[摘 要] 目的：探讨月见草素B调控磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）/核因子-κB（NF-κB）通路对卵巢癌SKOV3细胞恶性生物学行为的影响。方法：CCK-8法测定月见草素B对SKOV3细胞的半数抑制浓度（IC50），参考IC₅₀值及相关文献确定后续实验剂量。SKOV3细胞分为对照组，月见草素B低（6.25 μmol/L）、中（12.5 μmol/L）、高（25 μmol/L）剂量组，PI3K抑制剂（LY294002）组，月见草素B高剂量 + PI3K激活剂（740Y-P）组。CCK-8法、5-乙炔基-2'-脱氧尿苷（EdU）染色法检测各组细胞增殖能力；Transwell侵袭实验、划痕实验、流式细胞术分别检测各组细胞侵袭、迁移能力与凋亡情况；RT-qPCR检测各组细胞中增殖相关基因细胞周期蛋白D1（Cyclin D1）、迁移相关基因迁移侵袭增强子1（MIEN1）及凋亡相关基因p53 mRNA表达情况；Western blotting检测各组细胞中PI3K/AKT/NF-κB通路相关蛋白p-PI3K、p-AKT、NF-κB p65的表达。结果：月见草素B处理SKOV3细胞24 h的IC₅₀值为28.70 μmol/L。与对照组相比，月见草素B低、中、高剂量组及LY294002组SKOV3细胞增殖能力、侵袭细胞数及划痕愈合率均降低（均P < 0.05），Cyclin D1、MIEN1 mRNA及p-PI3K、p-AKT、NF-κB p65蛋白表达下调（均P < 0.05），而细胞凋亡率与p53 mRNA表达则升高（均P < 0.05）；与LY294002组相比，高剂量月见草素B对SKOV3细胞增殖能力、侵袭细胞数及划痕愈合率的抑制作用更显著（均P < 0.05），对Cyclin D1、MIEN1 mRNA及p-PI3K、p-AKT、NF-κB p65蛋白的下调及对细胞凋亡率与p53 mRNA表达的上调均更明显（均P < 0.05）。与月见草素B高剂量组相比，月见草素B高剂量+740Y-P组SKOV3细胞增殖能力、侵袭细胞数及划痕愈合率升高（均P < 0.05），Cyclin D1、MIEN1 mRNA及p-PI3K、p-AKT、NF-κB p65蛋白表达上调（均P < 0.05），细胞凋亡率与p53 mRNA表达降低（P < 0.05）。结论：月见草素B可能通过抑制PI3K/AKT/NF-κB通路，抑制卵巢癌SKOV3细胞增殖、侵袭与迁移，并诱导细胞凋亡。

ObjectiveTo investigate the value of serum protoporphyrin IX (PPIX) measurement in evaluating liver damage in patients with HBV-related chronic liver diseases. MethodsA total of 110 patients who were diagnosed with HBV-related chronic liver diseases in The First Affiliated Hospital of Xi’an Medical University from October 2018 to October 2019 were enrolled as case group ［chronic hepatitis B (CHB) group with 50 patients, liver cirrhosis (LC) group with 40 patients, and hepatocellular carcinoma (HCC) group with 20 patients］, and 40 healthy individuals were enrolled as control group. High-performance liquid chromatography was used to measure serum PPIX. A one-way analysis of variance was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test or the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups; the receiver operating characteristic (ROC) curve was plotted to analyze diagnostic value; a Spearman correlation analysis was also performed to investigate correlation. ResultsThe CHB, HC, and HCC groups had a significantly higher level of PPIX than the control group ［44.29 (25.99-85.36) ng/dl, 72.73 (48.28-90.43) ng/dl, and 91.79 (68.34-121.52) ng/dl vs 15.43 (10.87-20.16) ng/dl, all P＜0.05］, and the patients with decompensated LC had a significant increase in the level of PPIX compared with those with compensated LC ［54.50(29.14~85.65) vs 76.09(53.47~104.37)，Z=-2.176, P＜0.05］. PPIX had a sensitivity of ＞85% and a specificity of ＞60% in the diagnosis of CHB, LC, and HCC. The patients in the latent stage of CHB had a significantly higher level of PPIX than those in the control group (Z=-4.303, P＜0.05). In the patients with LC, PPIX was moderately positively correlated with total bilirubin (TBil) (rs=0.587, P＜0.05) and moderately negatively correlated with albumin (rs=-0.408, P＜0.05); in the patients with HCC, PPIX was moderately positively correlated with TBil (rs=0.470, P＜0.05) and moderately negatively correlated with cholinesterase (rs=-0.459, P＜0.05). ConclusionElevated serum PPIX is an early event of liver damage in patients with HBV-related chronic liver diseases and can thus be used as a sensitive parameter for the early warning and assessment of liver damage.