Protection Of Sodium Aescinate On Focal Cerebral Ischemia

Objective: 1. Sodium aescinate is a triterpene saponin derived from dry fruit of traditional Chinese medicine-poloze. This escin possesses anti-inflammatory, anti-exudtion, and anti-oxygen free radical. We observed the change of infarction volume and neurological deficit score in rats treated with sodium aescinate, using a rat ischemia/reperfusion model.2. In this study we investigated the effect of sodium aescinate on activation of NF-κB and apoptosis in transient focal cerebral ischemia rats.3. The purpose of present study is to investigate the effect of sodium aescinate on inflammation in focal ischemia, by contrasting the number of microglia and neutrophil and ICAM-1 positive microvascular in different treated-groups.4. The purpose of clinic study is to investigate the significance of serum IL-6, IL-8, TNF-(, IL-1( levels in patients with acute cerebral infarction, and the relationship between serum level of IL-6 and infarct volume and neurological deficit.Methods:1. Healthy male SD rats were randomly divided into three groups: sham-operated, sodium aescinate treated and saline treated. The left MCA of rats in treated groups was subjected to occlusion for 2h and reperfusion for 22h, using an intraluminal vascular occlusion method. Neurological abnormalities were evaluated using the scale described by Zea longa. Cut off the heads of the rats to get the brain. To estimate the brain ischemic damage, we stained the section of the optic chiasma brain in TTC, calculated the infarct size at the coronal level of the rostral edge of the optic chiasm by image analysis. DNA fragmentation was measured in adjacent paraffin sections with the use of a terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) method. The inmmunhistochemiscal stain of NF-κB p65 was also done in adjacent paraffin sections and the results were evaluated by positive cell numbers and intensity. ICAM-1 and MPO inmmunhistochemiscal stains were as well done in adjacent paraffin sections to detect the changes of vascular and neutrophil.2. Thirty-four patients within six hours after stroke were enrolled in this study. According to the size of infarct these patients were divided into large-infarct group (S≥3cm2) and small-infarct group (S≤1.5cm2), while according to different treatment these patients were divided into common-treated groups and sodium aescinate-treated groups. The neurological deficit score of all these patients were also evaluated. We also randomly chose 10 healthy men as control groups. Serum levels of IL-6, IL-8, TNF-( and IL-1( in 34 patients and 10 healthy subjects were measured by ELISA method.Results: 1. Intraperitoneal injection of sodium aescinate (5mg/kg) immediately after reperfusion ameliorated neurological dysfunction (P<0.01). Also the infarction was significantly smaller in sodium aescinate-treated rats (P<0.01).2. As contrasted with the saline-treated rats apoptotic cells were dramatically reduced in rats treated with sodium aescinate (P<0.01). The quantities of NF-κBp65 positive cells and the intensive of the stain were more in the saline control than the sodium aescinate treated ones.3. The numbers of MPO positive cells in ischemia hemisphere of sodium aescinate-treated groups was fewer than the saline control group (P<0.01). The proliferation of microglias was lighter in the sodium aescinate treated rats (P<0.01). Although the number of ICAM-1 positive vascular was fewer in sodium aescinate treated group, there had no significant statistical difference in treated groups and control groups (P>0.01). 4. As contrasted with serum levels of TNF-( and IL-1(, which did not exhibit a significant response, Serum levels of IL-6 showed a significant increase within 6 hours following the onset of stroke and reached a plateau period at 24h-36h, which returned to baseline by day 7. Serum levels of IL-6 in patients with large lesion were higher than those with small lesion (6h, P<0.01；24-36h, P<0.05). There was positive correlation between serum levels of...