脂肪间质干细胞移植对大鼠肝硬化模型的治疗作用

Therapeutic effect of adipose tissue-derived mesenchymal stem cells transplantation for rat model of hepatic cirrhosis

目的:探讨脂肪间质干细胞经门静脉及尾静脉移植后,对CCl4诱导的大鼠肝硬化模型的治疗作用.方法:SD♂大鼠45只随机分为对照组、门脉移植组及尾静脉移植组.所有大鼠经腹腔皮下注射CCl4混合物8wk.第6周时门静脉组及尾静脉组分别从肠系膜上静脉及尾静脉注射大鼠脂肪间质干细胞悬液每只2mL(细胞数量为2×106个),对照组自尾静脉注射等容量的细胞培养液.细胞移植前后取血检测肝功能指标.取肝脏标本并行包埋切片,HE染色后显微镜下观察各标本肝细胞变性坏死及肝硬化程度并进行病理评分.对所有实验数据行统计学分析.结果:门静脉及尾静脉移植组大鼠的肝功能指标(AST、ALT、ALB)较对照组有明显改善(142.2±31.2U/L,167.9±28.3U/Lvs354.2±26.4U/L;79.4±18.9U/L,85.8±21.4U/Lvs456.7±35.3U/L;26.3±2.0g/L,24.5±2.2g/Lvs17.2±1.7g/L,均P<0.05),但TBIL没有明显改善.与对照组相比,脂肪干细胞移植能抑制肝组织的变性坏死和纤维化形成.病理评分对比差异有统计学意义(P<0.05).结论:经门静脉及尾静脉移植脂肪间质干细胞对大鼠肝硬化模型有治疗作用,能改善肝功能及肝硬化程度.

AIM： To evaluate the therapeutic effect of adipose tissue-derived mesenchymal stem cells transplanted through caudal or portal vein for the hepatic cirrhosis model of rats induced by CCl4.METHODS： Forty-five healthy SD rats were randomly divided into control group, portal-vein group and caudal-vein group. All rats were subcutaneously injected carbon tetrachloride oily mixture continuously for 8 weeks. At the sixth week, portal-vein group and caudal-vein group were transplanted with rat adipose tissue-derived mesenchymal stem cells 2×106 each rat, respectively from superior mesenteric vein and caudal vein. The control group was injected isometric cell culture media. Liver function of rat was examined before and after cell transplantation. HE staining was performed on all liver specimen slices. The degeneration and necrosis of hepatic cells and the degree of liver fibrosis were observed under microscope, and further pathological evaluation was made according to observation results. All experiment data were analyzed by statistics. RESULTS： The liver function of portal-vein group and caudal-vein group was improved significantly in comparison with that of control group （AST： 142.2 ± 31.2 U/L, 167.9 ± 28.3 U/L vs 354.2 ± 26.4 U/L; ALT： 79.4 ± 18.9 U/L, 85.8 ± 21.4 U/L vs 456.7 ± 35.3 U/L; ALB： 26.3 ± 2.0 g/L, 24.5 ± 2.2 g/L vs 17.2 ± 1.7 g/L, all P 〈 0.05）, but the level of TBIL wasn’t improved. The transplantation of adipose tissue-derived mesenchymal stem cells inhibited the degeneration and necrosis of hepatic tissue and improved liver fibrosis of the rats. The difference of pathological evaluation between cell-transplanted group and control group was statistically significant （P 〈 0.05）. CONCLUSION： The transplantation of adipose tissue-derived mesenchymal stem cells through portal and caudal vein has therapeutic effect for the hepatic cirrhosis model of rats. It can improve liver function and inhibit liver fibrosis.