补阳还五汤对脑出血大鼠血肿周围新生血管整合素α_Vβ_3和β_3亚基表达的影响

Effect of Buyang Huanwu Decoction on Expression of Integrin α_Vβ_3 and β_3 Subunits in New Vessels Around the Hemotoma in Rats with Cerebral Hemorrhage

目的通过观察益气活血中药补阳还五汤对脑出血大鼠血肿周围新生血管内皮整合素αVβ3和整合素β3亚基表达的影响,探讨益气活血法治疗脑出血的作用机制。方法 150只SD大鼠随机分为假手术组、模型组、益气组、活血组、益气活血组(补阳还五汤),通过立体定位向脑内苍白球注入Ⅶ型胶原酶0.5 U建立脑出血模型。假手术和模型组灌服蒸馏水,余各组灌服补阳还五汤及其益气组分、活血组分药物。运用免疫组织化学方法,并对结果进行半定量分析,检测各组术后3、7、14、21、28 d各时点血肿周围新生血管内皮整合素αVβ3和整合素β3亚基的时空表达。结果除假手术组,各组新生血管内皮整合素αVβ3和β3亚基的表达趋势大致相近,7 d时各组表达达到高峰,益气活血组高峰延长至14 d,且各时点的表达较模型组增高(P<0.05)。结论补阳还五汤通过益气活血作用,能调节脑出血大鼠血肿周围新生血管整合素αVβ3和β3亚基的表达;通过参与脑出血后的血管新生,影响微血管系统重建,从而达到修复损伤组织的目的 。

Objective To investigate the effect of Buyang Huanwu Decoction（BHD）, a classical prescription with the actions of tonifying qi and activating blood, on expression of integrin αvβ3 and β3 subunit in new vessels around the hemotoma in rats with cerebral hemorrhage, and to explore its possible therapeutic mechanism. Methods One hundred and fifty Sprague-Dawley rats were divided into five groups randomly： sham-operation group（SO）, model group, tonifying qi group, activating blood group, and BHD group. Cerebral hemorrhage（CH） model was established by intraeerebral stereotactic injection of collagenase type VII 0.5 U into right globus pallidus. SO group and the model group were given distilled water orally, tonifying qi group was given the decoction of qi-tonifying herbs, activating blood group was given the decoction of blood-activating herbs, and BHD group was given BHD. The expression of integrin αvβ3 and β3 subunit was evaluated by immunohistochemical method, and the number of positive expression in new vessels around the hemotoma were analyzed semi-quantitatively at day 3, 7, 14, 21 and 28 after the operation. Results Immunohistochemical results showed that expression of integrin αvβ3 was as the same as that of β3 subunit in all of the groups except SO group. The expression of integrin αvβ3 and β3 subunit appeared on day 3 and reached a peak on day 7, then weakened gradually; in BHD group the peak continued till day 14, and the expression level at various time points was higher than that in the model group（P 〈 0.05 ）. Conclusion BHD can promote the recovery of rats with cerebral hemorrhage through up-regulating the expression of integrin αvβ3 and β3 subunit around the hemo- toma, and through promoting formation of new vessels and the reconstruction of microvascular networks.