| BackgroundWith the development of science and technology, more and more applications of nuclear power involves the field of military, scientific research, medical and industrial production, which makes people come into contact with a substantially increased risk of ionizing radiation environment, and when the dose more than 1 Gy in short time, it will cause serious damage to the body -- acute radiation injury (ARI). Now the era of peace, in spite of all countries to resist nuclear weapons in combat application, but it’s also seen by the side effect of radiotherapy, nuclear energy leakage, industrial radiography source loss of acute radiation injury. Therefore, strengthening the measures of prevention and treatment of acute radiation injury has become a priority among priorities.Therefore, we want to get an effective safe and non-toxic drug to prevent from radiation.It is to improve physical quality in patients with radiotherapy and someone who may approach to irradiation. Traditional Chinese herbs are our country medical characteristics. A lot of research has proved that traditional Chinese medicine has exact effect against radiation injury.But ARI is emergent disease which results in the progress of science and technology, which TCM has a little description. To study the clinical symptoms of ARI, we think that the pathogen is similar to "duxie" in traditional Chinese medicine, but there is some spects different. We study it with "duxie" of TCM theory, which may rich the theory of TCM in researching ARI. Therefore, we made Husui Fukang Yin to prevent and treat ARI. We would explore radioprotective effect of Husui Fukang Yin through the experimental study. ObjectiveWe want to investigate the etiology of ARI from the perspective of "duxie", and to determine the radiation-protecting agent of TCM theory for protecting our body from ARI. We would explore radioprotective effect of Husui Fukang Yin through the experimental study, in order to enrich the theory of TCM in protecting our body from ARI. Finally, we wish that we found safe and effective drugs to prevent ARI. Method Theoretical study:The theory of "duxie" in traditional Chinese medicine origin to literatures, and the types and characteristics of "duxie" should be summarized. Compare with "duxie",we should study the clinical symptoms of ARI. Compare with several kinds of "duxie". we should manifest IR is a kind of "duxie".Experimental study:Part 1:Screening of effective Chinese herbal fomular to protect from ARI.Experiment 1:The animal models of ARI were replicated the male Kunming mice.There are five groups including Contral group, Acute radiation injury group(ARI), ARI with high dose of Guiqi decoction group, ARI with middle dose of Guiqi decoction group, ARI with low dose of Guiqi decoction group. Mice of Contral and ARI were treated with water, while the others were administered with the above medicines respectively for 22 days. In the 8th day by treated,mice except Ctrl group were irradiated by 4 Gy 60Co.In the 14 day after radiation, white blood cell were counted, thymus and spleen index were weighed and calculated, SOD activity and MDA content were detected.Experiment 2:The animal models of ARI were replicated the male Kunming mice.There are five groups including Contral group, Acute radiation injury group(ARI), ARI with No.1 decoction group, ARI with No.2 decoction group, ARI with No.3 decoction group. Mice of Contral and ARI were treated with water, while the others were administered with the above medicines respectively for 16 days. In the 15th day by treated, mice except Ctrl group were irradiated by 5 Gy 60Co.In the 24 hour after radiation, some relevant indicators would be detected to find an effective decoction to protect from IR.Part 2:Study on protective effects and mechanism of Husui Fukang Yin on acute radiation injury in miceThe animal models of ARI were replicated the male Kunming mice.There are six groups including Contral group (Ctrl), Acute radiation injury group(ARI), ARI with high dose of Husui Fukang Yin group (ARI+H), ARI with low dose of Husui Fukang Yin group (ARI+L), ARI with Amifostine group (ARI+Am) and ARI with Anduolin group (ARI+An). Mice of Ctrl and ARI were treated with water, while the others were administered with the above medicines respectively for 14 days. Then, except Ctrl group, mice in other groups were irradiated by 4 Gy 60Co.Experiment 1:In 3rd,7th, and 10th day, orgens index should be calculated, WBC and LY should be counted, pathological changes of spleen should be made, and the ratio of CD4+/CD8+T lymphocyte of peripheral blood should be calculated.Experiment 2:In 3rd,7th, and 10th day, RBC, HGB, PLT should be counted, pathological changes of bone marrow should be made, and SOD activity and MDA content of liver should be detected.Experiment 3:In third day after radiation, the level of TLR-9, TNF-α, IL-4 in spleen was detected.ResultTheoretical study:The etiology of ARI is ionizing radiation. IR is not related in the traditional theory of T C M.Someone analysis the similarities and differences between "Huoxie" and IR.But we think that IR is a kind of "duxie". We want to improve the treatment of ARI, and lay a theoretical foundation for the prevention of traditional Chinese medicine.Experimental study:Part 1:Screening of effective Chinese herbal fomular to protect from acute radiation injury.1. Preliminary study of Guiqi decoction on the ARI mice:In 14th day after radiation, the count of white and red blood cell and spleen index in ARI group decreased significantly. Low dose of Guiqi decoction could promote WBC, RBC and spleen index, it also has a function of antioxidation.2. Study on screening of traditional Chinese medicine formula in prevention of ARI:In 24 hour after radiation, the count of WBC, LY, HGB, PLT and immune orgen indexes in ARI group decreased significantly, obvious pathological changes could be occered in bone marrow. No.3 decoction could promote PLT and lighten pathological changes in bone marrow. In the 14th day by treated, No.3 and No.1 decoction could induce the content of TG.These decoction had little influence in peripheral blood cell count and immune orgen indexes.Part 2:Study on protective effects and mechanism of Husui Fukang Yin on acute radiation injury in mice1 Effects of Husui Fukang Yin and/or ionizing radiation on immune system of mice:1) Body weight showed a slow growth trend. In 1st day after radiation, the weight of the ARI was significantly decreased after exposure.2) In 3rd day after the radiation, there is no difference between Ctrl with ARI. In 3rd day after radiation, the thymus and spleen index of ARI decreased rapidly. Until to the 10th day after radiation, although these indexes increased, but they were not restored to the normal level.Low dose of Husui Fukang Yin can recovery index of immune organs of mice after radiation.3) In 3rd day after radiation, WBC, LY of ARI decreased rapidly. Until to the 10th day, peripheral blood cell number is still at a very low level.4) In 3rd day after irradiation, the ratio of CD4+/CD8+ in ARI increased significantly. Until to the 10th day, the ratio of ARI has no difference with Ctrl. Husui Fukang Yin can reduce the ratio of CD4+/CD8+5) In 3rd day after radiation, obvious pathological changes could be occered in spleen.The volume and function of spleen reduced significantly. Splenic corpuscle structure was disordered and atrophied obviously.Lymphopenia appeared. Splenic trabecular density reduced.The red pulp cords narrowed.Splenic sinus was to be congestion. There could be neutrophil infiltration in spleen. In 7th and 10th day after radiation, pathological changes of spleen reduced in model group. Husui Fukang Yin can reduce spleen pathological change after irradiation. 2 Effects of Husui Fukang Yin and/or ionizing radiation on hematopoietic system and oxidative stress of mice:1) In 3rd day after radiation, PLT and HGB of ARI decreased rapidly. In 7th day after radiation, RBC of ARI began to decline. Until to the 10th day, peripheral blood cell number is still at a very low level. Low dose of Husui Fukang Yin had antagonistic action on reducing PLT.2) In 3rd day after radiation, obvious pathological changes could be occered in bone marrow. Bone marrow hyperplasia decreases extremely. In 7th and 10th day after radiation, pathological changes of bone marrow reduced in model group. Husui Fukang Yin can reduce bone marrow pathological change after radiation.5) In 3rd day after radiation, the activity of SOD in ARI reduced unusually, and MDA content elevated suddently. In 7th day after radiation, the SOD and MDA returned to the normal level.Low dose of Husui Fukang Yin could elevate the activity of SOD, and reduce the content of MDA after radiation.3 Gene expressions of Husui Fukang Yin and/or ionizing radiation on mice spleen in 3rd day after irradiation:The expression of TLR-9 and TNF-a in ARI were significantly increased. There might be not obvious changes in IL-4 levels. Low dose of Husui Fukang Yin can be antagonistic cytokine.ConclusionTheoretical research:To analysis of the cause of ARI from "duxie", we think that IR is a kind of "duxie". We want to improve the therapy of ARI, and lay a theoretical foundation for the prevention of TCM.We made Husui Fukang Yin to prevent from acute radiation injury, which has functions of detoxicating and tonifying qi and yin.Experimental study:Our experiment successfully replicated the experimental animal model of ARI, and screened the potential formula of No.3 decoction to prevent from ARI. Then, we carry on the optimization to a new formula, named as Husui Fukang Yin. Low dose of Husui Fukang Yin has a protective effect on ARI mice, and its mechanism may be related to regulating the expression of related cytokines. |
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