受体CX3CR1基因敲除对同种异系小鼠气管移植术后排斥反应的影响

Effect of CX3CR1 gene knockout on rejection of allogeneic mice after tracheal transplantation

目的探讨趋化因子受体CX3CR1基因敲除对同种异系小鼠气管移植后排斥反应的影响。方法将24只小鼠分为同系移植对照组、异系移植对照组、基因敲除移植组,每组各4对。基因敲除移植组、同系移植对照组受体和供体均为BABL/c小鼠;异系移植对照组供体为BABL/c小鼠,受体为C57BL/6小鼠;基因敲除移植组供体为BABL/c小鼠,受体为CX3CR1基因敲除小鼠。各组均行颈背部气管移植,每只受鼠移植2段气管。4周后取出各受鼠移植气管段,石蜡包埋,切片,HE染色,镜下观察管腔纤维化阻塞情况;采用ELISA法检测受鼠血清高迁移率族蛋白1(HMGB1)水平。结果同系移植对照组8个移植气管段均无管腔阻塞,阻塞分数为0;异系移植对照8个移植气管段均出现管腔阻塞,移植气管管腔内充满黏液,镜下见管腔内有大量增生的成纤维细胞,阻塞分数为8.0;受体敲除移植组8个移植气管段中1个出现管腔受挤压、扭曲,1个阻塞不明显,其余6个均未出现较明显的管腔纤维化阻塞,移植气管管腔内充满黏液,镜下见管腔内有大量增生的成纤维细胞,阻塞分数为0.96。移植后4周同系移植对照组、异系移植对照组、基因敲除移植组血清HMGB1水平分别为(29.8±1.6)、(83.6±1.4)、(19.8±0.9)ng/mL,基因敲除移植组明显低于异系移植对照组(P<0.05),但与同系移植对照组比较,P>0.05。结论受体CX3CR1基因敲除可明显减轻气管移植后排斥反应。

Objective To investigate the effect of chemokine receptor CX 3CR1 gene knockout on rejection of alloge-neic mice after tracheal transplantation .Methods Twenty-four mice were divided into three groups： homologous control group, allogenic control group , and gene knockout transplantation group with 4 pairs in each.In the homologous control group, all donor mice and recipient mice were BALB/c mice.In the allogenic control group , donor mice were BALB/c mice, and recipient mice were C57BL/6 male mice.In the gene knockout transplantation group , donor mice were BALB/c mice, and recipient mice were CX3CR1 knockout mice （C57BL/6 background）.Trancheal transplantation operation was performed in all groups , and each recipient mouse was transplanted with 2 tracheas.At week 4 after transplantation , the tracheal grafts were removed and the pathological change was detected with HE staining .Meanwhile, the serum high-mobil-ity group box 1 protein （HMGB1） levels in the recipients of each group were detected with ELISA .Results HE staining showed that there was no fibrosis in the tracheal grafts from the homologous control group , and the blocking score was 0.All tracheal grafts from the allogenic control group had fibrosis , and the blocking score was 8.0.In the gene knockout trans-plantation group, 1 tracheal graft had fibrosis, and the blocking score was only 0.96.At week 4 after transplantation, the HMGB1 levels in the homologous control group , allogenic control group , and gene knockout transplantation group were （29.8 ±1.6）, （83.6 ±1.4）, and （19.8 ±0.9） ng/mL, and the HMGB1 level was lower in the gene knockout trans-plantation group than in the allogenic control group （P＆lt;0.05）, but no significantly difference was found between the ho-mologous control group and the gene knockout transplantation group （P＆gt;0.05）.Conclusion Receptor CX3CR1 knock-out can significantly reduce the rejection after tracheal transplantation .