经门静脉注射骨髓间充质干细胞对大鼠转化生长因子-βR1、-βR2的影响  

Effect of bone marrow mesenchymal stem cells via portal vein injection on transforming growth factor-βR1 and-βR2 in rats with acute liver failure

作　　者：徐土炳 李莉 母汉正 罗兴迪 帅领[3] 张玉君[3] 

机构地区：[1]解放军第十六医院普外科,新疆阿勒泰836500 [2]解放军第十六医院医务处,新疆阿勒泰836500 [3]第三军医大学附属西南医院全军肝胆外科研究所,重庆400038

出　　处：《中国普外基础与临床杂志》2017年第8期953-957,共5页Chinese Journal of Bases and Clinics In General Surgery

摘　　要：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。[Abstract] Objective To investigate effect ot bone marrow li ： injection on transforming growth factor-[~ receptor 1 （TGF-~R1） and TGF-~R2 in rats with acute liver failure （ALF）. Methods Sixty male SD rats were randomly divided into a normal control group, ALF model group, and BMSCs treatment group, with 20 rats in each group. The rats of normal control group were directly sacrificed without other treatment. The ALF models were made in the rats of BMSCs treatment group and ALF model group, then were treated with BMSCs and equal volume of normal saline respectively. On day 7 after treatment, the 1-week survival situation of rats was observed, the pathological change was observed by HE staining, the apoptosis of liver cells was detected by TUNEL method, and the TGF-βR1 and TGF-βR2 proteins expressions were detected by Western blot method. Results ① The 1-week survival rate of the BMSCs treatment group was significantly higher than that of the ALF model group （P〈0.05）.② In the ALF model group, the liver cells were diffuse necrosis, the lobular structure was indistinct, and a large number of bridging necrosis. In the BMSCs treatment group, the infiltrations of inflammatory cells were decreased, and the structure of hepatic lobules gradually recovered, and the normal hepatocytes were seen around it. ③ The apoptosis indexes of the BMSCs treatment group and the ALF model group were significantly higher than those in the normal control group （P〈0.05）, which in the BMSCs treatment group was significantly lower than that of the ALF model group （P〈0.05）. ④ The TGF-ββR1 and TGF-R2 proteins expressions in the liver tissues of the ALF model group were significantly higher than those of the normal control group （P〈0.05）, which of the BMSCs treatment group were significantly lower than those of the ALF model group （P〈0.05）. Conclusion BMSCs could inhibit apoptosis ofhepatocytes in ALF. Its mechanism might be related to expressions of TGF-βR1 and TGF-βR1 proteins, but its spe

关 键 词：骨髓间充质干细胞 转化生长因子-β受体1 转化生长因子-β受体2 急性肝功能衰竭 大鼠 

分 类 号：R575.3[医药卫生—消化系统]