摘要
该研究观察BMSCs早期尾静脉移植对四氯化碳(carbon tetrachloride,CCl4)肝损伤模型大鼠的影响以及一贯煎的干预作用。雌性Wistar大鼠65只,随机分为正常组,模型组,细胞移植组,一贯煎组和一贯煎加细胞移植组。造模各组大鼠按3 mL·kg^-1每周2次腹腔注射50%CCl4橄榄油溶液,共9次;细胞移植组和一贯煎加细胞移植组在首次注射CCl4后立即经尾静脉注入第3代BMSCs 1×10^6个;用药组灌胃一贯煎水煎液。结果可见细胞移植和一贯煎均可降低首次造模48 h的血清ALT和AST。造模4周后,模型组血清ALT,AST,γ-GT活性增高,TBIL含量增高;肝组织SOD活性降低,MDA和TG含量增加;肝组织病理可见大泡型脂肪变性,油红O染色可见大量脂滴,天狼猩红染色未见明显胶原增生,血清TNF-α和IL-6含量升高(P<0.05)。BMSC细胞移植组大鼠肝功能和组织病理较模型组进一步恶化,肝组织可见少量胶原增生,肝组织SOD活性更低,MDA和TG含量进一步增高(P<0.05),血清TNF-α和IL-6含量较模型组升高(P<0.05);经一贯煎干预后,各检测指标均较模型组和细胞移植组有所改善。SRY原位杂交检测显示,BMSC移植后在心、肝、脾、肺、肾均可检测到SRY阳性表达,但以肝脏最多,经一贯煎干预后,SRY阳性细胞在肝脏表达减少。Western blot结果显示正常组高表达Wnt和β-catenin,CCl4造模后表达明显减少,细胞移植后有进一步降低的趋势,一贯煎组干预后则表达增高。该研究表明早期尾静脉BMSCs移植可加重大鼠CCl4肝损伤,促进肝纤维化形成,一贯煎可改善BMSCs移植加重的CCl4肝损伤,其机制与减少BMSCs归巢肝脏,上调Wnt/β-catenin信号通路有关。
The aim of this paper was to observe the function of bone marrow mesenchymal stem cell(BMSC) transplantation in process of liver injury induced by carbon tetrachloride(CCl4) in vivo and the intervention effect of Yiguanjian(YGJ), a compound of Chinese herbal medicine. Wistar rats were randomly divided into five groups: normal group, model group, cell transplantation(CT) group, YGJ group and cell transplantation plus Yiguanjian(CTY) group. Liver injury was induced through subcutaneous injection with CCl4 at a dose of 3 mL·kg^-1 body weight for 4 weeks, twice a week. They were injected for a total of 9 times. After the first injection with CCl4, rats in the CT group and CTY group were injected with the third-generation BMSCs at dose 1×10^6(suspended in 1 mL saline solution) via tail vein. Rats in the YGJ and CTY groups were also intragastrically administered with Yiguanjian once a day. Rat serum ALT and AST activities were increased significantly on the second day after injection with CCl4, while BMSC transplantation and Yiguanjian decreased their activities. After 4 weeks of injection with CCl4, serum ALT, AST and γ-GT activities, and serum TNF-α and IL-6 expressions were increased, while TBIL were decreased in model rats compared with normal rats. Meanwhile, liver cells edema, plasmatic loose, and numerous lipid droplets were observed in rats of the model group. BMSC transplantation aggravated liver injury compared with model rats, which was manifested by decreasing SOD activity, increased MDA, TG, TNF-α and IL-6 levels, and aggravated necrosis level of hepatocytes, fusion of lipid droplets, and collagen deposition in liver tissue. Yiguanjian decreased liver injury induced by CCl4 alone and CCl4 plus BMSC transplantation. SRY gene in situ hybridization method was used to detect the positive SRY expressions in heart, liver, spleen, lung and kidney, especially in liver, while Yiguangjian decreased liver SRY expression. Wnt and β-catenin showed high expressions in rats of normal group, which were decreased sig
作者
平键
陈红云
周扬
成扬
陈高峰
徐列明
PING Jian;CHEN Hong-yun;ZHOU Yang;CHENG Yang;CHEN Gao-fen;XU Lie-ming(Key Laboratory of Traditional Chinese Clinical Medicine,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Key Laboratory of Liver and Kidney Diseases of Ministry of Education of China,Shanghai University of Traditional Chinese Medicine ,Shanghai 201203,China;Department of Traditional Chinese Medicine,Changhai Hospital Affiliate to Naval Medical University,Shanghai 200433,China;Institute of Liver Disease,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2018年第19期3905-3912,共8页
China Journal of Chinese Materia Medica
基金
上海市科学技术委员会项目(15401902600)
关键词
骨髓间充质干细胞
一贯煎
肝损伤
四氯化碳
细胞移植
bone marrow mesenchymal stem cells
Yiguanjian
liver injury
carbon tetrachloride
cell transplantation