目的 觀察當(dāng)歸芍藥散活血利水不同配伍對(duì)缺血性腦卒中雄性小鼠血管新生的影響，并探討其對(duì)血管新生相關(guān)因子的影響。方法 采用成年C57雄性小鼠制備大腦中動(dòng)脈遠(yuǎn)端梗阻（dMCAO）模型，隨機(jī)分為7組，假手術(shù)組、模型組、原方組（當(dāng)歸、川芎、白芍、澤瀉、茯苓、白術(shù)生藥劑量分別為68.3、68.3、363.8、181.9、91.0、91.0 mg/kg）、在原方基礎(chǔ)上，將活血的3味藥加倍的活血倍量（當(dāng)歸、川芎、白芍、澤瀉、茯苓、白術(shù)生藥劑量分別為136.6、136.6、727.6、181.9、91.0、91.0 mg/kg）組、將利水的3味藥加倍的利水倍量（當(dāng)歸、川芎、白芍、澤瀉、茯苓、白術(shù)生藥劑量分別為68.3、68.3、363.8、363.8、180.2、180.2 mg/kg）組、僅有活血的3味藥且加倍的活血（當(dāng)歸、川芎、白芍生藥劑量分別為136.6、136.6、727.6 mg/kg）組，以及僅有利水的3味藥且加倍的利水（澤瀉、茯苓、白術(shù)生藥劑量分別為363.8、180.2、180.2 mg/kg）組。采用轉(zhuǎn)棒實(shí)驗(yàn)對(duì)小鼠進(jìn)行神經(jīng)功能評(píng)分；通過免疫熒光染色檢測(cè)血管新生；采用Pearson相關(guān)性分析進(jìn)行神經(jīng)功能與血管數(shù)量相關(guān)性分析；采用通過蛋白芯片及Western blotting檢測(cè)對(duì)血管新生相關(guān)因子的影響。結(jié)果 與模型組及原方組比較，活血倍量組小鼠在轉(zhuǎn)棒上的停留時(shí)間顯著增加，差異有統(tǒng)計(jì)學(xué)意義（P<0.05、0.01）；CD31⁺細(xì)胞數(shù)及CD31⁺/BrdU⁺細(xì)胞數(shù)顯著增加（P<0.05、0.01），且活血倍量組改善神經(jīng)功能與血管數(shù)量具有相關(guān)性；進(jìn)一步分子機(jī)制研究發(fā)現(xiàn)，活血倍量組顯著增加了堿性成纖維細(xì)胞生長(zhǎng)因子（FGF-2）、基質(zhì)細(xì)胞衍生因子-1α（SDF-1α）、血管內(nèi)皮生長(zhǎng)因子（VEGF）的表達(dá)（P<0.05、0.01、0.001）。結(jié)論 當(dāng)歸芍藥散的活血倍量配伍對(duì)缺血性腦損傷小鼠血管新生的貢獻(xiàn)度最大。

Objective To observe the effects of different compatibility of Danggui Shaoyaosan (DSS) for activating blood circulation and diuresis on the angiogenesis of male mice with ischemic stroke, and explore its effect on angiogenesis-related factors. Methods Adult C57 male mice were made with a model of distal middle cerebral artery obstruction (dMCAO model). They were randomly divided into seven groups, the sham group, the model group and the original prescription group (the crude drug dosage of Angelicae Sinensis Radix, Chuanxiong Rhizoma, Angelicae Dahuricae Radix, Alismatis Rhizoma, Poria, Atractylodis Macrocephalae Rhizoma were 68.3, 68.3, 363.8, 181.9, 91.0, 91.0 mg/kg respectively). On the basis of the original formula, the doubling blood activating volume group (the crude drug doses of Angelicae Sinensis Radix, Chuanxiong Rhizoma, Angelicae Dahuricae Radix, Alismatis Rhizoma, Poria, Atractylodis Macrocephalae Rhizoma were 136.6, 136.6, 727.6, 181.9, 91.0, 91.0 mg/kg respectively), the doubling body fluidtransportation and transformation volume group (the crude drug doses of Angelicae Sinensis Radix, Chuanxiong Rhizoma, Angelicae Dahuricae Radix, Alismatis Rhizoma, Poria, Atractylodis Macrocephalae Rhizoma were 68.3, 68.3, 363.8, 363.8, 180.2, and 180.2 mg/kg respectively), blood activating group (the crude drug dosage of Angelicae Sinensis Radix, Chuanxiong Rhizoma, Angelicae Dahuricae Radix were 68.3, 68.3, 363.8 mg/kg), body fluidtransportation and transformation (the crude drug dosage of Alismatis Rhizoma, Poria, Atractylodis Macrocephalae Rhizoma were 363.8, 180.2, 180.2 mg/kg). Mice were scored for neurological function. The angiogenesis was detected by immunohistochemistry. The angiogenesis-related factors were detected by protein array and Western blotting. Results Compared with the model group and the original prescription group, the residence time of mice in the doubling blood activating volume group was significantly increased (P<0.05, 0.01); the number of CD31⁺ cells and the number of CD31⁺/BrdU⁺ cells were significantly increased (P<0.05, 0.01), and the improvement of nerve function was correlated with the number of blood vessels in the doubling blood activating volume group; further molecular mechanism study found that the number of CD31⁺ cells and CD31⁺/BrdU⁺ cells in the doubling blood activating volume group was significantly increased (P<0.05, 0.01) The expression of basic fibroblast growth factor (FGF-2), stromal cell-derived factor-1 α (SDF-1 α) and vascular endothelial growth factor (VEGF) were increased (P<0.05, 0.01, 0.001). Conclusion The DSS's blood activating compatibility is the most significant contribution to nerve regeneration in mice with ischemic brain injury.

R285.5

國(guó)家自然科學(xué)基金資助項(xiàng)目（81573867、81473591）