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骨髓造血干细胞移植在大鼠肝纤维化模型中的定植及修复作用 被引量:1

Localization and therapeutic effect of bone marrow hematopoietic cell transplantation in rat model of liver fibrosis
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摘要 目的探讨骨髓造血干细胞(HSC)移植在四氯化碳(CCl4)导致大鼠肝纤维化模型中的定植及对肝损伤的修复作用。方法体外分离培养雄性SD大鼠骨髓HSC,移植前用5-溴-2-脱氧尿嘧啶(Brd U)标记HSC。将18只雌性SD大鼠随机分为A、B、C 3组,每组各6只。采用CCl4制作雌性大鼠肝纤维化模型,其中A组在注射CCl4的第4周,将含HSC的细胞悬液经尾静脉注入大鼠体内,B、C组采用相同方法注射生理盐水作为对照。至第8周抽取各组大鼠外周血样本,处死大鼠,取肝脏、胰腺及胃组织,检测HSC的定植情况,评估HSC对肝损伤的修复作用。采用双盲法统计实验结果。计量资料多组间比较采用方差分析,进一步两两比较采用SNK-q检验;计数资料多组间比较采用Kruskal-Wallis H检验,进一步两两比较采用Nemenyi法检验。结果 A组与B组相比,组织病理学明显好转,而A、C两组的组织学表现基本一致。A、B、C 3组间肝纤维化分级差异具有统计学意义(χ2=13.14,P=0.001),其中A、C两组肝纤维化分级均低于B组,差异均具有统计学意义(P值均<0.05);A组肝脏中均可检测到Brd U阳性细胞(100%),而胰腺、胃组织未检测到阳性细胞,B、C组均未检测到Brd U阳性细胞;A、C两组的ALT、AST水平均低于B组,白蛋白水平高于B组,差异均具有统计学意义(P值均<0.05)。结论同种异体HSC移植可在大鼠实验性肝纤维化模型中定植,并对受损肝脏具有修复作用。 Objective To investigate the localization and therapeutic effect of a11ogeneic bone marrow hematopoietic stem cell (HSC) trans- plantation in the rat model of liver fibrosis induced by carbon tetrachloride ( CCI4 ). Methods Bone marrow HSCs from allogeneic Sprague -Dawley (SD) rats were isolated and cultured in vitro and labeled with 5 -bromo -2' -deoxyuridine (BrdU) before transplantation. Eighteen female SD rats were randomly and equally divided into groups A, B, and C. A female rat model of liver fibrosis was established u- sing CC14. The rats in group A were injected with HSC - containing suspension through the caudal vein in the fourth week after CC14 injec- tion, while the rats in groups B and C were injected with normal saline through the caudal vein. In the eighth week, blood samples were taken from all groups. Then all rats were sacrificed, and the liver, pancreatic, and stomach tissues were collected to examine the localization of HSC and evaluate the therapeutic effect of HSC on liver damage. The double - blind method was used to statistically analyze experimental results. Comparison of continuous data between these groups was made by analysis of variance, and pa!rwise comparison was made by SNK - q test; comparison of categorical data between these groups was made by Kruskal - Wallis H test, and Pai rwise comparison was made by Nemenyi test. Results Group A showed significantly improved histopathology compared with group B, while groups A and C showed ap- proximately the same histological findings. There were significant differences in classification of liver fibrosis between groups A, B, and C (x^2 = 13. 14, P =0. 001 ) , and groups A and C had significantly lower grades of, liver fibrosis than group B (both P 〈0.05). In group A, BrdU - positive cells were detected in the liver tissues of all rats, but no positive cells were detected in the pancreatic and stomach tissues ; no BrdU -positive cells were detected in groups B and C. Compared with group B, groups A and C had significantly lower alanine aminotransferase and aspartate aminotransferase levels but a significantly higher albumin level ( all P 〈 0.05 ). Conclusion Allogeneic HSC can be localiged in the rat model of liver fibrosis and reverse the liver damage.
出处 《临床肝胆病杂志》 CAS 2015年第11期1878-1882,共5页 Journal of Clinical Hepatology
关键词 肝硬化 造血干细胞移植 大鼠 Sprague-Dawley liver cirrhosis hematopoietic stem cell transplantation rats, Sprague - Dawley
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