罗痛定对脑缺血/再灌注损伤大鼠器官组织一氧化氮合酶的影响

Effects of rotundine injection on nitric oxide synthase in tissues of different organs after ischemia/ reperfusion of brain in rats

目的观察大鼠脑缺血/再灌注（I/R）损伤不同阶段肺、肝、肾组织一氧化氮合酶（NOS）的活性变化,探讨罗痛定的作用机制。方法选择76只SD大鼠,按改良的四血管阻塞法建立脑I/R损伤模型。随机分为假手术组、I/R损伤组和罗痛定治疗组,后两组分别于再灌注2、6、12、24和48h处死大鼠,测定肺、肝、肾组织不同类型NOS活性。结果I/R损伤组总NOS（tNOS）活性于再灌注2、12和24h均较假手术组显著升高（P〈0.05或P〈0.01）,尤以12h时上升最显著（P均〈0.01）;2h时以结构型NOS（cNOS）活性上升为主（P均〈0.05）;12h时以诱生型NOS（iNOS）活性上升为主（P均〈0.01）,至24h仍较高（P均〈0.05）,48h时基本接近假手术组水平。与I/R损伤组比较,罗痛定治疗组各组织cNOS活性在2h时上升更显著（P均〈0.05）,iNOS在12h以后明显下降（P〈0.05或P〈0.01）。结论在脑I/R损伤不同阶段肺、肝、肾组织中不同类型NOS活性不同,发挥作用不同;罗痛定可以通过调节不同类型NOS活性减轻组织损伤。

Objective To explore the protective effect of rotundine injection on lung, liver and kidney damages after cerebral ischemia/reperfusion （I/R） injury in rats based on the activity changes of nitric oxide synthase （NOS）. Methods Seventy- six rats were randomly divided into three groups： sham operation group, I/R injury group and treatment group, and determinations were done at five different time points. The cerebral I/R models were reproduced by improved 4 vessels occlusion method. The activities of NOS in the lung, liver and kidney were measured in all the rats at 2, 6, 12, 24 and 48 hours after reperfusion. Results Compared with sham operation group, the activities of total NOS （tNOS） were significantly increased at 2, 12 and 24 hours in I/R injury group （P〈0.05 or P〈0.01）, with the peak value at 12 hours （all P〈0.01）. The activities of constitutive NOS （cNOS） were increased significantly at 2 hours （all P〈 0.05）, and those of induced NOS （iNOS） were increased at 12 hours （all P〈0.01）. The activities of iNOS were still high at 24 hours （all P〈0.05）, and approached the levels of sham operation group at 48 hours. Compared with I/R injury group, the activities of cNOS in various organs increased much higher at 2 hours in treatment group （all P〈0.05）. But those of iNOS were significantly decreased after 12 hours （P〈0.05 or P〈0.01）. Conclusion The various types of NOS play different roles in the lung damages after brain I/R injury at different stages in rats. Rotundine injection can ameliorate the damages by modulating the activities of different types of NOS.