Department of General Surgery (Hepatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan Province, China.
Sci Rep. 2022 May 24;12(1):8741. doi: 10.1038/s41598-022-12850-w.
The study objective was to detect the expression of farnesoid X receptor (FXR) in a rat model of hilar cholangiocarcinoma to provide a new therapeutic target for gene therapy in hilar cholangiocarcinoma. Sixty male Wistar rats (weighing 190 ± 8 g) were randomly divided into three groups (experimental group, control group and sham operation group, 20 rats in each group). The three groups were fed a standard diet. The QBC939 cell suspension of cholangiocarcinoma was injected into the hilar bile duct in the experimental group with a microsyringe. The control group was injected with normal saline, and the sham operation group was not injected with any drugs. A modified tail suspension test (TST) was used to evaluate the mental state and physical activity of rats every day. At 5 weeks, one rat in the experimental group was euthanized, and the changes in the hilar bile duct were recorded. The procedure was repeated at one and half months. After one and half months, hilar cholangiocarcinoma only occurred in the experimental group. Pathological examination confirmed the formation of tumours, and hilar bile duct tissues were taken from the three groups. FXR expression in the hilar bile duct was detected by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. After two weeks, the rats in the experimental group ate less, and their weight was significantly reduced. One and half months later, hilar cholangiocarcinoma was detected in 16 rats in the experimental group. The levels of alanine aminotransferase and aspartate transaminase in the experimental group were higher than those in the other two groups. The ratio of FXR/GAPDH mRNA was significantly different among the hilar cholangiocarcinoma, control and sham operation groups. Under the light microscope, FXR protein reacted with anti-FXR antibody and showed granular expression. Every pathological section included 4800 cells. A total of 1856 positive cells were in the experimental group, 3279 positive cells were in the control group, and 3371 positive cells were in the sham operation group. FXR expression in the hilar cholangiocarcinoma of rats was significantly lower than that in normal hilar bile duct tissues, suggesting that drugs targeting FXR may be a new strategy for the treatment of hilar cholangiocarcinoma.
本研究旨在检测法尼醇 X 受体（FXR）在大鼠肝门部胆管癌模型中的表达，为肝门部胆管癌的基因治疗提供新的治疗靶点。将 60 只雄性 Wistar 大鼠（体重 190±8g）随机分为三组（实验组、对照组和假手术组，每组 20 只）。三组均给予标准饮食。实验组用微量注射器向肝门胆管内注射胆管癌细胞悬液，对照组注射生理盐水，假手术组不注射任何药物。每天采用改良的悬尾试验（TST）评估大鼠的精神状态和体力活动。第 5 周处死实验组中的 1 只大鼠，记录肝门胆管的变化，1 个半月后重复上述操作。1 个半月后，仅实验组大鼠发生肝门部胆管癌。病理检查证实肿瘤形成，取三组大鼠肝门胆管组织。采用实时聚合酶链反应（RT-PCR）和免疫组织化学法检测肝门胆管中 FXR 的表达。两周后，实验组大鼠进食减少，体重明显减轻。1 个半月后，实验组 16 只大鼠检出肝门部胆管癌。实验组大鼠丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平高于其他两组。FXR/GAPDH mRNA 比值在肝门部胆管癌组、对照组和假手术组之间差异有统计学意义。光镜下，FXR 蛋白与抗 FXR 抗体反应，呈颗粒状表达。每例病理切片包括 4800 个细胞，实验组共 1856 个阳性细胞，对照组共 3279 个阳性细胞，假手术组共 3371 个阳性细胞。大鼠肝门部胆管癌组织中 FXR 表达明显低于正常肝门胆管组织，提示针对 FXR 的药物可能成为治疗肝门部胆管癌的新策略。
