Kikuchi N, Yamaguchi Y, Mori K, Takata N, Goto M, Makino Y, Hamaguchi H, Hisama N, Ogawa M
Department of Surgery II, Kumamoto University Medical School, Japan.
Hepatogastroenterology. 1994 Apr;41(2):170-3.
These experiments were undertaken to study the effects of cyclosporine on liver regeneration after an isogeneic orthotopic reduced-size hepatic transplantation in rats. The incorporation of bromodeoxyuridine into the DNA of the remnant hepatocytes was evaluated at various time points by immunohistochemical staining. Cyclosporine (10 mg/kg/day) significantly augmented BrdU incorporation into hepatocytes after hepatectomy. The maximum labeling index was observed at 24 hr after hepatectomy. In contrast, the maximum labeling index in the recipient rats not receiving cyclosporine was seen at 36 hr after reduced-size hepatic transplantation, and 10 mg/kg/day of cyclosporine decreased the labeling index at 36 hr after grafting. A lower dose of cyclosporine (3 mg/kg/day), however, significantly increased the labeling index in the recipient rats, which reached a peak at 24 hr after grafting as compared with the transplant recipients not receiving cyclosporine. This dosage shortened the time it took for the reduced-size hepatic transplant labeling index to peak. These findings suggest that after reduced-size hepatic transplantation, the liver graft is more sensitive to both hepatotrophic and hepatotoxic effects of cyclosporine.
进行这些实验是为了研究环孢素对大鼠同基因原位减体积肝移植后肝脏再生的影响。通过免疫组织化学染色在不同时间点评估溴脱氧尿苷掺入残余肝细胞DNA的情况。环孢素（10毫克/千克/天）显著增加了肝切除术后肝细胞中BrdU的掺入。在肝切除术后24小时观察到最大标记指数。相比之下，未接受环孢素的受体大鼠在减体积肝移植后36小时出现最大标记指数，且10毫克/千克/天的环孢素降低了移植后36小时的标记指数。然而，较低剂量的环孢素（3毫克/千克/天）显著增加了受体大鼠的标记指数，与未接受环孢素的移植受体相比，该指数在移植后24小时达到峰值。此剂量缩短了减体积肝移植标记指数达到峰值所需的时间。这些发现表明，减体积肝移植后，肝移植物对环孢素的促肝细胞生长和肝毒性作用更敏感。
