骨髓间充质干细胞调控尿激酶型纤溶酶原激活物表达及其对大鼠肝星状细胞凋亡的影响**

背景：骨髓间充质干细胞主要通过旁分泌及激活肝细胞生长因子促进肝星状细胞凋亡。 目的：观察骨髓间充质干细胞对尿激酶型纤溶酶原激活物合成的调控及肝细胞生长因子活性的影响,探讨其诱导肝星状细胞凋亡的机制。 方法：实验分为5组：①共培养组：大鼠骨髓间充质干细胞与肝星状细胞建立上下双层细胞共培养体系。②肝星状细胞单独培养组。③纤维原细胞对照组。④UK122干预组：在骨髓间充质干细胞与肝星状细胞共培养6 h前加入尿激酶型纤溶酶原激活物特异性抑制剂UK122。⑤骨髓间充质干细胞空白对照组。 结果与结论：共培养组尿激酶型纤溶酶原激活物mRNA表达较肝星状细胞单独培养明显增加(P < 0.01)。与肝星状细胞单独培养相比,共培养组的肝星状细胞在与骨髓间充质干细胞共培养24 h后表现明显增殖抑制(P < 0.01),且呈现时间依赖性;骨髓间充质干细胞与肝星状细胞共培养后,活性肝细胞生长因子的蛋白表达及肝星状细胞凋亡增加(P < 0.01)。UK122干预后活性肝细胞生长因子表达及肝星状细胞凋亡减少(P < 0.01)。提示骨髓间充质干细胞通过促进分泌尿激酶型纤溶酶原激活物,增加活性肝细胞生长因子表达,促进肝星状细胞凋亡。

Bone marrow mesenchymal stem cells increased expression of urokinase type plasminogen activator and promoted apoptosis of hepatic stellate cells in rats

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) promote the apoptosis of hepatic stellate cells (HSCs) by paracrine and activation of hepatocyte growth factor (HGF).  OBJECTIVE: To investigate the effects of BMSC regulation to urokinase type plasminogen activator on activity of hepatocyte growth factor, and the mechanism by which BMSCs induce the apoptosis of hepatic stellate cells. METHODS: Five groups were divided randomly: Co-culture group, in which rat BMSCs and HSCs were co-cultured by upper and down double-layer co-culture system; HSCs group, in which HSCs were simply cultured; fibroblasts group; UK122 pretreated group: 6 hours before co-culture of BMSCs and HSCs, urokinase type plasminogen activator specific inhibitor UK122 was added; BMSCs blank control group. RESULTS AND CONCLUSION: mRNA expression of urokinase type plasminogen activator in the co-culture group was significantly higher than in the HSCs group (P < 0.01). Compared with HSC group, HSC proliferation was significantly inhibited in the co-culture group at 24 hours (P < 0.01) in a time-dependent manner. After co-culture, HGF protein expression and HSC apoptosis were significantly increased (P < 0.01). After UK122 intervention, HGF expression and HSC apoptosis were significantly decreased (P < 0.01). These findings suggest that BMSCs promote the secretion of urokinase type plasminogen activator, increase the expression of active HGF, and promote the apoptosis of HSCs.