Objective: Placental trophoblast cells (TCs) produce soluble Flt-1 (sFlt-1). Hypoxia induces placental oxidative stress and modulates trophoblast function. The aim of this study was to investigate whether hypoxia mediates TC sFlt-1 production and whether increased sFlt-1 production correlates with increased oxidative stress in placental TCs. Methods: Placentas were obtained immediately after delivery from normal pregnant women (n=8). Placental TCs were isolated by Dispase digestion of villous tissue and purified by Percoll gradient centrifugation. Isolated TCs were cultured under normoxia (21% O2: 5%CO2/95% air) and hypoxia (2% O2/5% CO2/93% N2) conditions for 3 days in vitro. TC productions of sFlt-1, VEGF, and PlGF were measured by enzyme-linked immunosorbent assay (ELISA). Lipid peroxide production and superoxide dismutase (CuZn-SOD) levels were evaluated. Messenger RNA expressions of Flt-1, VEGF and PlGF were determined by RT-PCR. Messenger RNA expressions for superoxide dismutase (CuZn-SOD) and heme oxygenase-1 (HO-1) were also determined. Data are expressed as meanGSE. A p level less than 0.05 was considered statistically different. Results: Our results show that sFlt-1 production was significantly increased by TCs cultured under hypoxia condition that correlates with increased lipid peroxide production. We also found that under hypoxia condition: (1) the ratio of PlGF/VEGF production was reversed; (2) the ratio of lipid peroxides to superoxide dismutase production was increased. The increased mRNA expressions for Flt-1 and VEGF and the decreased mRNA expression for PlGF in TCs were consistent with the protein productions under hypoxia condition. Conclusion: We concluded that upregulation of sFlt-1 and unbalanced PlGF/VEGF production associated with increased oxidative stress are consequences of hypoxia in placental TCs. Our results suggest that placental TCs are major sources of sFlt-1 and VEGF levels in the maternal circulation in women with preeclampsia. Placenta (2005), 26, 210e217

Objectives: Soluble endothelial-cell adhesion molecules (ICAM, VCAM and PECAM) are markers of endothelial activation, and are elevated in the maternal circulation during pregnancy and even further increased in pregnancies complicated by pre-eclampsia (PE). To identify possible sources of endothelial activators during pregnancy, we addressed whether factors released from placental trophoblast cells (TCs) activate endothelial cells (ECs) to enhance adhesion molecule expression on ECs. We also examined whether proteases released by placental cells induce the endothelial cell surface molecule expression in PE. Methods: Confluent ECs were co-cultured with placental TCs derived from normal (n=9) or PE (n=8) pregnancies or with placental conditioned media (CM) derived from PE placental cultures (n=7). ICAM, VCAM, P-selectin and E-selectin were quantified using an enzyme-linked immunosorbent assay (ELISA). The protease inhibitors 2-macroglobulin ( 2M), thrombin inhibitor (TI) and chymotrypsin inhibitor (CI) were tested in the co-culture system. mRNAs for ICAM, VCAM, P-selectin and E-selectin were determined by RNase protection assay (RPA). NF- B activity in ECs was also determined. Results: (1) ICAM and VCAM expression was significantly increased on ECs co-cultured with both normal-TCs and PE-TCs, compared to control ECs (P<0.01). ICAM and VCAM expression in ECs co-cultured with normal-TCs did not differ from ECs co-cultured with PE-TCs. (2) E-selectin expression was increased on ECs co-cultured with normal-TCs (P<0.05) and further increased in ECs co-cultured with PE-TCs (P<0.01). (3) P-selectin expression was increased on ECs co-cultured with PE-TCs, but not ECs co-cultured with normal-TCs compared to control ECs (P<0.05). (4) 2M and TI did not alter the ICAM, VCAM, P-selectin and E-selectin expression on ECs induced by PE-CM. (5) CI blocked the upregulation of P-selectin and E-selectin (P<0.05), but not ICAM and VCAM expression, in ECs cultured with PE-CM. (6) Changes in mRNA for ICAM, VCAM, P-selectin and E-selectin paralleled the increases in protein expression on ECs cultured with PE-CM. (7) NF- B activity was alsoincreased in cells challenged with PE-CM. Conclusions: (1) Factor(s) released from both normal-TCs and PE-TCs promote ICAM and VCAM expression on ECs. (2) Factor(s) released from PE-TCs significantly increase EC P-selectin and E-selectin expression. (3) CI blocks the upregulation of P-selectin and E-selectin on ECs induced by factors released from PE placental cells, suggesting that chymotrypsin is responsible for the increased endothelial expression of P-selectin and E-selectin in pre-eclampsia. Placenta (2003), 24, 851-861

目的研究异丙肾上腺素（ISP）致大鼠心肌损伤模型中，编码电压门控Na+通道α亚单位基因SCN5A表达的变化，以及硒对其表达的影响。方法24只Wistar大鼠雌雄各半，随机分为3组，即对照组、ISP组、硒+ISP组。测定心肌丙二醛（MDA）的水平；采用逆转录聚合酶链反应（RT-PCR）和Western-blot方法检测心肌SCN5A基凶的表达变化。结果与ISP组比较，硒+ISP组MDA显著降低（P<0.05），但高于对照组（P<0.05）；ISP组SCN5A基凶mRNA和蛋白的表达均较对照组显著增加，而硒+ISP组降低其表达。结论异丙肾上腺素可使心肌SCN5A基因mRNA和蛋白的表达显著增高：硒对异丙肾上腺素致大鼠心肌损伤有保护作用并能逆转ISP引起的SCN5A基凶表达的改变。

目的探讨阿霉素对肝细胞的损伤机制及亚硒酸钠对肝细胞的保护作用。方法通过复制大鼠阿霉素性心肌损伤的动物模型，以亚硒酸钠作为保护因素，应用原位末端标记法（TUNEL）和免疫组化技术检测大鼠肝细胞凋亡和肝细胞转化生长因子1表达，并观察了大鼠血清中脂质过氧化含量。结果阿霉素组大鼠肝组织可见细胞凋亡和肝细胞中转化生长因子1的异常表达;阿霉素组大鼠血清中脂质过氧化物明显升高;亚硒酸钠对阿霉素的损伤有明显的保护作用。结论阿霉素诱导肝细胞凋亡可能是其肝脏损伤机制之一，并且细胞凋亡与转化生长因子1的高表达和血清中脂质过氧化水平升高有密切关系。