Effect Of Qi-tonifying And Stasis-eliminating Therapy On Expression Of Integrins In Angiogenesis Around The Hemotoma In Rat Brain Following Intracerebral Hemorrhage

Objective Intracerebral hemorrhage(ICH) is a common and often fatal stroke subtype, for which hospital admissions has increased gradually wordwide in recent years, but mortality has not fallen. This serious disease have threated to public health and quality of life. Specific treatment approaches include management of intracranial pressure, open surgical to remove clot, but available theray is vacancy. Most people who suffered from ICH show qi-deficiency and blood-stasis syndrome in accordance with Traditional Chinese Medicine(TCM) theory. QTSE therapy(益气活血法) is the representative treatment for this syngrome. Buyang Huanwu Decoction (BYHWD), as the classical recipe for QTSE, has definite therapeutic effect in clinical practice. Integrins are a kind of cell adhesion molecule, which bind extracellular matrix (ECM) proteins and enable not only cell adhesion and cytoskeleton organization but also transduction of critical signals into the cells to promote the programs including survival, proliferation, differentiation, and migration. So far, the studies of angiogenesis stimulated by integrins in central nervous system (CNS) are focused on CNS tumor and cerebral infarction, also, our previous studies have documented that the reconstruction of microvascular networks is promoted by angiogenesis in the damaged areas after ICH. In present work, we dealt the collagenase-induced ICH rats with QTSE therapy, used immunohistochemical method, analyzed the result semi-quantitatively, investigated the effects of QTSE on expression of integrins in angiogenesis around the hemotoma in the brains of ICH in rats.Methods One hundred and fifty Sprague-Dawley rats were divided into five groups randomly:the sham-operative (SO) group (n=30), the model group (n=30), the QTSE-treated group (n=30), the Qi-tonifying (QT)-treated group (n=30), and the stasis-eliminating (SE)-treated group (n=30). All the rats were established into an intracerebral hemorrhage (ICH) model by intracerebral stereotactic injection of collagenase type Ⅶ0.5U into right globus pallidus except those in the SO group (saline injected instead) and the latter three group were orally administered with Buyang Huanwu Decoction or with some of its components for qi-tonification and for stasis-elimination, respectively. To the SO and model groups, normal saline solutions were given instesd. The expressions of intgrins were evaluated by immunohistochemical method, and the number of positive expression in angiogenesis around the hemotoma at3rd、7st、14st、21st、28st days were analyzed semi-quantitatively.Results Immunohistochemical results showed that there were almost no expression of integrins in SO group. Integrin αvβ3、α1β1、α6β1、 and β3、 α1、 α6submits share overlapping expression patterns. Integrin αvβ3and β3subunit were detected at3days around hemotoma, reached a peak at7days, then weakened gradually on14-28days. In QTSE group, the peak was persisted on14days and the expression were higher than the model group at the some corresponding time points. Integrin α5submit positive microvascular were detected at3days around hemotoma, the expression increased from7-21days, the peak persisted from14to21days, then declined on28days, the QTSE group were significantly higher than the that in model group from7-28days. Integrin α1β1and α1submit were observed in rat brains at3days, furthermore, the exprseeion increased gradually from day7, peaked at day14and persisted at day28, the QTSE group were significantly higher than the model group at the corresponding time points from7-28days. Integrin α6β1and α6submit showed low levels of expression at3-7days, immediately, the exprseeion peak occurred at14days, lasted to day28, the QTSE group were significantly higher than the model group at the corresponding time points from14-28days.Conclusions1.ICH may change the expression of integrins in angiogenesis around the hemotoma in the brains of ICH in rats.2. QEST therapy may modulate angiogenesis via upregulation of the expression of integrins around the hemotoma to promote the reconstruction of microvascular networks in the damaged areas.