MMP1过表达的骨髓间充质干细胞对肝纤维化的修复作用

目的：探讨基质金属蛋白酶1(matrix metalloproteinase 1，MMP-1)过表达的骨髓间充质干细胞(bone marrow
mesenchymal stem cells，BMSCs)对大鼠肝纤维化修复作用的影响。方法：50只雄性SD大鼠随机分为4组，重组腺病毒
Ad-人MMP-1(human MMP-1，hMMP-1)-增强绿色荧光蛋白(enhanced green fluorescent protein，EGFP)组(A组，n=10)、
空载体Ad-EGFP组(B组，n=10)、肝纤维化对照组(C组，n=15)及正常对照组(D组，n=15)。应用CCl4植物油溶液皮下
注射制作大鼠肝纤维化模型，10周后成模。经尾静脉将已转染的细胞注入大鼠体内，肝纤维化对照组和正常组注射
等量生理盐水。3周后处死大鼠，观察转染MMP-1的BMSCs对大鼠体质量、肝组织质量、肝功能、肝纤维化指标及
肝组织病理的影响。结果：与对照组相比，转染MMP-1的BMSCs致大鼠体质量、肝组织质量和血清白蛋白显著增加
(P<0.05)；血清谷丙转氨酶(ALT)、总胆红素(TBIL)、透明质酸酶(hyaluronic acid，HA)、层粘连蛋白(laminin，LN)及III
型前胶原(procollagen III，PC III)显著下降(P<0.05)；苏木精-伊红染色法(HE染色)可见平均视野下纤维化的程度显著改
善(P<0.05)。结论：转染hMMP-1能够增强BMSCs对肝纤维化的修复能力。

Therapeutic effect of BMSCs with over-expressed MMP1 on liver fibrosis

Objective: To investigate the function of bone marrow mesenchymal stem cells (BMSCs) with
over-expressed matrix metalloproteinase 1 (MMP1) on liver fibrosis.
Methods: Fifty SD male rats were randomly divided into 4 groups: recombinant adenovirus Adhuman
MMP-1(hMMP-1)-enhanced green fluorescent protein (EGFP) transfected BMSCs group
(Group A, n=10), Ad-EGFP transfected BMSCs group (Group B, n=10), liver fibrosis group
(Group C, n=15), and a normal group (Group D, n=15). The liver fibrosis model was formed by
subcutaneous injection of the mixed liquor of carbon tetrachloride (CCL4) and vegetable oil. After 10 weeks, the model of liver fibrosis was formed. Group A and B were administered the transfected
BMSCs via the tail veins, while Group C and D were administered normal saline. After 3 weeks,
the rats were sacrificed. The body weight, liver weight, liver function, liver fibrosis indexes and liver
pathological changes were tested.
Results: Compared with the control group, the rats administered BMSCs with over-expressed
MMP1 showed a significant improvement in the body weight, liver weight and plasma albumin
(ALB) (P<0.05), and a significant reduction in the plasma alanine aminotransferase, total bilirubin,
hyaluronic acid, laminin and procollagen III (P<0.05). Hematoxylin-eosin staining confirmed that
the degree of liver fibrosis was significantly ameliorated under average visual fields (P<0.05).
Conclusion: The repair ability of BMSCs on liver fibrosis can be enhanced by over-expression of
hMMP-1.