| Background:Due to its high morbidity and mortality rate, ischemic cerebrovascular disease (ICVD) has become one of the leading diseases that endanger human's health nowadays without specific treatments. Therefore, it is of importance for biomedical researchers to look for new and effective drugs beneficial to the treatment of ICVD. The research of ICVD has been recently focused on improving the blood supply in the ischemic border zone. Vascular epithelial growth factor (VEGF) is not only the most potent factor to stimulate the growth of blood vessels so far; also it functions to protect neurons and promotes regeneration of neurons. A pool of evidence has shown that VEGF participates in the pathophysiological processes following cerebral ischemia and may play an essential role in the process. Therefore, exogenous VEGF application or induction of VEGF protein expression by some drugs may help the regeneration of microvessels in ischemic region thus rescuing the cerebral tissue from dying. Cumulating evidence has demonstrated traditional Chinese medicine is effective in the treatment ofcerebral occlusion. Dachuanxiongwan(DCXW), a traditional Chinese medical compound developed by Chengdu University of Traditional Chinese Medicine and other units with its wide pharmacological properties and has been used in the treatment of migraine. Moreover, clinical studies have also demonstrated its beneficial effects on the cerebral occlusion. This study is to provide further evidence to justify the use of DCXW in the treatment of ICVD by examining DCXW's protective effects against ICVD and its actions on VEGF expression. Materials and methods:The rat model with cerebral ischemia or reperfusion injury was established according to Zea-Longa by blocking cerebral artery with a nylon thread . Transient ischemia was obtained by removing the nylon thread from ICA 2 hours after occlusion, while permanent occlusion with the thread leads to permanent ischemia. Forty healthy male Sprague-Dawley rats (360~403 grams), following middle cerebral artery occlusion (MCAO) with 1-3 grading according to Longa, were randomly divided into four groups: (A), permanent ischemic group; (B),permanent ischemic group as group A with DCXW administration,4.13g/kg/d, twice a day for 3 days by gavaging; (C), transient ischemic group; (D), transient ischemic group as group C with DCXW administration same as group B,while the A and C group have the same volume of saline as group B and D. Seventy-two hours after occlusion or reperfusion, all rats were sacrificed and samples of cerebrum were obtained after in situ perfusion and fixation with 4% paraformaldehyde. All the samples were processed and embedded in paraffin and cut into two sets of 4 fim thick sections in a row every 199 continuous 8um-thick sections. Thefirst set of sections were stained with Hematoxyline & Eosin to measure the infarction and evaluate the effects of DCXW. The second set of sections were analyzed with the expression of VEGF by immunohistochemistry to evaluate effects of DCXW on VEGF expression. Results:Our results confirmed that the infarction area of permanent ischemic group is larger than that of transient ischemic group. With the treatment of DCXW, the infarction area was apparently reduced compared to the groups administered with saline, suggesting a positive effect of DCXW in protecting the cerebrum against ischemic damage. The expression of VEGF was up-regulated in both permanent and transient ischemic rats and rats treated with DCXW demonstrated by immunochemistry. Our results demonstrate that DCXW reduced the area of ischemia injury in cerebrum, probably by up-regulating the expression of VEGF in the periphery of ischemic region, which induces regeneration of blood vessels to improve the blood supply in ischemic regions.
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