中华眼镜蛇毒因子清除补体建立异种心脏移植急性血管性排斥反应模型

Establishment of Discordant Cardiac Xenograft Acute Vascular Rejection Model by Depletion of Complement with Chinese Cobra Venom Factor

目的 采用纯化中华眼镜蛇毒因子 (CVF)清除补体 ,建立豚鼠 -大鼠非协调性异种心脏急性血管性排斥反应 (AVR)模型。 方法 供者豚鼠和受者 SD大鼠各 38只 ,分为 3组 : 组 (超急排组 ,n=2 0 ) ,受者不进行任何预处理 ; 组 (小剂量 CVF组 ,n=1 0 ) ,受者移植前 1 d经腹腔注射 CVF2 0 0 μg/ kg,移植后每日注射 1 0 0 μg/kg直至供心停搏 ; 组 (大剂量 CVF组 ,n=8) ,受者移植前 1 d经腹腔注射 CVF4 0 0 μg/ kg,移植后每日注射 2 0 0μg/ kg直至供心停搏。观察供心存活时间 ,供心停跳后行病理组织学检查。 结果 组和 组供心平均存活时间分别为 (4 1± 2 ) h和 (4 0± 3) h明显长于 组 [(1 7± 2 ) min,P<0 .0 1 ], 组与 组间差异无显著性 (P>0 .0 5 )。病理检查 : 组呈超急性排斥反应 (HAR)改变 ,而 、 组呈 AVR改变 ; 、 组移植物炎症细胞浸润数明显多于 组(P<0 .0 1 ) ,移植物补体 C3沉积明显少于 组 (P<0 .0 1 )。 结论 适当剂量纯化 CVF具有良好的清除大鼠补体C3作用 ,克服豚鼠—大鼠非协调性异种心脏移植物 HAR的发生 ,延长其存活时间 ,建立以炎症细胞浸润为主的异种移植

Objective To establish the xenograft acute vascular rejection(AVR) model of guinea pig to rat discordant cardiac xenografts by depletion of complement with purified Chinese cobra venom factor(CVF). Methods In a cervical heterotopic cardiac transplantation model by Cuff technique, guinea pig donors and SD rat recipients were divided into three groups: group Ⅰ(n=30), unpretreated recipients as control; group Ⅱ(n=10), recipients pretreated with low dose of CVF(200 μg/kg); group Ⅲ(n=8), recipients pretreated with high dose of CVF(400 μg/kg). The survival time of xenograft was measured and histopathologic observation was carried out after the graft arrested. Results CVF therapy had significantly prolonged xenograft average survival time(P<0 01). There was no significant difference between various dosages of CVF therapy(P>0 05). The histological changes of hyperacute rejection(HAR) were shown in group Ⅰand those changes of AVR were shown in other two groups. The numbers of inflammatory cell infiltration in cardiac xenografts of group Ⅱ and group Ⅲ were more than those of group Ⅰ(P<0 01), whereas the complement C 3 deposition on cardiac xenografts of group Ⅱ and group Ⅲ was less than those of groupⅠ(P<0 01). Conclusion An appropriate dosage of purified CVF administration showed excellent effects to deplete complement C 3 in rats and can prevent guinea pig to rat discordant cardiac xenografts from HAR, prolong the survival time. A xenograft AVR model with the characteristic of a mass of inflammatory cell infiltration was thus established.