褪黑素对PDGF诱导肝纤维化的影响及其可能机制

Effect of melatonin on liver fibrosis induced by platelet-derived growth factor and its possible mechanism

摘要:

目的： 探讨褪黑素（melatonin，Mel）对血小板衍生生长因子（platelet-derived growth factor，PDGF）诱导的肝星状细胞-T6（hepatic stellate cell-T6，HSC-T6）中JAK2/STAT3信号通路的影响。方法： 将HSC-T6细胞分为6组：对照组、模型组、实验组（Mel 1 nmol/L、Mel 1 μmol/L、Mel 0.1 mmol/L）、抑制剂组（AG490为JAK2/STAT3通路的抑制剂），实时荧光聚合酶链式反应检测HSC-T6中α-平滑肌肌动蛋白（α-smooth muscle actin，α-SMA）、Ⅰ型胶原（collagen typeⅠ，collagen-Ⅰ）mRNA表达，免疫组化检测HSC-T6细胞中JAK-2、P-JAK2、STAT3、P-STAT3蛋白表达。结果： 与对照组比较，PDGF能明显激活HSC-T6增殖，明显上调HSC-T6中α-SMA、collagen-ⅠmRNA及JAK-2、P-JAK2、STAT3、P-STAT3表达；与模型组比较，褪黑素及JAK2/STAT3通路抑制剂可抑制PDGF诱导的HSC-T6增殖，明显下调α-SMA、collagen-ⅠmRNA及JAK-2、P-JAK2、STAT3、P-STAT3表达。结论： 褪黑素可抑制PDGF诱导的HSC-T6活化与增殖，其机制可能与抑制JAK2/STAT3信号通路有关，这可能是褪黑素改善肝纤维化的机制之一。

Abstract:

Objective: To investigate the effect of melatonin (Mel) on the JAK2/STAT3 signaling pathway of hepatic stellate cell-T6 (HSC-T6) induced by platelet-derived growth factor (PDGF). Methods: HSC-T6 cells were divided into 6 groups: control group, model group, experimental groups (Mel 1 nmol/L, Mel 1 μmol/L, Mel 0.1 mmol/L) and inhibitor group (AG490 JAK2/STAT3 pathway inhibitor). Real-time fluorescent polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of α-smooth muscle actin (α-SMA) and collagen typeⅠ (collagen-Ⅰ) in HSC-T6, and the protein expression detection of JAK-2, P-JAK2 and STAT3, P-STAT3 proteins in HSC-T6 cells was made by immunohistochemistry. Results: Compared with the control group, PDGF significantly activated the proliferation of HSC-T6, and significantly up-regulated the expression of α-SMA, collagen-ⅠmRNA and JAK-2, P-JAK2, STAT3 and P-STAT3 in HSC-T6.Compared with model group, Mel and JAK2/STAT3 pathway inhibitor inhibited PDGF induced HSC-T6 proliferation, and significantly down-regulated the expressions of α-SMA, collagen-ⅠmRNA and JAK-2, P-JAK2, STAT3 and P-STAT3.Conclusion: Mel can inhibit the activation and proliferation of HSC-T6 induced by PDGF, and the mechanism may be related to the inhibition of JAK2/STAT3 signaling pathway, which may be one of the mechanisms of melatonin improving liver fibrosis.