雌二醇对小鼠颈部移植心脏免疫耐受影响的初步研究

目的探讨雌二醇对小鼠颈部移植心脏免疫耐受的影响。方法建立小鼠颈部心脏异位移植模型,供、受体均为近交系健康雄性BALB/c和C57BL/6小鼠,分别在受体小鼠心脏移植术后1 d,3 d,7 d腹腔注射不同剂量外源性雌二醇实现干预。实验分为4组:A组:对照组,供、受体均无特殊处理;B组:2 mg/kg;C组:4 mg/kg;D组:6 mg/kg。术后观察比较各组受体小鼠供心存活时间、排斥反应程度及冠状动脉内膜增生程度。结果B、C、D组受体小鼠比A组存活天数明显延长(13.7±1.6)d、(15.3±1.9)d、(16.7±2.2)d与(8.8±1.3)d,P<0.05],B、C、D组之间相比,随着外源性雌二醇注射剂量的增加存活天数有所延长,但差异无统计学意义。切取移植后供心进行苏木精-伊红染色病理检查发现:术后第7天B、C、D组心肌组织间存在多灶型炎症细胞浸润并伴有部分心肌坏死,但是移植心发生排斥反应的程度轻于A组,术后第7天排斥分级显示D组移植小鼠明显较A组小鼠排斥反应轻。通过弹力纤维染色图像分析测定发现各组移植心脏冠状动脉内膜增厚程度随着存活天数的延长而加重,术后7 d给予B、C、D组冠状动脉内膜增生慢,且随着外源性雌二醇注射剂量的增加,冠状动脉内膜增生更慢。结论雌二醇干预能够抑制免疫排斥反应,减轻冠状动脉内膜增生,延长移植心脏存活时间,在诱导小鼠移植心脏产生免疫耐受方面具有一定作用。

Effect of estradiol on immune tolerance of mice with heart transplantation in the neck:a preliminary study

Objective To investigate the effect of estradiol on immune tolerance of mice with heart trans-plantation in the neck.Methods A mouse model of heterotopic heart transplantation in the neck was established using healthy inbred BALB/c and C57BL/6 male mice as the donor and recipient.At 1 d,3 d,and 7 d after heart transplantation,the recipient mice were injected intraperitoneally with different doses of exogenous estradiol as an intervention.The experiment was conducted with the mice divided into 4 groups,i.e.group A(control group,with no specific treatments for donors and recipients),group B(2 mg/kg estradiol),group C(4 mg/kg estradiol)and group D(6 mg/kg estradiol).The survival time,severity of rejection and coronary intimal hyperplasia in each group of recipient mice were observed and compared after surgery.Results The recipient mice in groups B,C,and D experienced significantly more survival days than those in group A(13.7±1.6)d,(15.3±1.9)d,(16.7±2.2)d vs(8.8±1.3)d,P<0.05).The comparison among groups B,C and D showed that higher injection dose of exogenous estradiol was associated with longer survival,but the difference was not statistically significant.The transplanted donor heart was then harvested for pathological study with HE staining.The findings showed that there was multi-focal inflammatory infiltrations and partial necrosis interspersing the myocardial tissues of mice in groups B,C,and D on day 7 after surgery,but the rejection of the transplanted heart in these groups was less severe than that in group A.Grading of rejection in recipient mice on day 7 after surgery showed that group D had significantly less rejection than group A.Image analysis with elastic fiber staining showed that the intimal thickening of coro-nary arteries in each group of transplanted hearts increased with survival days.The intimal hyperplasia in coronary arteries in groups B,C,and D was slow at 7 days after surgery,and was even slower along with increase in the injection dose of exogenous estradiol.Conclusion Estradiol intervention can suppress immune rejection,reduce coronary intimal hyperplasia,prolong the survival time of transplanted hearts,and thereby play a role in inducing immune tolerance of transplanted hearts in mice.