used to detect the expression of PI3K and other proteins, and double luciferase assay was used to verify that VEGFA was the target gene of miR-21.

RESULTS  Compared with model group, Siegesbeckiae Herba could promote the recovery of nerve function and up-regulate the expression of key signal molecules of miR21/VEGF pathway in ischemic rats. Moreover, it could enhance the cellular activity of HUVECs in OGD/R model, up-regulate the expression of miR-21 in HUVECs cells, activate VEGF pathway, improve the expression of PI3K, p-Akt and Akt protein in HUVECs cells, and promote angiogenesis.

CONCLUSION  Siegesbeckiae Herba granules promote angiogenesis through miR-21 up-regulation of VEGF/Akt signaling pathway, thereby improving cerebral ischemia-reperfusion injury.