NF-κB在卵圆细胞增殖和分化中的作用及黄芩苷的调节机制

Role of NF-κB in hepatic oval cell proliferation: Implications for mechanism underlying protective effects of baicalin against liver injury

目的:探讨核转录因子-κB(nuclear factor kappa B,NF-κB)在卵圆细胞增殖分化中的作用及黄芩苷的调节机制.方法:64只健康SD大鼠随机分为假手术组、模型组、黄芩苷低剂量组和黄芩苷高剂量组.模型组采用2-乙酰氨基芴+2/3肝切除术(2-acetylaminofluorene+two thirds partial hepatectomy,2-AAF+2/3PH)的方法建立卵圆细胞增殖模型,黄芩苷干预组建立模型的同时分别给予50 mg/kg和100 mg/kg黄芩苷.各组分别于手术后第1、7、14、21天取材.HE染色观察肝组织病理学表现;免疫荧光技术、免疫组织化学检测HOC的增殖分化情况;RTPCR法和Western blot检测NF-κB表达.结果:本实验成功建立了卵圆细胞增殖模型,卵圆细胞在肝切除术后第7-14天增加明显,第14天达到峰值,第21天下降.NF-κB的表达趋势与卵圆细胞增殖一致.黄芩苷干预组卵圆细胞和NF-κB的表达均减少,与模型组相比差异均有统计学意义(P<0.05).结论:卵圆细胞的增殖和分化与NF-κB的激活有关.黄芩苷可能通过抑制NF-κB信号通路而抑制卵圆细胞的增殖,并诱导卵圆细胞向成熟的肝细胞及胆管细胞分化,这可能是黄芩苷作用于肝脏的一种机制.

AIM： To explore the role of nuclear factor kappa B（NF-κB） in hepatic oval cell proliferation and the possible mechanism underlying the therapeutic effect of baicalin against liver injury. METHODS： 64 SD rats were randomly divided into 4 groups： a sham operation group, a model group, a low-dose baicalin group and a high-dose baicalin group. 2-acetylaminofluorene plus 2/3 partial hepatectomy（2-AAF＋2/3PH） was used to establish the hepatic oval cell（HOC） proliferation model. The two baicalin groups were given 50 and 100 mg/kg of baicalin daily by lavage when modeling, respectively. The rats were killed on 1, 7, 14 and 21 d after PH in each group, and serum and liver tissue samples were collected. Hepatic pathological changes were observed by hematoxylin and eosin（HE） staining. Immunofluorescence, immunohistochemical staining, reverse transcription-polymerase chain reaction（RTPCR） and Western blot were used to evaluate the proliferation and differentiation of HOCs and the expression of NF-κB. RESULTS： The HOC proliferation model was successfully established. HOC proliferation began to increase after PH, peaked on the 14 th day and decreased on the 21 st day. The expression pattern of NF-κB was consistent with the proliferation pattern of HOCs, and they were both reduced by baicalin intervention.CONCLUSION： HOC proliferation is related to the activation of NF-κB. Baicalin could inhibit HOC proliferation possibly through the NF-κB signaling pathway, and this may be a possible mechanism for the therapeutic effect of baicalin against liver injury.