摘要
目的观察埃他卡林对在体大鼠肾脏缺血再灌注损伤的影响,并初步探讨其作用机制。方法夹闭大鼠左侧肾动、静脉45 min再放开恢复血流24 h,造成急性缺血再灌注肾损伤模型(2周前已切除右肾);再灌注前3 d及缺血前1 h以埃他卡林溶液灌胃;应用放免法检测血清内皮素(ET)-1水平,应用RT-PCR法观察ET-1 mRNA在肾组织的表达。结果缺血再灌注导致明显的肾脏功能与结构损伤。组织病理示肾小管上皮细胞变性,核浓缩、破碎,刷状缘坏死脱落,管腔内有细胞及蛋白管型,间质充血、水肿;血清ET-1水平升高,肾组织ET-1 mRNA表达升高。与缺血再灌注组比较,埃他卡林能明显降低血清尿素氮和肌酐水平,改善上述病理变化,降低血清ET-1水平,降低肾组织ET-1 mRNA的高表达。结论埃他卡林对大鼠肾脏缺血再灌注损伤具有明显的保护作用。
Objective To study the protection and mechanism of iptakalim hydrochloride （ Ipt ） on ischemia-reperfusion（I/R） injury in the kidneys of rats. Methods On the 15th day following right nephrectomy, under anesthesia, a latero-abdominal laparotomy was made, and using minimal dissection, the left renal pedicle was isolated. The left renal pedicle was occluded for 45 min to induce ischemia and then subjected for 24 h of reperfusion to make I/R induced renal injury model. Ipt was orally gavaged at the doses of 0. 5,1.0,1.5 and 2.0 mg·kg^-1·d^ - 1 for 3 d and 1 h before ischemia. The concentration of serum endothelin-1 （ET-1） was evaluated by radioimmunoassay, the expression of ET-1 mRNA in the kidneys of rats was detected by RT-PCR. Results I/R injury caused a significant deterioration in the renal function, pretreatment with Ipt significantly improved the functional and histological parameters, decreased the concentration of ET-1 and inhibited the expression of ET-1 mRNA in kidneys induced by renal I/R injury. Conclusion Ipt has a protective effect on renal I/R injury in rats.
出处
《国际药学研究杂志》
CAS
2008年第2期81-86,共6页
Journal of International Pharmaceutical Research
基金
国家高技术研究发展计划(863计划)重大专项基金资助项目(No.2002AA2Z3137)
