The Study Of The Mechanisn Magnesium Prevent And Treat The Radiation Induced Brain Injury By The NF-κB/ICAM-1 Pathway

Part 1:The dynamic change rule of NF-κ B and ICAM-1 due to brain injury in irradiated ratsObjective: To establish the RBI rats model and investigate the dynamic change of the NF-kappa B and ICAM-1 in the injured brain. To research the pathologic mechanism of RBI.Method: Sprague-Dawley rats were randomly divided into two groups, blank control group with sham-irradiation, and irradiation group in which the whole brains of rats were administered by electron beam(5 Me V) to establish the rat model of RBI with the single fractionated dose of 20 Gy. The light microscope histological changes of rats’ brain’ were observed after hematoxylin-eosin(HE)staining. All rats were sacrificed at 1, 3, 7, 14, 28 day post-irradiation respectively. Through the QRT- PCR to detect the m RNA level of the NF-kappa B and ICAM-1 in the brain tissue. The Elisa and Western blot were used to measure the level of NF-κB and ICAM-1 protein in the brain tissue. The NF-κB/ICAM-1protein in positioning expression in the hippocamp was observed via immunohistochemistry(IHC)staining. The ICAM-1 protein in BEC was measured by immunohistochemical,too.Results:(1) The whole brain was irradiated by electron beam total dose of 20 Gy(5 Me V)can establish a model of the RBI.(2) In the irradiation group, the expression of NF-κB m RNA was increased significantly than that of blank control group at 3, 7day post-irradiation respectively.Compared with the blank control group, the expression of ICAM-1 m RNA in the irradiation group was increased significantly at 1, 3, 7day post-irradiation respectively.(3) The overexpression of NF-κB protein was observed at1, 3, 7, 14day(4) post-irradiation, which reached the peak at the 1th day. The expression of ICAM-1 protein in the irradiation group was increased than that of the blank control group at 3,7,14 day post-irradiation respectively.(5) There were positive cells by NF-κB staining in the hippocamp from the first day after irradiation to the 14 th via IHC. There were positive cells by ICAM-1 staining in the hippocamp via IHC,which reached the peak at the 7th day.There were positive cells by ICAM-1 staining in BEC from the first day after irradiation to the end of observation via IHC.Conclusion:Ray can cause the NF-κB/ICAM-1 pathway activation, and the pathway may promote the brain injury development.Part 2:The research of the mechanisn Magnesium prevent and treat the radiation induced brain injury by the NF-κB/ICAM-1 pathwayObjective: Observation the regulatory role of magnesium on NF-κB/ICAM-1pathway activation caused by Ray to explore the mechanisms of magnesium on prevention and cure of RBI.Method: Sprague-Dawley rats were randomly divided into four groups:blank control group(shame-radiation combined with normal saline); experimental control group(radiation combined with normal saline); High-dose treatment group(radiation combined with Mg SO4,500mg/kg weight) and Small-dose treatment grou(radiation combined with Mg SO4,200mg/kg weight). Brain water contents(BWC) were determined by wet/dry weight method. Determination of blood brain barrier integrity with detection brain EB contents.Through the QRT- PCR to detect the m RNA level of the NF-kappa B and ICAM-1 in the brain tissue. The Elisa and Western blot were used to measure the level of NF-κB and ICAM-1 protein in the brain tissue. The NF-κB/ICAM-1 protein in positioning expression in the hippocamp was observed via immunohistochemistry(IHC)staining. The ICAM-1 protein in BEC was measured by immunohistochemical,too.Results:(1) The rats’ weight of experimental group was declined significantly than that of blank control group,but, Mg SO4 treatment against RBI didn’t increased the risk of weight loss.(2) The BWC in experimental group has elevated from the 7th day to the end of(3) observation.The BWC of high-dose treatment group and small-dose treatment grou were declined compared with the blank control group at 7,14,28 days post-irradiation.(4) The content of EB was increased at 1-14 days post-irradiation.The EB content of high-dose treatment group and small-dose treatment grou were declined compared with the blank control group at 1,3,7,14 days post-irradiation.(5) Magnesium can inhibit the expression of NF-κB and ICAM-1 m RNA, and small dose effect is better than that of high dose.(6) Magnesium can inhibit the expression of NF-κB and ICAM-1 protein, and small dose effect is better than that of high dose.(7) Magnesium can reduce the number positive cells by NF-κB/ICAM-1 staining in the hippocamp. Magnesium can reduce the number positive cells by ICAM-1 staining in BEC,also.Conclusion: Mg SO4 can inhibit the NF-κB/ICAM-1 pathway activation, the RBI model of cerebral edema and BBB damage.Mg SO4 can prevent the occurrence of the RBI by inhibit NF-κB/ICAM-1 pathway activation, and small dose inhibition effect is better than that of high doses.