Ping Jian, Chen Hong-Yun, Zhou Yang, Cheng Yang, Chen Gao-Feng, 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.
Zhongguo Zhong Yao Za Zhi. 2018 Oct;43(19):3905-3912. doi: 10.19540/j.cnki.cjcmm.20180522.007.
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) 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 1×10⁶ (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 -GT activities, and serum TNF- 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- 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 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 -catenin showed high expressions in rats of normal group, which were decreased significantly in rats of models group, while Yiguanjian increased their expressions. In conclusion, BMSC transplantation could exacerbate liver injury, while Yiguanjian could protect liver injury induced by CCl₄ and BMSC transplantation, which was related to decreasing the homing of BMSCs to liver and up-regulating Wnt/-catenin signaling pathway.
本文旨在观察骨髓间充质干细胞（BMSC）移植在四氯化碳（CCl₄）诱导的肝损伤过程中的作用以及中药复方一贯煎（YGJ）的干预效果。将Wistar大鼠随机分为五组：正常组、模型组、细胞移植（CT）组、一贯煎组和细胞移植加一贯煎（CTY）组。通过皮下注射剂量为3 mL·kg⁻¹体重的CCl₄诱导肝损伤，每周2次，共4周，总共注射9次。首次注射CCl₄后，CT组和CTY组大鼠经尾静脉注射剂量为1×10⁶的第三代BMSCs（悬浮于1 mL盐溶液中）。YGJ组和CTY组大鼠还每天灌胃给予一贯煎。注射CCl₄后第2天，大鼠血清ALT和AST活性显著升高，而BMSC移植和一贯煎降低了它们的活性。注射CCl₄ 4周后，与正常大鼠相比，模型大鼠血清ALT、AST和-GT活性以及血清TNF-和IL-6表达升高，而TBIL降低。同时，模型组大鼠观察到肝细胞水肿、细胞质疏松和大量脂滴。与模型大鼠相比，BMSC移植加重了肝损伤，表现为SOD活性降低、MDA、TG、TNF-和IL-6水平升高，肝细胞坏死程度加重、脂滴融合以及肝组织胶原沉积增加。一贯煎减轻了单独CCl₄和CCl₄加BMSC移植诱导的肝损伤。采用SRY基因杂交方法检测心脏、肝脏、脾脏、肺和肾脏中SRY阳性表达，尤其是在肝脏中，而一贯煎降低了肝脏SRY表达。Wnt和-β-连环蛋白在正常组大鼠中高表达，在模型组大鼠中显著降低，而一贯煎增加了它们的表达。总之，BMSC移植可加重肝损伤，而一贯煎可保护CCl₄和BMSC移植诱导的肝损伤，这与减少BMSCs归巢至肝脏以及上调Wnt/β-连环蛋白信号通路有关。
