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目的探讨经门静脉注射骨髓间充质干细胞对急性肝功能衰竭大鼠肝脏组织中转化生长因子-β受体(TGF-βR)1和TGF-βR2的影响。方法选择清洁级雄性SD大鼠60只,随机分为正常对照组、急性肝功能衰竭组和骨髓间充质干细胞治疗组,每组20只大鼠。正常对照组不给予任何处理。急性肝功能衰竭组和骨髓间充质干细胞治疗组大鼠均先制备急性肝功能衰竭模型,然后骨髓间充质干细胞治疗组经门静脉注射骨髓间充质干细胞,急性肝功能衰竭组给予等体积的生理盐水。治疗后第7天,观察各组大鼠的存活情况,采用HE染色法观察各组大鼠肝脏组织的病理学变化,TUNEL法检测各组大鼠的肝细胞凋亡情况,Western blot法检测各组大鼠肝脏组织中TGF-βR1和TGF-βR2蛋白表达情况。结果 (1)急性肝功能衰竭组术后1周存活率明显低于正常对照组(P<0.05),骨髓间充质干细胞治疗组术后1周存活率明显高于急性肝功能衰竭组(P<0.05)。(2)急性肝功能衰竭组的肝细胞呈弥漫性坏死,小叶结构模糊不清,见大量桥接样坏死;骨髓间充质干细胞治疗组炎性细胞浸润减少,肝小叶结构逐渐恢复,周围可见正常肝细胞。(3)急性肝功能衰竭组和骨髓间充质干细胞治疗组肝细胞凋亡指数均明显高于正常对照组(P<0.05),而骨髓间充质干细胞治疗组的细胞凋亡指数较急性肝功能衰竭组明显降低(P<0.05)。(4)急性肝功能衰竭组的肝脏组织中TGF-βR1和TGF-βR2蛋白相对表达量明显高于正常对照组(P<0.05);骨髓间充质干细胞治疗组的肝脏组织中TGF-βR1和TGF-βR2蛋白相对表达量较急性肝功能衰竭组明显降低(P<0.05)。结论骨髓间充质干细胞在肝细胞损伤恢复中能抑制肝细胞凋亡,其机制可能与调节TGF-βR1和TGF-βR2蛋白的表达有关,但其具体调节通路需要进一步的研究。
Objective To investigate the effects of transplanting bone marrow mesenchymal stem cells (BMSCs) into the liver of rats with acute hepatic failure on the expression of transforming growth factor-β receptor (TGF-βR) 1 and TGF-βR2 via portal vein. Methods Sixty clean male Sprague Dawley rats were randomly divided into normal control group, acute liver failure group and bone marrow mesenchymal stem cell treatment group, 20 rats in each group. The normal control group did not receive any treatment. Acute hepatic failure group and BMSC-treated group were prepared acute liver failure model, then bone marrow mesenchymal stem cells treated group by intravenous injection of bone marrow mesenchymal stem cells, acute liver failure group given equal volume Physiological saline. On the 7th day after treatment, the survival of the rats in each group was observed. The pathological changes of the liver tissues in each group were observed by HE staining. The apoptosis of hepatocytes in each group was detected by TUNEL method. The expression of TGF-βR1 and TGF-βR2 in the liver tissue of rats. Results (1) The survival rate of 1-week post-operation in acute liver failure group was significantly lower than that in normal control group (P <0.05). The survival rate of bone marrow-derived mesenchymal stem cell group was significantly higher than that of acute liver failure group <0.05). (2) Acute liver failure group showed diffuse necrosis of hepatocytes, vague lobular structure, a large number of bridge-like necrosis; decreased inflammatory cell infiltration in the bone marrow-derived mesenchymal stem cells group, hepatic lobule structure gradually restored around the normal Hepatocyte. (3) Apoptosis index of hepatocytes in acute liver failure group and BMSC group were significantly higher than that of normal control group (P <0.05), while the apoptosis index of BMSC treated group was higher than that of acute liver Fibrosis group was significantly lower (P <0.05). (4) The relative expression of TGF-βR1 and TGF-βR2 in the liver tissue of acute liver failure group was significantly higher than that of the normal control group (P <0.05); The expression of TGF-βR1 and The relative expression of TGF-βR2 protein was significantly lower than that of acute liver failure group (P <0.05). Conclusion Bone marrow mesenchymal stem cells can inhibit the apoptosis of hepatocytes during the injury of hepatocytes. The mechanism may be related to the regulation of the expression of TGF-βR1 and TGF-βR2, but the specific regulation of BMSCs requires further study.