Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, 980-0872, Japan.
Division of Transplantation and Regenerative Medicine, Tohoku University Graduate School of Medicine, 980-0872, Sendai, Japan.
Sci Rep. 2022 Mar 10;12(1):4241. doi: 10.1038/s41598-022-08237-6.
Clinical hepatocyte transplantation (HTx) is only performed without general anesthesia, while inhalation anesthetics are usually used in animal experiments. We hypothesized that isoflurane may be a possible reason for the discrepancy between the results of animal experiments and the clinical outcomes of HTx. Syngeneic rat hepatocytes (1.0 × 10) were transplanted to analbuminemic rats with (ISO group) and without (AW group) isoflurane. The serum albumin, AST, ALT, LDH levels and several inflammatory mediators were analyzed. Immunohistochemical staining and ex vivo imaging were also performed. The serum albumin levels of the ISO group were significantly higher in comparison to the AW group (p < 0.05). The serum AST, ALT, LDH levels of the ISO group were significantly suppressed in comparison to the AW group (p < 0.0001, respectively). The serum IL-1β, IL-10, IL-18, MCP-1, RNTES, Fractalkine and LIX levels were significantly suppressed in the ISO group. The ischemic regions of the recipient livers in the ISO group tended to be smaller than the AW group; however, the distribution of transplanted hepatocytes in the liver parenchyma was comparable between the two groups. Isoflurane may at least in part be a reason for the discrepancy between the results of animal experiments and the clinical outcomes of HTx.
临床肝细胞移植(HTx)仅在无全身麻醉下进行,而吸入麻醉剂通常用于动物实验。我们假设异氟醚可能是动物实验结果与 HTx 临床结果之间差异的一个可能原因。将 1.0×10 的同基因大鼠肝细胞移植到白蛋白缺乏症大鼠中(ISO 组)和没有异氟醚(AW 组)。分析血清白蛋白、AST、ALT、LDH 水平和几种炎症介质。还进行了免疫组织化学染色和离体成像。与 AW 组相比,ISO 组的血清白蛋白水平明显升高(p<0.05)。与 AW 组相比,ISO 组的血清 AST、ALT、LDH 水平明显受到抑制(分别为 p<0.0001)。ISO 组的血清 IL-1β、IL-10、IL-18、MCP-1、RNTES、Fractalkine 和 LIX 水平明显受到抑制。ISO 组受体肝脏的缺血区域比 AW 组小;然而,两组肝实质中移植肝细胞的分布相似。异氟醚至少部分可能是动物实验结果与 HTx 临床结果之间差异的原因。