重组人补体受体1型SCR15-18片段对肠缺血再灌注损伤的保护作用

Protective effect of recombinant SCR15-18 domain of human complement receptor type 1 on intestinal ischemia and reperfusion injury

目的:探讨人补体受体1型功能域SCR15-18(CR1-SCR15-18)对大鼠肠缺血再灌注损伤的保护作用。方法:SD大鼠随机分为假手术组(SO)、缺血再灌注组(I/R)和CR1-SCR15-18保护组(CR1)。结扎肠系膜上动脉30 min,再灌注60 min,建立小肠缺血再灌注模型,再灌注前5 min注射CR1-SCR15-18蛋白(30 mg/kg)。测定肠黏膜血管的通透性、组织髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量;HE染色观察小肠病理改变并根据Chiu's方法评分;免疫组织化学法检测补体C3组分的沉积。结果:与SO组相比,I/R组通透性增加,MPO活性和MDA含量显著升高,而SOD活性降低,肠黏膜病理损伤严重且有大量补体C3组分沉积。与I/R组相比,CR1组肠黏膜血管通透性显著降低,MPO活性和MDA含量显著降低,而SOD活性升高,肠黏膜损伤明显减轻,只有少量补体C3组分沉积。结论:CR1-SCR15-18蛋白抑制肠缺血再灌注时补体的活化,减轻肠组织损伤。

AIM：To investigate the protective effect of recombinant SCR15-18 domain of human complement receptor type 1（CR1-SCR-15-18） on intestinal ischemia and reperfusion in a rat model.METHODS： Sprague-Dawley rats were randomly divided into 3 groups： sham operation（SO） group,ischemia and reperfusion（I/R） group and CR1-SCR15-18 treatment group.The superior mesenteric artery of the rats was clamped for 30 min followed by 60 min of reperfusion.PBS alone or CR1-SCR15-18 protein（30 mg/kg） in PBS was intravenously administered 5 min before reperfusion.Intestinal vascular permeability,myeloperoxidase（MPO）,malondialdehyde（MDA） and superoxide dismutase（SOD） were measured.The histopathological changes of intestinal mucosa were examined by HE staining and complement 3 was detected by immunohistochemical analysis.RESULTS： Compared with SO group,the vascular permeability,the activity of MPO and the content of MDA in I/R group were significantly increased,and the activity of SOD was decreased.HE staining demonstrated that I/R induced severe intestinal histological damages and the increased amount of complement 3 and its derivates were deposited in the necrosis area.Compared with I/R group,the vascular permeability,the activity of MPO and the content of MDA were decreased and the activity of SOD was significantly increased in CR1-SCR15-18 treatment group.CR1-SCR15-18 also significantly attenuated intestinal histological injury,and reduced the deposition of complement 3 and its derivates in the necrosis zone.CONCLUSION： sCR1-SCR15-18 protein exerts a protective effect against intestinal I/R injury in rats,possibly by inhibiting the activation of complement.