摘要
背景:间充质干细胞对肝衰竭大鼠的肝脏具有保护及修复作用,但具体机制尚未完全明确。目的:观察人脂肪间充质干细胞尾静脉注射对急性肝衰竭大鼠肝脏损伤的保护作用,并探讨其可能的机制。方法:将36只SD大鼠(购自青岛市大任富成畜牧有限公司)随机等分为对照组、模型组和移植组。模型组和移植组大鼠通过腹腔注射D-氨基半乳糖建立急性肝衰竭模型。造模1 d后,移植组注射人脂肪间充质干细胞悬液,模型组注射等量生理盐水。细胞移植1 d和3 d,检测血清中丙氨酸氨基转移酶、天冬氨酸氨基转移酶、总胆红素水平。细胞移植3 d,检测血清中肿瘤坏死因子α、白细胞介素6、白细胞介素10水平;苏木精-伊红染色观察肝脏病理形态学变化;Western blot检测肝组织中糖原合成酶激酶3β蛋白的表达。结果与结论:(1)与模型组相比,移植组血清中丙氨酸氨基转移酶、天冬氨酸氨基转移酶、总胆红素、肿瘤坏死因子α、白细胞介素6和白细胞介素10水平降低(P<0.05);(2)移植组肝脏组织炎症反应和变性坏死程度较模型组减轻;(3)移植组肝组织中糖原合成酶激酶3β活性较模型组减弱(P <0.05);(4)结果表明,人脂肪间充质干细胞可以减轻急性肝衰竭大鼠肝脏炎症反应和病理损伤,改善肝脏功能,其机制可能与抑制糖原合成酶激酶3β活性有关。
BACKGROUND:Mesenchymal stem cells can protect and repair the liver of rats with liver failure,but the mechanisms are not completely clear.OBJECTIVE:To explore the protective effects and related mechanisms of intravenous injection of human adipose-derived mesenchymal stem cells on acute liver failure in rats.METHODS:Thirty-six Sprague-Dawley rats(provided by Qingdao Daren Fucheng Animal Husbandry Co.,Ltd.in China)were randomly divided into control group,model group and transplantation group.Animal models of acute liver failure were established by intraperitoneal injection of D-galactosamine in the model group and the transplantation group.One day after modeling,the rats in the transplantation group were injected with human adipose-derived mesenchymal stem cell suspension,and those in the model group were injected with the same amount of saline.After 1 and 3 days of cell transplantation,the serum levels of alanine aminotransferase,aspartate aminotransferase,and total bilirubin were measured.Three days after cell transplantation,the serum levels of tumor necrosis factor-α,interleukin-6 and interleukin-10 were detected,the pathological changes of the rat liver were observed by hematoxylin-eosin staining,and the activity of glycogen synthase kinase-3βprotein in the liver tissue was detected by western blot.RESULTS AND CONCLUSION:Compared with the model group,there was a significant reduction in the serum levels of alanine aminotransferase,aspartate aminotransferase,total bilirubin,tumor necrosis factor-α,interleukin-6 and interleukin-10 in the transplantation group(P<0.05).Inflammation and necrosis of liver tissues in the transplant group were alleviated compared with the model group.The activity of glycogen synthase kinase 3βin the liver tissue of the transplanted group was lower than that of the model group(P<0.05).Overall,these results indicate that human adipose-derived mesenchymal stem cells can alleviate hepatic inflammation and pathological injury,and improve the liver function in rats with acute hepatic failure.Moreover,the mechanism may be related to the inhibition of glycogen synthase kinase 3βactivity.
作者
张德国
谭雪莹
唐楠
黄飞
史光军
Zhang Deguo;Tan Xueying;Tang Nan;Huang Fei;Shi Guangjun(Department of Hepatobiliary Surgery,Affiliated Qingdao Municipal Hospital of Qingdao University,Qingdao 266000,Shandong Province,China)
出处
《中国组织工程研究》
CAS
北大核心
2019年第9期1416-1421,共6页
Chinese Journal of Tissue Engineering Research
基金
国家自然科学基金(81601617)
项目负责人:谭雪莹
山东省医药卫生科技发展项目(2015WS0324)
项目负责人:谭雪莹~~
