骨髓间充质干细胞移植对大鼠肝纤维化的作用

目的探讨骨髓间充质干细胞（MSCs）移植在大鼠肝纤维化形成过程中的作用。方法应用密度梯度离心结合贴壁培养法分离纯化雄性SD大鼠MSCs，分别在四氯化碳诱导大鼠肝纤维化模型的第1天、第6周、第8周以5×10^6的剂量经尾静脉注入同种雌性大鼠体内。各组大鼠均在MSCs移植4周后，评价干预组与对照组的生存状态，并用Scheuer炎症活动度评分法和SchmidM纤维化评分法评价肝脏病理情况。结果第1天移植MSCs，干预组12只大鼠中有6只肝脏炎症活动度评分≤1分，对照组11只中仅有1只，两组Scheuer评分均值分别为1．50和2．55（t=2．894，P=0．009）；SchmidM评分均值分别为0．75和0．82（t=0．217，P=0．83）。第6周移植MSCs，干预组和对照组在炎症活动度方面无明显差异，Scheuer评分均值分别为3．58和3．73（P=0．559）；在纤维化方面，干预组12只大鼠中有3只≥6分，对照组11只中则有7只≥6分，SchmidM评分均值分别为4．75和5．54（t=2．424，P=0．024）；干预组与对照组的腹水发生率分别为25％和45．4％（t=2．241，P=0．036）。第8周移植MSCs，干预组与对照组炎症活动、纤维化程度及腹水发生率均无明显差异，Scheuer评分的均值分别为3．64和3．92（P=0．113）；SchmidM评分均值分别为5．27和5．67（t=1．207，P=0．241）；腹水发生率分别为18．2％和25％（t=0．703，P=0．490）。值得注意的是，对照组有5／12出现异形细胞，而干预组未见一例。结论早期移植MSCs可减轻四氧化碳引起的肝脏炎症，改善大鼠的肝纤维化程度，但对肝硬化无作用，MSCs移植可以减少肝硬化大鼠异形细胞发生的现象值得进一步探讨。

The effects of transplantation of mesenchymal stem cells on hepatic fibrogenesis in rats

Objeetive To investigate the effects of mesenchymal stem cells （MSCs） transplant ation on the development of hepatic fibrogenesis in rats. Methods MSCs from male SD rat were isolated and purified by density gradient centrifugation. The forth passage cells （5 × 10^6 ml）, expanded by subculture, were respectively injected into the homogeneous female rats via the caudalis vena on the first day, the sixth week and the eighth week during the hepatic fibrosis model induced by carbon tetrachloride（CCl4 ） in rats. Four weeks after MSC transplantation, the living state of rats and pathology of the liver in transplanted and control groups were evaluated by Scheuer inflammation activity score and Schmid M fibrosis grading score. Results 6 rats in 1^st day transplantation group（n = 12） were found that Scheuer inflammation activety grade less than point 1, while only one rat less than point 1 in control group（n=11）. The mean value of Scheuer inflammation score in transplantation group was 1.50, and 2. 55 in control group （t= 2.894, P= 0. 009）. The mean value of Schmid M Score in transplan- tation group was 0. 75, and 0.82 in control group （t=2. 894, P= 0. 009）. On 6th week of MSCs transplantation, no difference in inflammation activity grade was found in both groups. The mean value of Scheuer inflammation score was 3. 58 and 3.73, respectively （P=. 559）. While the mean value of Schmid M fibrosis score was 4. 75 in the transplantation group and 5. 54 in control group （t= 2. 424, P= 0. 024）. The ascites formation rate in transplantation group and control group was 25% and 45. 4% respectively（t = 2. 241 ,P = 0. 036）. On 8th week of MSCs transplantation there was no significant difference in inflammation activity grade, fibrosis stage and ascites formation rate between the two groups. The mean value of Scheuer inflammation score in transplantation group was 3.64, and 3.92 in control group （P= 0. 113）. The mean value of Schmid M score in transplantation group was 5.27, and 5.67 in contr