青蒿琥酯对大鼠小肠移植急性排斥反应的作用

背景：随着强效、特异免疫抑制剂的问世，小肠移植的成活率有了一定程度的提高。但这些免疫抑制剂的不良反应及昂贵的治疗费用，让很多患者难以承受。所以，选择有免疫抑制作用的中药在临床上应用是很有意义的。青蒿琥酯有免疫抑制作用，可以减轻小肠移植急性排斥反应，提高小肠移植的成功率。 目的：观察青蒿琥酯在大鼠小肠移植急性排斥反应中的作用及其机制。方法：选用封闭群SD大鼠和Wistar大鼠建立同种异基因小肠移植模型，随机分为3组：①同基因移植组（SD→SD）。②异基因移植组（Wistar→SD）。③异基因移植＋青蒿琥酯治疗组（Wistar→SD＋青蒿琥酯60 mg/（kg？d），腹腔注射）。〈br〉 结果与结论：同基因移植组大鼠存活均超过10 d，并于第10天全部处死。异基因移植组大鼠平均存活（6.7±0.58） d，治疗组大鼠平均存活（8.50±0.74） d，两组间比较差异有显著性意义（P＜0.01）。病理组织学检查显示同基因移植组标本无明显排斥征象，异基因移植组标本在术后第3，5，7天分别符合轻、中、重度排斥反应，治疗组部分标本有轻度排斥表现，但出现较晚、程度较轻。ELISA 法检测显示异基因移植组血清白细胞介素2、γ-干扰素表达水平在术后均显著高于其他2组（P＜0.01），治疗组血清白细胞介素2表达水平与同基因移植组比较亦有升高，但差异无显著性意义（P＞0.05），治疗组血清γ-干扰素表达水平高于同基因移植组（P＜0.05）。结果可见青蒿琥酯对大鼠小肠移植急性排斥反应有抑制作用，其作用机制可能与抑制白细胞介素2、γ-干扰素等细胞因子的分泌表达有关。

Effect of artesunate on acute rejection after small intestine transplantation in rats

BACKGROUND：As the potent, specific immunosuppressants emerge, the survival rate after intestinal transplantation is improved to some extent. However, the adverse effects of immunosuppressants and expensive treatment costs are not tolerable for many patients. Therefore, it is clinical y meaningful to choose traditional Chinese medicine which presents immunosuppressive effects. Artesunate has immune suppression effect, reduces acute rejection fol owing smal intestine transplantation, and improves the success rate of smal intestine transplantation. OBJECTIVE：To observe the effect and action mechanism of artesunate in acute rejection after smal intestine transplantation in rats. METHODS：Al ogeneic smal intestine transplantation models were established in the closed group of Sprague-Dawley rats and Wistar rats, and then were randomly divided into three groups, syngenic transplantation group （SD→SD）, al ogeneic transplantation group （Wistar→SD）, and artesunate treatment group （Wistar→SD＋artesunate 60 mg/kg per day, intraperitoneal injection）. 〈br〉 RESULTS AND CONCLUSION：Rats in syngenic transplantation group survived for more than 10 days and they were al kil ed on day 10. The average survival of rats in al ogeneic transplantation group and artesunate treatment group was respectively （6.73±0.58） days and （8.50±0.74） days, with significant differences between the two groups （P〈0.01）. Histopathological examination showed that, there was no apparent rejection in syngenic transplantation group specimens, but mild, moderate and severe rejections in al ogeneic transplantation group on days 3, 5, 7. In treatment group, some specimens had mild rejection, but appeared relatively late to a low degree. Enzyme linked immunosorbent assay results revealed that, serum interleukin-2 and interferon-gamma expression levels in al ogeneic transplantation group were significantly higher than other two groups after surgery （P〈0.01）, serum interleukin-2 gene expression level in treatment group was also higher than syngenic transplantation group, but there was no significant difference （P〉0.05）, serum interferon-gamma expression level in treatment group was higher than syngenic transplantation group （P〈0.05）. Artesunate can inhibit acute rejection after rat smal intestine transplantation, and its mechanism may be related to inhibition effect on the secretion and expression of interleukin-2, interferon-gamma and other cytokines.