CAJ | 학술논문

目的研究生长抑素对瘦素诱导大鼠肝星状细胞(HSC)的活化增殖、蛋白酪氨酸磷酸酶1B(PTP1B)表达及JAK2-STAT3通路的影响，探讨生长抑素抗肝纤维化的相关机制。方法以重组大鼠瘦素作用于HSC-T6细胞(100 ng/ml)，同时加入各浓度的生长抑素(10-6、10-7、10-8、10-9、10-10 mol/L)。在处理24 h后，采用CCK-8法检测HSC增殖的变化，免疫细胞化学检测 p-JAK2及 p-STAT3蛋白表达， RT-PCR法检测α-平滑肌肌动蛋白(α-SMA)和 PTP1B 的mRNA表达。结果 CCK-8法显示生长抑素可通过剂量依赖方式抑制瘦素诱导的HSC-T6细胞增殖( P<0.05)；免疫细胞化学检测显示，生长抑素组HSC-T6细胞质p-JAK2及细胞核内 p-STAT3蛋白表达明显低于瘦素对照组( P <0.05)；RT-PCR法检测生长抑素干预组 HSC α-SMA mRNA的表达较瘦素对照组及空白对照组明显降低(P<0.05)，而PTP1B的mRNA表达量升高(P<0.05)。结论生长抑素能上调PTP1B的表达，阻断瘦素在HSC内 JAK2-STAT3信号通路的转导，并且抑制瘦素诱导HSC的活化与增殖。
목적연구생장억소대수소유도대서간성상세포(HSC)적활화증식、단백락안산린산매1B(PTP1B)표체급JAK2-STAT3통로적영향，탐토생장억소항간섬유화적상관궤제。방법이중조대서수소작용우HSC-T6세포(100 ng/ml)，동시가입각농도적생장억소(10-6、10-7、10-8、10-9、10-10 mol/L)。재처리24 h후，채용CCK-8법검측HSC증식적변화，면역세포화학검측 p-JAK2급 p-STAT3단백표체， RT-PCR법검측α-평활기기동단백(α-SMA)화 PTP1B 적mRNA표체。결과 CCK-8법현시생장억소가통과제량의뢰방식억제수소유도적HSC-T6세포증식( P<0.05)；면역세포화학검측현시，생장억소조HSC-T6세포질p-JAK2급세포핵내 p-STAT3단백표체명현저우수소대조조( P <0.05)；RT-PCR법검측생장억소간예조 HSC α-SMA mRNA적표체교수소대조조급공백대조조명현강저(P<0.05)，이PTP1B적mRNA표체량승고(P<0.05)。결론생장억소능상조PTP1B적표체，조단수소재HSC내 JAK2-STAT3신호통로적전도，병차억제수소유도HSC적활화여증식。
Objective To investigate the effect of somatostatin on leptin-induced activation, proliferation, PTP1B expression and JAK2-STAT3 signaling of rat hepatic stellate cells ( HSC-T6 ) . Methods HSC-T6 cells were trea-ted with recombinant rat leptin (100 ng/ml) and various concentrations of somatostatin (10 -6,10 -7,10 -8,10 -9, 10 -10 mol/L). After incubation for 24 h, the cell proliferation rates of the groups were determined by CCK-8. Im-munocytochemical staining assay was applied to evaluate phosphorylation of Janus kinase 2 ( JAK2 ) and protein ex-pression of signal transducers and activators of transcription 3 ( STAT3 ) . The mRNA expression of α-SMA and PTP1B was evaluated by RT-PCR. Results With CCK-8, somatostatin could promote leptin-induced proliferation of hepatic stellate cells in a dose-adependent manner ( P<0.05 ) . The expressions of cytoplasmic p-JAK2 and nu-cleic p-STAT3 after somatostatin intervention were significantly lower than that of the leptin control group ( P <0.05). Compared with the group with leptin,α-SMA mRNA of somatostatin group was significantly down-regulated after the treatment ( P<0.05 ) , while PTP1 B mRNA expression was significantly increased ( P<0.05 ) . Conclu-sion Somatostatin up-regulates PTP1B expression, inhibits JAK2-STAT3 signal transduction in HSC and the cell activation and proliferation induced by leptin.