c-Kit^+Lin^-细胞移植改善急性肝损伤的实验研究

The study of transplantation of c-Kit^+Lin^- cell for treatment of acute liver injure

目的探讨骨髓c-Kit+Lin-(CD117)细胞移植治疗小鼠急性肝损伤的效果以及机制,为骨髓源性肝干细胞的临床应用提供实验依据。方法 18只成年BALB/c小鼠随机分为正常组、实验组和干细胞移植组,正常组不予任何处理,模型组小鼠腹腔注射CCl4后仅输入生理盐水,移植组小鼠在腹腔注射CCl4后尾静脉输注骨髓CD117细胞(1×106),48 h后观察各组小鼠肝功能水平变化,苏木素-伊红(hematoxylin-eosin,HE)染色分析肝脏病理学改变,免疫组化检测肝脏细胞增殖情况。结果模型组腹腔注射CCl4后肝功能严重受损,血清谷丙转氨酶(alanine transaminase,ALT)、谷草转氨酶(glutamic oxalacetic transaminase,AST)、胆红素(bilirubin)等升高,肝脏的HE染色可见片状坏死,炎症细胞浸润;移植组小鼠移植干细胞48 h后小鼠肝功能有所恢复,病理提示肝脏坏死区域有所减小,Ki67免疫组化提示干细胞可促进肝脏再生。结论经尾静脉注入的骨髓来源的CD117干细胞能改善急性肝损伤肝功能以及修复受损肝脏,是治疗急性肝损伤的一种安全有效的方法。

Objective To investigate the effects of bone marrow c-Kit^＋Lin^-cell（CD117） transplantation on acute liver injury mice model and provide experimental basis for clinical application. Methods18 BALB / c mice were randomly divided into 3 groups： normal group, experiment group and stem cell transplantation group. In normal group, the mice did not give any processing. In experiment group, the CCl4 was injected intraperitoneally, and then infused saline. In stem cell transplantation group, the mice injected bone marrow CD117 cell（1 ×106） via tail vein after CCL4 intraperitoneal injection. The liver functional was measured after 48 hours. The liver histologic changes were assessed by hematoxylin-eosin（HE） staining. The hepatocyte proliferation was assessed by immunohistochemical. Results The liver functional of experiment group was severely damaged after CCL4 intraperitoneal injection.The expressions of alanine transaminase（ALT）, glutamic oxalacetic transaminase（AST） and bilirubin in experiment group increased. The HE staining revealed extensive hepatocellular necrosis in mice subjected to CCL4 intraperitoneal injection. In stem cell transplantation group.The liver function was recovered after 48 h of stem cell transplantation, and the area of necrosis was significantly lower. The Ki67 expressions indicated the stem cell can improve hepatocyte proliferation. Conclusion Inject bone marrow CD117 cell via tail vein can protect the liver from acute liver injury and repair the damaged liver. It can be considered as a therapeutic option to prevent acute liver injury.