索拉菲尼和伊马替尼对肺动脉平滑肌细胞增殖和糖代谢作用的比较研究

Effect of sorafenib and imatinib on the proliferation and metabolism of pulmonary artery smooth muscle cells

目的比较索拉菲尼和伊马替尼对血小板衍生生长因子(PDGF)诱导肺动脉平滑肌细胞(PASMCs)增殖及糖代谢途径转变的作用。方法分离培养SD大鼠PASMCs,给予PDGF刺激建立细胞增殖模型,分别使用不同浓度的索拉菲尼和伊马替尼处理细胞;MTT检测细胞增殖率;Western blot检测增殖细胞核抗原(PCNA)和细胞代谢关键蛋白表达;试剂盒检测葡萄糖摄取和乳酸生成。结果与正常对照组相比,PDGF明显促进PASMCs的增殖,并诱导细胞的代谢向糖酵解转变,表现在葡萄糖的摄取和乳酸生成明显增加,Glut1、Glut4、MCT4、LDH的表达水平显著增加,PDH表达水平明显减少;与PDGF处理组相比,索拉菲尼和伊马替尼均能显著抑制PDGF诱导的PASMCs的增殖,并有效逆转PDGF诱导的PASMCs有氧糖酵解;与索拉菲尼处理组相比,伊马替尼明显降低MCT4(2μmol·L^-1)和LDH(2、4μmol·L^-1)的表达,但PASMCs增殖和Glut1、Glut4、PDH表达差异无统计学意义。结论索拉菲尼和伊马替尼均可抑制PDGF诱导的PASMCs增殖和逆转有氧糖酵解,两者作用无明显差别。

Objective To compare the effect of sorafenib and imatinib on the proliferation and metabolic transformation of pulmonary artery smooth muscle cells(PASMCs)induced by platelet derived growth factor(PDGF).Methods PASMCs were isolated from SD rats,stimulated by PDGF,and treated with different concentrations of sorafenib and imatinib.The cell proliferation was detected by MTT.Western blot was performed to detect the expression of PCNA.And the key proteins of cell metabolism.Levels of extracellular glucose consumption and lactate production were determined by assay kit.Results PDGF significantly promoted the proliferation of PASMCs and induced the cell metabolism transform to glycolysis as compared with those in the normal control group,which was reflected in increased glucose uptake and lactate production,as well as increased expression of Glut1,Glut4,MCT4 and LDH,and decreased PDH expression.Compared with the PDGF treatment group,sorafenib and imatinib significantly inhibited the PASMC proliferation and reversed the metabolic transformation of PASMCs induced by PDGF.Compared with the sorafenib treatment group,imatinib significantly reduced MCT4(2μmol·L^-1)and LDH(2,4μmol·L^-1)expression,but there was no significant difference in inhibiting PASMCs proliferation,Glut1,Glut4 and PDH expression induced by PDGF.Conclusion Both sorafenib and imatinib can inhibit PASMC proliferation and reverse the metabolic transformation of PASMCs induced by PDGF.No significant difference is found between the two drugs in inhibiting the proliferation and metabolic transformation of PASMCs induced by PDGF.