四氯化碳肝损伤模型中AMD3100对骨髓单个核细胞归巢的作用

Effect of AMD3100 on the bone marrow mononuclear cells homing to the injured liver of rat induced by carbon tetrachloride

目的用同种异体骨髓单个核细胞(BMMNC)与CXCR4特异性受体拮抗剂AMD3100孵育的BMMNC分别输注给四氯化碳构建的急性肝损伤SD大鼠,观察肝脏损伤修复作用,研究外源性骨髓单个核细胞是否通过SDF-1/CXCR4生物学轴归巢至受损肝脏。方法以四氯化碳作为肝脏毒剂,构建SD大鼠肝损伤模型。将SD大鼠随机分为4组:BMMNC移植(Ⅰ)组、AMD3100+BMMNC(Ⅱ)组、肝损伤对照(Ⅲ)组、正常健康SD大鼠(Ⅳ)组,每组各6只大鼠,III组腹腔注射50%四氯化碳(CCl4)花生油溶液,I组和II组经腹腔注射CCl424h后,分别经鼠尾静脉途径输入BMMNC和AMD3100孵育的BMMNC,正常健康SD大鼠不做任何处理,1周后,取血测定肝功能、计算死亡率及观察肝脏病理组织学表现。结果不同剂量的CCl4可导致不同程度的肝损伤,而0.45mL/100g剂量较好地模拟了急性肝损伤的病理生理改变且稳定性较好。移植后1周,I组大鼠死亡率约为17%,II组死亡率约为83%,2组死亡率比较差异有统计学意义(P<0.05),I组大鼠肝功能明显好于II和III组(P<0.05),同时肝脏的病理形态有所好转。结论 CCl40.45mL/100g腹腔注射可以很好构建SD大鼠急性肝损伤模型。BMMNC移植对大鼠急性肝损伤有一定的治疗作用,AMD3100对BMMNC向受损肝脏归巢有一定的抑制作用。

Objective To observe the effect of allogeneic bone marrow mononuclear cells transplantation on injured liver（BMMNC） and determine whether BMMNC could home to injured liver mediated by SDF-1/CXCR4.Methods Liver injury model induced carbon tetrachloride in SD rat was established.The rats were randomly divided into BMMNC transplantation group（group I） and,AMD3100 intervention group（group II）,the liver injury control group（group III）,and normal control group（group IV）.The rats in group I were injected with BMMNCs through tail vein.The rats in group II were injected with BMMNCs which were treated by specific receptor antagonist AMD3100 of CXCR4 through tail vein.One week after transplantation,liver function were tested in all rats.The mortality of rats in each group were calculated.The histological change of liver were observed in dead rats.Results （1） Different degrees of liver injury can be induced by different dosages of carbon tetrachloride,and the pathophysiology of acute liver injury can be copied steadily at the dose of 0.45ml/100g.（2） One week after transplantation,the mortality of group I and III were 17% and 83% respectively.There was significant difference between the two groups（P0.05）.The liver function of group I is better than that of group II and III.Conclusion（1） Acute liver injury can be induced in rats by carbon tetrachloride at the dose of 0.45ml/100g.（2）BMMNC transplantation could improve the acute liver injury of rats.AMD3100 could inhibit the BMMNC homing to the injured liver.