活性氧调控可溶性环氧化物水解酶表达增高在门静脉高压症大鼠体内的实验研究

目的?明确活性氧（reactive?oxygen?species，ROS）是否可在肝硬化门静脉高压症大鼠肝外环境中调控可溶性环氧化物水解酶（soluble?epoxide?hydrolase，sEH）表达，验证sEH对这一疾病模型肠系膜血管中肌源性反应的影响。方法?利用多道生物分析仪分别测定正常对照组大鼠、实验对照组大鼠（四氯化碳处理）及NAPDH抑制剂夹竹桃麻素（apocynin，Apo）干预的处理组大鼠门静脉压力；免疫印迹分析3组大鼠肠系膜动脉组织sEH、ROCK及p-moesin蛋白表达水平的变化；血管灌流系统测定各组大鼠肠系膜动脉血管的肌源性反应。多组间均数比较采用单因素方差分析，两两比较采用LSD-t检验。结果?（1）正常对照组、实验对照组和Apo处理组大鼠平均门静脉压力分别为（6.5±0.9）mmHg（1?mm?Hg=0．133?kPa）、（15.9±?1.6）mmHg和（10.6±1.2）mm?Hg，肝硬化门静脉高压症大鼠经Apo处理后，门静脉压力显著降低（P＜0.05）。?（2）与正常对照组比较，实验对照组大鼠肠系膜组织sEH蛋白表达水平明显增高（P＜0.05），p-moesin表达显著降低（P＜0.01），但Apo处理组sEH蛋白表达水平显著降低（P＜0.05），p-moesin表达回复，但仍与正常对照组存在显著差异（P＜0.05）。（3）肌源性收缩在实验对照组大鼠显著降低（P＜0.05），经过Apo干预后，肌源性收缩改善，血管恢复收缩活性。结论?四氯化碳致肝硬化门静脉高压症大鼠肝外环境sEH表达增高，与活性氧含量相关。使用NAPDH特异性抑制剂去除活性氧后，sEH表达减低，血管肌源性反应恢复，提示在肝硬化门静脉高压症中限制sEH作用可作为缓解氧化应激外的另一治疗方向。

Experiment on ROS-induced soluble epoxide hydrolase in rats with portal hypertension

ObjectiveTo investigate the mechanism of reactive oxygen species (ROS) in the regulation of soluble epoxide hydrolase (sEH) in portal hypertensive rats, and to verify the influence of sEH on myogenic response. Methods Portal pressure was measured in normal rats group, carbon tetrachloride treated rats group, as well as rats group treated with NAPDH inhibitor. The protein expression levels of sEH, ROCK and p-moesin in mesenteric arteries tissues of rats in 3 groups were determined by Western-blotting. Myogenic response was detected by vascular perfusion system. All data was analyzed by variance or LSD-t test. Results (1)The portal pressures of the normal control group, experimental control group and Apo-treated group were (6.5±0.9) mmHg, (15.9±1.6) mmHg and (10.6±1.2) mmHg, respectively, with a significant difference among the 3 groups (F=96.5, P<0.05). (2)Compared with the normal control group, the protein expression level of sEH in mesenteric arter-ies of the experimental control group was significantly increased (P<0.05), while it decreased in the Apo-treated group (P<0.05). (3)The myogenic response in portal hypertensive rats was attenuated significantly and revivedafter Apo treatment. Conclusion Apo can reduce the sEH levels in the mesenteric arteries, which suggests that sEH is regulated by ROS. Down-expression of sEH can be the future aim to cure the damaged myogenic response in portal hypertension.