CAJ | 학술논문

背景：肝硬化是多种原因引起的肝脏慢性病变，目前尚没有有效的治疗方法，很多研究表明，间充质干细胞对肝纤维化及肝硬化有一定的治疗作用。目的：研究人脐带源间充质干细胞移植对大鼠肝纤维化及肝硬化的治疗作用及其作用机制。方法：应用CCl4诱导制备肝纤维化及肝硬化模型，造模后经尾静脉注射人脐带间充质干细胞。细胞移植后采用Beckman Coulter analyzer检测人脐带源间充质干细胞移植对大鼠肝功能的影响；采用天狼猩红染色检测肝组织病理改变；应用免疫组织化学染色、Western blot和real-time Q-PCR方法检测Ⅰ、Ⅲ型胶原、基质金属蛋白酶2、基质金属蛋白酶抑制剂2蛋白与mRNA在大鼠肝组织中的表达。结果与结论：人脐带源间充质干细胞移植可以改善肝纤维化及肝硬化大鼠的肝功能。人脐带源间充质干细胞移植后，除肝纤维化细胞移植1周组与对应模型组相比差异无显著性意义外，其余各细胞移植组肝脏组织中基质金属蛋白酶2 mRNA及蛋白表达水平明显升高，而Ⅰ、Ⅲ型胶原、基质金属蛋白酶抑制剂2表达水平明显降低。人脐带源间充质干细胞通过上调基质金属蛋白酶2表达，下调基质金属蛋白酶抑制剂2表达，对肝纤维化及肝硬化起到治疗作用；在致病因素持续存在的情况下，人脐带源间充质干细胞移植并不能逆转肝纤维化或者肝硬化，只能延缓肝纤维化或肝硬化的进程。
배경：간경화시다충원인인기적간장만성병변，목전상몰유유효적치료방법，흔다연구표명，간충질간세포대간섬유화급간경화유일정적치료작용。목적：연구인제대원간충질간세포이식대대서간섬유화급간경화적치료작용급기작용궤제。방법：응용CCl4유도제비간섬유화급간경화모형，조모후경미정맥주사인제대간충질간세포。세포이식후채용Beckman Coulter analyzer검측인제대원간충질간세포이식대대서간공능적영향；채용천랑성홍염색검측간조직병리개변；응용면역조직화학염색、Western blot화real-time Q-PCR방법검측Ⅰ、Ⅲ형효원、기질금속단백매2、기질금속단백매억제제2단백여mRNA재대서간조직중적표체。결과여결론：인제대원간충질간세포이식가이개선간섬유화급간경화대서적간공능。인제대원간충질간세포이식후，제간섬유화세포이식1주조여대응모형조상비차이무현저성의의외，기여각세포이식조간장조직중기질금속단백매2 mRNA급단백표체수평명현승고，이Ⅰ、Ⅲ형효원、기질금속단백매억제제2표체수평명현강저。인제대원간충질간세포통과상조기질금속단백매2표체，하조기질금속단백매억제제2표체，대간섬유화급간경화기도치료작용；재치병인소지속존재적정황하，인제대원간충질간세포이식병불능역전간섬유화혹자간경화，지능연완간섬유화혹간경화적진정。
BACKGROUND:Cirrhosis is a long-term consequence of chronic hepatic injury, which has no effective therapy. Mesenchymal stem cels have been shown to play a potential role in the treatment of liver fibrosis/cirrhosis. OBJECTIVE:To investigate the therapeutic effect and mechanism of human umbilical cord-derived mesenchymal stem cels on CCl4 induced liver fibrosis/cirrhosis in rats. METHODS:A CCl4-induced liver fibrotic/cirrhotic rat model was used, and human umbilical cord-derived mesenchymal stem cels were injectedvia the tail vein after modeling. Liver biochemical profile was measured by Beckman Coulter analyzer. Histopathological changes were assessed by Sirius red staining. The expressions of colagen type I, colagen type III, matrix metaloproteinases-2 and tissue inhibitor of matrix metaloproteinases-2 protein and mRNA in liver tissues were observed by immunohistochemistry, western blot and real-time PCR, respectively. RESULTS AND CONCLUSION:Liver biochemical profile indicated the transplantation of human umbilical cord-derived mesenchymal stem cels could improve the liver function of rats with liver fibrosis and cirrhosis. After cel transplantation, except 1-week cel transplantation group, the expressions of the matrix metaloproteinases-2 mRNA and protein were significantly increased, while the expressions of colagen type I, colagen type III and tissue inhibitor of matrix metaloproteinases-2 mRNA and protein significantly decreased, compared with the corresponding model groups. Human umbilical cord-derived mesenchymal stem cels play a role in the treatment of liver fibrosis and cirrhosis through upregulating the expression of matrix metaloproteinases-2 and lowering the expression of inhibitor of matrix metaloproteinases-2. With the continued presence of pathogenic factors, human umbilical cord-derived mesenchymal stem cel transplantation cannot reverse liver fibrosis or cirrhosis, and only delay the process of liver fibrosis or cirrhosis.