一氧化氮对高热惊厥大鼠海马血红素氧合酶/一氧化碳体系的影响

目的　研究一氧化氮合酶(NOS)抑制剂Nω硝基L 精氨酸甲酯(L-NAME)对反复高热惊厥(FS)大鼠海马血红素氧合酶1(HO- 1)mRNA和蛋白表达及一氧化碳(CO)含量的影响,以探讨一氧化氮(NO)对HO/CO体系的调节作用。方法　采用热水浴诱导大鼠FS。将发育期大鼠随机分为3组:对照组,FS组和FS+L- NAME组。分光光度计间接测定血浆NO和CO含量;核酸原位杂交法检测海马神经元HO- 1mRNA表达;Western印迹方法检测海马神经元HO -1蛋白含量。结果　与对照组比较,反复FS后海马神经元HO -1mRNA表达明显增高,HO -1蛋白含量升高208% (P<0 .01),血浆CO含量增高94 .57% (P<0. 01)。用L NAME干预FS,血浆NO含量下降13 79% (P<0. 05),海马HO 1mRNA表达明显下降,HO .1蛋白表达下降30 .19% (P<0 .01),血浆CO含量下降16 14% (P<0. 05)。结论　反复FS时,外源性给予NOS抑制剂可降低NO含量,同时引起HO 1的基因表达及CO含量下降。

Influence of nitric oxide on heme oxygenase/carbon monoxide system in hippocampus of febrile seizures rats

OBJECTIVE: Febrile seizures (FS) are the most common type of seizure disorders. Studies have found that there have respective changes of heme oxygenase (HO)/CO system and nitric oxide synthase (NOS)/NO system during FS. The present study was to explore the influence on expression of HO-1 mRNA and protein and content of CO after recurrent FS by NOS inhibitor N(omega)-nitro-L-arginine Methyl ester (L-NAME), in order to demonstrate a regulating role in HO/CO system by NO. METHODS: Forty-eight SD rats were randomly divided into 3 equal groups: FS group, undergoing intraperitoneal injection of normal saline (NS) and then bath in 45.2 degrees C hot water for 5 minutes every other day for 10 times, FS + L-NAME group, undergoing intraperitoneal injection of NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) and then FS for 10 times, and control group, undergoing intraperitoneal injection of NS and then bath in 37.0 degrees C water. Twenty-four hours after the last bath blood was collected from the abdominal cardinal vein to measure the concentrations of plasma nitric oxide and carbon monoxide with spectrophotometer. The brains were taken out to be made into frozen slices to undergo HO-1 in situ hybridization to measure the mRNA expression of HO-1. The hippocampus was taken out to undergo Western blotting to measure the expression of HO-1 protein. RESULTS: The plasma CO concentration was higher by 94.5% in the FS group in comparison with that in the control group (P < 0.01). The plasma CO concentration of the FS + L-NAME group was higher by 63.18% than that of the control group (P < 0.05) and lower by 16.14% than in the FS group (P < 0.05). The HO-1 mRNA expression was significantly higher in the FS group than in the control group. The HO-1 mRNA expression of the in hippocampal neurons of the L-NAME was lower than that of the FS group, however, still higher than that of the control group. Western blotting showed that HO-1 protein was expressed in all 3 groups; the HO-1 protein expression of the FS group was higher by 208% than that of the control group; and the HO-1 protein expression of the FS + L-NAME group was higher by 115% than that of the control group (P < 0.01) and lower by 30.19% than that of the FS group (P < 0.01).