Objective To explore the impact of pioglitazone by endoplasmic reticulum stress apoptotic pathway on calcification of rat vascular smooth muscle cells in vitro, and its signal transduction and molecular mechanisms. Methods Calciifcation of cultured rat vascular smooth muscle cells(VSMCs)was produced by withβ-glycerophosphate(β-GP) and sodium pyruvate. The vascular smooth muscle cells cells (VSMCs) were treat with (10, 50, 100μmol/L) pioglitazone. Von kossa staining and alizarin red staining, calcium content, alkaline phosphatase activity were analyzed to estimate the extent of calcification. The apoptoticrate was analyzed by flowcy tometry and TUNEL. The mRNA expression of peroxisome proliferator-activated receptor(PPAR-γ), glucose regulated protein 78 (GRP78)and cysteine-containing aspartate-specific proteases-12 (caspase-12) were detected by quantitative real-time RT-PCR. Results Compared with the normal VSMCs, the calcium content and, ALP activity of the cells of the calcified VSMCs were significantly higher (P<0.05), pioglitazone in a dose-dependent manner to promote calcified rat vascular the calcium content of the smooth muscle cells (VSMCs) ALP activity, the cell apoptotic rate and the mRNA expression of PPAR-γ, GRP78 and caspase-12. Conclusion Pioglitazone can promoteβ-glycerophosphate-induced calciifcation of vascular smooth muscle cells, pioglitazone promote calciifcation of vascular smooth muscle cells may be though by endoplasmic reticulum stress apoptotic pathway.%目的：探讨吡咯列酮通过内质网应激致凋亡途径对大鼠血管平滑肌细胞钙化影响。方法利用β-甘油磷酸钠联合丙酮酸钠制备钙化血管平滑肌细胞模型，予不同浓度（10、50、100μmol/L）吡咯咧酮干预。用Von Kossa染色及茜素红S染色观察细胞钙化程度，用甲基百里香酚蓝法测定各组细胞中钙含量，磷酸苯二钠法测定细胞中碱性磷酸酶（ALP）活性。采用流式细胞术及TUNEL法检测细胞凋亡率，实时荧光定量RT-PCR检测各组细胞PPAR-γ、GRP78和caspased-12表达。观察吡咯列酮通过内质网应激致凋亡对大鼠血管平滑肌细胞钙化影响及其可能的分子机制。结果钙化血管平滑肌细胞其钙含量、ALP活性较普通细胞增多（P＜0.01），而吡格列酮呈剂量依赖性地促进钙化大鼠血管平滑肌细胞的钙含量、ALP活性，以及PPAR-γ、GRP78、caspase-12mRNA表达（P＜0.05）。结论吡咯列酮通过内质网应激致凋亡途径作用可促进β-磷酸甘油诱导的血管平滑肌细胞钙化，其作用可能与PPAR-γ及GRP78、caspase-12表达上调有关。
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