FXR在胆管癌大鼠胆管组织中的表达状况

Farnesyl X receptor expression in rat bile duct cancer

目的:本研究通过建立胆管癌大鼠模型,以法尼基衍生物X受体(farnesyl X receptor,FXR)为研究对象,初步探讨FXR在胆管癌大鼠胆管肿瘤组织中的表达状况,以期为治疗胆管癌找到新的方法.方法:取Wistar大鼠(■、体质量160g±8g)70只,随机分为2组,每组35只:普通饮食对照组(简称对照组)予以普通饮食、3'-甲基-4-二甲基氨偶氮苯(3'-Me-DAB)饮食实验组(简称实验组)予以含3'-Me-DAB饮食.经过20wk,建立胆管癌大鼠模型,取对照组胆管组织和实验组胆管肿瘤组织:(1)实时荧光定量PCR(real-time quantitative PCR,qRT-PCR)检测胆管组织和胆管肿瘤组织的FXR基因表达的强度;(2)石蜡切片后用免疫组织化学SP法检测胆管组织和胆管肿瘤组织的FXR蛋白表达的强度.结果:(1)qRT-PCR结果显示:FXR/GAPDH比率在对照组胆管组织中为32,在实验组胆管肿瘤组织中为9,两组间的表达有统计学差异;(2)免疫组织化学SP法结果显示,对照组胆管组织FXR表达阳性率为72.6%,实验组胆管肿瘤组织FXR表达阳性率为21.3%,存在统计学意义(P<0.05).结论:实验组大鼠胆管肿瘤组织的FXR基因的表达较对照组胆管组织减少,提示我们在胆管癌的治疗中,FXR基因有成为新治疗靶点的可能.

AIM：To develop a rat model of bile duct cancer and detect farnesyl X receptor（FXR） expression in bile duct cancer tissues of this model,in order to provide a new method for the prevention and treatment of bile duct cancer.METHODS：Seventy Wistar rats were randomly divided into either a control group or an experimental group,with 35 rats in each group.The control group was fed an ordinary diet,and the experimental group was fed a3＇-Me-DAB diet.After 20 wk,the bile duct cancer model was successfully established.Bile duct tissues were taken from rats of the control group and bile duct cancer tissues were taken from rats of the experimental group to detect the mRNA expression of FXR by realtime quantitative PCR（qRT-PCR） and protein expression by immunohistochemistry.RESULTS：qRT-PCR analysis showed that the relative expression level of FXR in the bile duct tissues was significantly higher that in the bile duct cancer tissues.Immunohistochemistry showed that in the experimental group,the positive expression rate of FXR was 21.3%,significantly lower than 72.6%in the control group（χ^2=10.17,P〈0.05）.CONCLUSION：The expression of FXR decreases significantly in rat bile duct cancer,which suggests that drugs targeting FXR may be a new therapeutic strategy for bile duct cancer.