连接蛋白/缝隙连接细胞间通讯对大鼠肝卵圆细胞增殖调控作用

背景：缝隙连接蛋白介导的缝隙连接细胞间通讯（gap junction intercellular communication,GJIC）是细胞间最重要的信息交流形式。目的：验证CX/GJIC对卵圆细胞的增殖调控作用。方法：Wistar大鼠分为4组。对照组正常饮食;2-AAF/PH组按改良Solt-Farber法建立卵圆细胞增殖动物模型;苯巴比妥组予以苯巴比妥饮水7d,第8天按2-AAF/PH组建模,苯巴比妥饮水持续至实验结束;三七总皂苷组按2-AAF/PH组建模时予以三七总皂苷25mg/（kg？d）腹腔内注射,并持续实验结束。结果与结论：造模后肝脏连接蛋白呈时空特异性表达,先下调后逐渐恢复,连接蛋白43表达于卵圆细胞,先升高后逐渐恢复;采用苯巴比妥改变大鼠2-AAF/PH模型肝脏的连接蛋白32、连接蛋白43时空表达模式后,可下调肝脏的GJIC,减少卵圆细胞与偶联细胞间GJIC,解除卵圆细胞生长抑制,促进卵圆细胞的增殖;三七总皂苷可以增加大鼠2-AAF/PH模型肝脏的连接蛋白32表达、滞后连接蛋白43的表达,增加卵圆细胞与偶联细胞间GJIC,使卵圆细胞增殖峰低、滞后、持续时间长;通过下调大鼠2-AAF/PH模型肝脏的GJIC,可使卵圆细胞增殖早、增殖水平高;上调GJIC使卵圆细胞增殖峰低、滞后、持续时间长,CX/GJIC可以调节体内卵圆细胞的增殖、分化过程。

Regulatory effect of connexin/gap junction intercellular communication on proliferation of rat hepatic oval cells

BACKGROUND：Gap junction intercellular communication（GJIC） mediated by connexin（CX） is the pivotal pattern of communication in multicellular organism.OBJECTIVE：To observe the regulatory effect of CX/GJIC on hepatic oval cell proliferation.METHODS：Wistar rats were assigned to four groups.Control group received normal diet.Animal models of hepatic oval cell proliferation were established in the 2-acetylaminofluorene/partial hepatectomy（2-AAF/PH） group according to modified Solt-Farber method.Phenobarbital group received phenobarbital drinking for 7 days,and on day 8,models were established as the 2-AAF/PH group.Phenobarbital drinking lasted till the end of the test.Panax notoginseng saponins（PNS） group received PNS 25 mg/kg daily by intraperitoneal injection during model establishment as the 2-AAF/PH group,lasting till the end of the test.RESULTS AND CONCLUSION：The patterns of CX expression were different in spatial and temporal in the rat liver after 2-AAF/PH,decreased and then recovered.The CX43 protein was expressed in hepatic oval cells,and they were increased at first and then to recover.GJIC was inhibited by altered the spatial and temporal expression patterns of CX in the rats liver after 2-AAF/PH（with phenobarbital） that can accelerate the proliferation of hepatic oval cells.GJIC was increased by enhancing the expression level of CX in the rats liver after2-AAF/PH（with PNS） that can accurately activate hepatic oval cells proliferation.The peak of hepatic oval cells proliferation was decreased,delayed and lasted long time.To decrease the GJIC in the rat liver of 2-AAF/PH that can accelerate and enhance the proliferation of hepatic oval cells,whereas to increase the GJIC can decrease,delay and last long time the proliferation of hepatic oval cells.These suggest that the proliferation and differentiation of hepatic oval cells were modulated by CX/GJIC.