Buyang huanwu decoction promotes angiogenesis via vascular endothelial growth factor receptor-2 activation through the PI3K/Akt pathway in a mouse model of intracerebral hemorrhage.
Buyang huanwu decoction promotes angiogenesis via vascular endothelial growth factor receptor-2 activation through the PI3K/Akt pathway in a mouse model of intracerebral hemorrhage.
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补阳还五汤通过PI3K/Akt通路激活血管内皮生长因子受体2促进脑出血小鼠模型血管生成
DOI：
10.1186/s12906-015-0605-8
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发表时间：
2015-03-28
影响因子：
--
通讯作者：
Tang T
中科院分区：
文献类型：
--
作者：
Cui HJ;Yang AL;Zhou HJ;Wang C;Luo JK;Lin Y;Zong YX;Tang T
脑出血(ICH)是一种致命的卒中亚型，缺乏有效的治疗方法。脑出血后的血管生成是介导脑功能恢复和修复的重要反应。通过PI3K/Akt信号通路使血管内皮生长因子受体2(PVEGFR2)磷酸化，在介导细胞有丝分裂、血管生成和血管通透性等修复过程中起关键作用。本研究旨在探讨补阳还五汤通过磷脂酰肌醇3激酶(PI3K)/Akt信号通路激活血管内皮生长因子2(VEGFR2)对脑出血小鼠血管生成的影响。成年雄性昆明种小鼠(n = 50)随机分为假手术组和脑出血组，分别给予血管内皮生长因子受体2抑制剂SU5416、补阳还五汤和补阳还五汤 + SU5416治疗。向小鼠右侧苍白球注射VII型胶原酶诱导脑出血。补阳还五汤4.36 mg/kg灌胃给药。小鼠的神经功能通过改良的神经严重程度评分(MNSS)以及转弯和足部失误测试进行评估。通过腹腔注射5-溴脱氧尿苷(BrdU)来检测新生脑血管的生长情况。通过SU5416处理和检测VEGFR2的磷酸化以及PI3K/Akt信号的改变，以确定补阳还五汤对血管生成的影响是否部分是通过PI3K/Akt信号通路的VEGFR2的磷酸化来实现的。与未治疗的脑出血小鼠相比，补阳还五汤治疗组小鼠表现出：(1)神经功能障碍的显著恢复；(2)vWF+扩张脑血管中BrdU+核的增加；(3)脑微血管中VEGFR2的磷酸化免疫反应性增强(P<；0.05)；(4)PI3K和PACT在蛋白水平上的表达增加(P<；0.05)。这些有益的作用被SU5416逆转(P<；0.05)。补阳还五汤通过PI3K/Akt信号通路促进VEGFR2磷酸化，促进脑出血小鼠神经功能恢复和血管生成。
Intracerebral hemorrhage (ICH) is a fatal subtype of stroke that lacks effective treatments. Angiogenesis following ICH is an important response mediating brain recovery and repair. Phosphorylation of vascular endothelial growth factor receptor 2 (pVEGFR2) via PI3K/Akt signaling plays a key role in mediating cellular processes involved in repair, such as mitogenesis, angiogenesis, and vascular permeability. This study aimed to investigate the potential effects of Buyang Huanwu Decoction (BYHWD), a traditional Chinese medicine formula, on angiogenesis by VEGFR2 activation through the phosphatidylinositol 3 kinase (PI3K)/Akt signaling pathway in a mouse model of ICH. Adult male Kunming mice (n = 50) were randomly assigned into sham and ICH-operated groups and treated with one of the followings SU5416 (VEGFR2 inhibitor), BYHWT and BYHWT + SU5416. ICH was induced in mice by injecting collagenase (type VII) into the right globus pallidus of the mouse brain. BYHWD (4.36 g/kg) was administrated in mice by intragastric infusion. Neurological function was evaluated in mice by a modified Neurological Severity Scores (mNSS) as well as corner turn and foot-fault tests. Angiogenesis was examined by intraperitoneal injection of 5-bromodeoxyuridine (BrdU) in mice to quantify new brain vessel growth. SU5416 treatment and assessment of VEGFR2 phosphorylation as well as alterations in PI3K/Akt signaling were performed to determine whether the effect of BYHWD on angiogenesis was partly mediated by phosphorylation of VEGFR2 via the PI3K/Akt signaling pathway. We show that BYHWD treated mice exhibited (i) significantly better recovery from neurological dysfunction, (ii) increased BrdU+ nuclei in vWF+ dilated brain vessels and (iii) higher VEGFR2 phosphorylation immunoreactivity in brain microvessels (P <0.05), (iv) higher expression of PI3K and pAkt at the protein level (P <0.05) when compared to untreated ICH mice. These beneficial effects were reversed by SU5416 (P <0.05). BYHWD promoted neurological recovery and angiogenesis after ICH in mice by enhancing VEGFR2 phosphorylation through the PI3K/Akt signaling pathway.
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影响因子：
4.2
作者：
Reshef, Ayelet;Shirvan, Anat;Ziv, Ilan
通讯作者：
Ziv, Ilan
影响因子：
2.5
作者：
Kleim, Jeffrey A.;Boychuk, Jeffery A.;Adkins, DeAnna L.
通讯作者：
Adkins, DeAnna L.
影响因子：
5.4
作者：
Katoh M
通讯作者：
Katoh M
影响因子：
20.3
作者：
Lakshmikanthan, Sribalaji;Sobczak, Magdalena;Chrzanowska-Wodnicka, Magdalena
通讯作者：
Chrzanowska-Wodnicka, Magdalena
补阳还五汤治疗急性缺血性中风的临床疗效和安全性：19项随机对照试验的系统评价和荟萃分析
DOI：
10.1155/2012/630124
发表时间：
2012
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Hao CZ;Wu F;Shen J;Lu L;Fu DL;Liao WJ;Zheng GQ
通讯作者：
Zheng GQ