Changes of free radicals and nitric oxide synthase in rat brain following ischemia-reperfusion injury due to different dosage brain-awakening nasal sprayer intervention / 中国组织工程研究

ABSTRACT

BACKGROUND: Brain-awakening nasal sprayer is composed of many herbs,such as Chuanxiong and Shichangpu, which were regarded by "Shennong Bencaojing" as having the function of "preventing stroke in the brain".OBJECTIVE: To observe the changes of free radicals and nitric oxide synthase in rat brain following focal ischemic-reperfusional injury due to brain-awakening nasal sprayer intervention and compare with that due to classical nimodipine.DESIGN: A randomized controlled study.SETTING: Department of internal medicine of a hospital affiliated to a traditional Chinese medical university.MATERIALS Seventy adult male Wistar rats of clean grade, were randomly divided into seven groups brain-awakening nasal sprayer of higher dosage group, moderate dosage group, lower dosage group, nimodipine intraperitoneal injection group, physical saline nasal sprayer group, menstruum nasal sprayer group, and sham operation group with 10 rats in each.METHODS: Focal brain ischemia-reperfusion model was established by blocking the left cerebral middle artery in rats of all the groups except sham operation group. Three days before model establishment and during reperfusion, rats were given different dosages of brain-awakening nasal sprayer composed of Chuanxiongqin and Shichangpu of 5.4, 2.7, 1.08 mg/(kg · d) and 1.35, 0. 54, 0.27 g/(kg· d), respectively, three times a day; which was replaced by physical saline and menstruum nasal sprayer of 0. 18 mL/ (kg · d),three times a day in physical saline nasal sprayer group and menstruum nasal sprayer group; rats in nimodipine intraperitoneal injection group received intraperitoneal injection of nimodipine by 0. 8 mg/(kg · d) twice a day. Rats in sham operation group were routinely raised. The content of prodialdehyde, superoxide dismutase and nitric oxide synthase were measured with colorimetric method.MAIN OUTCOME MEASURES: ① The changes of prodialdehyde content, superoxide dismutase and nitric oxide synthase activity in rat brain following focal ischemic-reperfusional injury in groups of different dosage of brain-awakening nasal sprayer and other groups. ② Comparison between different dosage brain-awakening nasal sprayer intervention groups and nimodipine intraperitoneal injection group.RESULTS: Eight rats died during model establishment and the other 62 rats entered the results analysis. ① Content of prodialdehyde It was significantly lower in higher dosage group and nimodipine intraperitoneal injection group than in physical saline nasal sprayer group [ (0.92 ± 0. 32), (0. 87 ± 0. 39)vs(1.35 ±0. 34) μmol/g, P ＜ 0.05], but there was no difference between higher dosage group and nimodipine intraperitoneal injection group. ② Activity of superoxide dismutase It was obviously higher in higher dosage group and nimodipine intraperitoneal injection group than in physical saline nasal sprayer group[ (35.64 ± 11.67), (33.88 ± 7. 15) vs(20. 70 ± 3.88) NU/mg,P ＜ 0. 05 ], but no difference could be observed between higher dosage group and nimodipine intraperitoneal injection group. ③ Activity of nitric oxide synthase and superoxide dismutase It was found obviously higher in higher dosage group and nimodipine intraperitoneal injection group than in physical saline nasal sprayer group[ (4.64 ± 1.22), (5.00 ± 1.10) vs (3.08 ± 1.12) mkat/g, P ＜ 0.05], but no difference could be observed between higher dosage group and nimodipine intraperitoneal injection group.④ The activity of nitric oxide synthase and superoxide dismutase slightly increased while prodialdehyde slightly decreased in moderate dosage group,lower dosage group and menstruum nasal sprayer group, which did not differ significantly from physical saline nasal sprayer group.CONCLUSION: Brain-awakening nasal sprayer intervention exerts multiple effects such as preventing lipo-peroxidation following brain ischemic- reperfusional injury, in addition to suppressing prodialdehyde production, attenuating injury induced by free radicals and increasing nitric oxide synthase activity, thereby playing a similar role to nimodipine in protecting against brain ischemic-reperfusionaldamage