益气活血法对脑出血大鼠脑内VEGF及其受体Flt-1和Flk-1 mRNA表达的影响

Effect of Yi-Qi Huo-Xue Therapy on Expression of VEGF and its Receptors Flt-1,Flk-1 mRNA in Rat Brains Following Intracerebral Hemorrhage

目的观察益气活血对脑出血大鼠脑内损伤区血管内皮生长因子(VEGF)mRNA及其受体Flt-1mR-NA和Flk-1mRNA表达的影响,探讨益气活血法的作用机制。方法通过立体定位向脑内苍白球注入Ⅶ型胶原酶0.5U建立脑出血模型。SD大鼠随机分为正常组、假手术组、模型组、益气活血组、益气组、活血组,分别灌服益气活血法代表方补阳还五汤全方及其益气组分、活血组分药物(剂量为临床70kg成人用量的3倍),运用逆转录聚合酶链式反应(RT-PCR)检测正常组及其它各组于造模术后1、4、7、14、21、28d各时间点VEGFmRNA、Flt-1mRNA和Flk-1mRNA的动态变化。结果正常组及假手术组不同时间点VEGFmR-NA、Flt-1mRNA和Flk-1mRNA均未见明显表达;模型组VEGFmRNA、Flt-1mRNA和Flk-1mRNA在脑出血后1d即开始表达,21d达到高峰,然后逐渐减弱;益气活血组VEGFmRNA、Flt-1mRNA和Flk-1mR-NA表达在7～21d明显高于其他各组,VEGFmRNA和Flk-1mRNA表达在术后14d达高峰,Flt-1mRNA在术后21d达高峰。结论益气活血法能促进脑出血大鼠脑内VEGFmRNA、Flt-1mRNA和Flk-1mRNA的表达而调整血管新生过程,可能是其促进组织修复的机制之一。

Objective： To investigate the mechanisms of Yi - Qi Huo - Xue therapy（YQHX） by observing its effects on expressions of the mRNA of vascular endothelial growth factor （VEGF）and the receptors Flt - 1, Flk - 1 in intracerebral hemorrhagic（ICH） rat brains. Methods： ICH was induced by injecting collagenase type Ⅶ stereotaxically into rat brain right globus pallidus. One hundred and fifty- five Sprague-Dawley rats were randomly divided into six groups, including normal control group（ n = 5）, sham group（ n = 30）, ICH model group（ n = 30）, YQHX - treated group（ n = 30）, YiQi - treated group（ n = 30） and HuoXue - treated group（ n = 30）, respectively administered orally with the classic YQHX prescription, Buyanghuanwu decoction, its YiQi and Huo xue compo- nents, all at the dosage three times that of a 70kg adult; The expression of mRNA of VEGF, FLT - 1 and Flk - 1 was assayed by reverse transcription- polymerase chain reaction（RT- PCR）at day 1,4,7,14,21 and 28 after the onset. Results： Nonsignifficant expression of VEGF mRNA in rat brains of normal or sham during the experiment; In model group, the expressions of VEGF mRNA,Flt - 1mRNA and Flk - 1mRNA appeared at ld, peaked at 21d, and then weakened gradually; The expressions of VEGF mRNA,Flt- 1mRNA and Flk - 1mRNA in YQHX -treated group were significantly higher than those in the other groups from 7d to 21d, and the expression of VEGF mRNA and Flk - 1mRNA in YQHX-treated group reached peak at 14d, but the expression of Flt - 1mRNA reached at 21 d. Conclusions： The Yi - Qi Huo - Xue therapy can promote the expressions of VEGFmRNA ,Flt - 1 mRNA and Flk -1mRNA in intracerebral hemorrhagic rats, which may be related with its promoting the reconstruction of the microvascular networks in the damaged zone.