Mesangial cell regulation under the over expression of oxygen radical scavengers

肾小球系膜细胞（glomerular mesangial cells, MCs）是一种间质源性细胞，通过产生细胞因子在诱导氧自由基损伤中起关键作用，是临床上糖皮质激素治疗肾小球肾炎的靶点。在培养条件下，MC在糖皮质激素或肉豆蔻酸酯（PMA）刺激下表现出氧自由基和趋化因子的产生等多种作用。根据修正的MC辨析；通过cAMP和趋化因子的产生来评估实验性肾炎、免疫复合物、MC的EC-SOD的产生，MC在细胞外空间氧自由基毒性的降低中起重要作用。MC的EC-SOD生成在早期就得到了识别，并在融合状态下持续稳定。MCs分化标志物、氧自由基产生、氧自由基清除剂、EC-SOD产生与MCs分化呈正相关，与氧自由基产生呈负相关。糖皮质激素刺激可诱导MC稳定状态，提高EC-SOD和cAMP的产生，抑制IL-6和IL-8的产生，并呈剂量依赖性。而PMA刺激可诱导系膜细胞活化，提高IL-6和IL-8的产生，抑制EC-SOD和cAMP的产生。在无刺激条件下，EC-SOD的产生与cAMP含量呈正相关，与IL-6、IL-8的产生负相关。MC中EC-SOD生成的增强与cAMP生成的促进有关，导致IL-6和IL-8的产生受到抑制，可能在肾小球肾炎中起病理生理作用，提示糖皮质激素的药理作用之一。

The kidney glomerular mesangial cells (MCs) are mesenchymally derived cell in a pivotal position to induce the oxygen radical injury through the cytokines production, which is the clinical target for glucocorticoid treatment in glomerular nephritis. In culture condition, MC shows exert several action including the oxygen radical and chemokine production by glucocorticoid or phorbol myristate acetate (PMA) stimulation. According to the modification of MC differentiation; experimental nephritis, immune-complex, EC-SOD production of MC, which is the important for reduction of oxygen radical toxity in extracellular space, was assessed through the cAMP and chemokine production. EC-SOD production of MC was recognized in early stage, and continues to stable in confluent state. The correlation of MC differentiation marker, oxygen radical production oxygenradical scavengers, EC-SOD production was positively correlated with MCs differentiation, negatively correlated with oxygen radical production. Among the ten cases, the glucocorticoid stimulation which induce the stable condition of MC, enhance the both of EC-SOD and cAMP production, suppress the IL-6 and IL-8 production in dose dependent manner. In contrast, PMA stimulation, which induce the activation of mesangial cell, enhance the both of the IL-6 and IL-8 production, suppress the EC-SOD and cAMP production. In unstimulat condition, EC-SOD production was positively correlated with cAMP content, negatively correlated with IL-6 and IL-8 production. The enhancement of the EC-SOD production in MC associate with the promotion of the cAMP production, result in the suppression of IL-6 and IL-8 production, may play the pathophisiological role of glomerular nephritis, suggest the one of the pharmacological activities in glucocorticoid.