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Objective:To evaluate the prevention effect of low dose pre-irradiation on irradiation-induced lung injury and its possible mechanism.Methods:Totally 320 6-week-old female C57BL/6j mice were divided into control (0 Gy), low-dose (0.5 Gy), high-dose (20 Gy) and low-dose pre-radiation(0.5 Gy+ 20 Gy)groups by the random number method, with 80 mice in each group. The mice in the low-dose and low-dose pre-irradiation groups were placed in the immobilization device under full consciousness and subjected to 0.5 Gy X-ray whole-body irradiation. 2 weeks later, the 0.5 Gy pre-irradiated mice were anesthetized and subjected to 20 Gy X-rays on chest, as the pre-radiation plus high dose radiation group. The mice in the control group were irradiated with mock irradiation (0 Gy). All mice were terminated at designed time points (24 h, 1 month, 3 months and 5 months) after completion of the irradiation schedule, with 20 mice/group at each time point. Then, lung tissues were taken from mice, and pathological changes were observed by hematoxylin-eosin (HE) staining and Masson′s trichrome staining. RT-qPCR and Western blot were used to detect the expressions of mRNAs and proteins of pulmonary fibrosis-related factors.Results:Pathological changes were observed in the lung tissues 1 month after a single high-dose 20 Gy irradiation, mainly including radiation pneumonitis and a small amount of collagen accumulation, which was more serious than low-dose pre-irradiation group, and these pathological changes became more severe when the time after irradiation increased. Meanwhile, the mRNA and protein levels of proSP-C and HOPX in the low-dose pre-irradiation group were higher than those in the high-dose group, except for proSP-C protein expression at 3 and 5 months post-irradiation. A more significant change was that the mRNA level of TGF-β1 in the high-dose group was 5.8-13.6 times higher than that in the other groups at 5 months after irradiation, as well as β-catenin mRNA ( t=4.22, 5.11, P<0.05). At the same time, in the early period (24 h and 1 month) post-irradiation, the level of vimentin protein in the low-dose pre-irradiation group was significantly higher than that in the high-dose group ( t=6.54, 4.28, P<0.05). Conclusions:When the mice were pre-irradiated with 0.5 Gy X-rays, an adaptive protective response was induced in lung tissues, resulting in the tolerance to subsequent high dose irradiation.
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Objective To identify the association of thyroid stimulating hormone receptor ( TSHR ) gene intron 1 susceptible loci and 4p14 susceptible locus rs6832151 polymorphisms with Graves’ disease ( GD) in Han Chinese population in Bengbu, Anhui, China. The gene-gene interaction among TSHR intron 1 susceptible loci and 4p14 susceptible locus rs6832151 was also investigated. Methods The genotypes of the single-nucleotide polymorphisms ( SNPs) were analyzed by Taqman probe technique on Fluidigm EP1 platform in 611 patients with GD and 555 control subjects, and linkage analysis, correlation analysis, haplotype analysis, and epistasis analysis with them were performed. Results Six SNPs in two candidate genes(rs12101261, rs4903964,rs179247, rs2284722 and rs17111394 in TSHR, rs6832151 in 4p14) were associated with GD (all P<0. 05). The frequency distributions of haplotypes of SNPs in TSHR intron 1 ( AGTA, GGCG, AATA, and CC) were significantly different between GD and control groups(all P<0. 01). There existed the interactions between rs179247 and rs12101261 in TSHR(P=0. 001) and among rs179247(TSHR),rs4903964(TSHR) and rs6832151(4p14) (P=0. 001). Conclusions rs683215 in 14p14 and rs12101261, rs4903964, rs179247, rs2284722 and rs17111394 in TSHR intron 1 were susceptible loci of GD in the Chinese Han population from Bengbu. The haplotypes in TSHR intron 1 were associated with GD. There exists the interaction between the SNPs in TSHR and 4p14,which may change the risk of GD.
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[Summary] The genotypes of rs6832151 in the 4p14 were genotyped by Taqman probe technique on FluidigmEPl platform in 617 patients with Graves′disease( GD) and 4 915 health control subjects. The result showed thatRs6832151 Gin4p14wasstronglyassociatedwithGD(OR=1.39,P0. 05). The result suggests that rs6832151 G in 4p14 is the susceptibility genes of Graves′ disease in Bengbu population, and is related to the high risk of GD.
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Aim To establish method and main evaluation indexes of collagen induced arthritis ( CIA) model in DBA/1 mice. Methods CIA was induced by chicken type Ⅱcollagen ( C Ⅱ) in DBA/1mice. Arthritis was evaluated by arthritis index. X-ray of the paws was taken. Histology pathology of ankles and spleen was observed and scored. Results Immunization d31,the paws of CIA mice appeared red and swelling,the scores of arthritis index increased,the period of swelling peak was from d40 to d60; immunization d35,the weight of CIA mice began to decrease. X-ray of paws showed that the paw joints of CIA mice deformed,and there was osteophyte formation associated with osteolysis. Histo-logical pathology of ankle joints showed that the synovium of CIA mice were hyperplasia,cartilage was destroyed,pannus was formed,and inflammatory cells infiltrated into synovium. Histological pathology of spleen showed more germinal centers and lymphoid follicular hyperplasia were observed,cell density of lymphatic sheath increased,scores of ankle joints and spleen histological pathology in CIA mice were higher than those in normal mice significantly. Conclusions The methods of CIA model induced by chicken C Ⅱ in DBA /1 mouse were reliable and reproducible. CIA incidence was high. Arthritis index,X-ray of paws,ankle joints and spleen histological pathology and so on were the principal indexes of evaluation for CIA model.