| Objective: Most of the effectiveness and the safety evaluation of the drug take the adult and adult animals as objects, in the drug development process. However, the efficacy and side effects varied due to the age difference. Hematopoietic system sensitived to the foreign objects including drugs. The immune system injury reactivity are different between elderly and adult. Cyclophosphamide is a widely used immunosuppressive agent, which has been used in this study to evaluate the difference of the recovery of hematopoietic system damage between aged mice and adult mice to provide a reference for clinical medication for children and elderly.Methods: 32 male C57BL/6 mice of different age include 12 in the control group,20 in the cyclophosphamide group. Juvenile, adult and elderly mice is 21 days old, 8weeks old, 14 months old respectively. Adult mice, elderly mice were treated with cyclophosphamide 100mg/kg by intraperitoneal injection(first treatment at d1, second treatment at d3, 50mg/kg). Juvenile mice were treated with cyclophosphamide 72mg/kg by i.p. with the equivalent dose(36mg/kg, first treatment at d1, second treatment at d3respectively) and the control mice were treated with saline in the same way as the cyclophosphamide treated mice. The weight of mice with different age, the indexes of immune organs, etc, were measured in 3, 7, 14, 28 days after treatment.Results:(1) Compared with the adult mice, the thymus index of juvenile mice, the proportion of HSC and spleen Treg cells were significantly higher than adult mice(P<0.05); juvenile mice CFU-GM, the proportion of thymic CD4+T, CD8+T cells and spleen B cells were significantly lower than adult mice(P <0.05). The WBC of elderly mice, the proportion of neutrophil, the weight, BMNCs, CFU-GM, the proportion of HPC, peripheral blood NK cells, macrophages were significantly higher than the adult mice's(P <0.05); elderly mice's proportion of lymphocyte, thymus index, the proportion of HSC, thymic CD4+T, CD8+T, CD4+TCD8+T cells, splenic B cells, and Treg cells,the number of peripheral blood CD4+T were significantly lower than adult mice(P<0.05)(2) after treatment, the proportion of juvenile mice's thymic CD4+T cell didn't show significant change; thymus CD8+T cells, CD4+TCD8+T lymphocytes had better prognosis; spleen Treg cells had poor prognosis; CFU-GM was damaged seriously with poor prognosis. HPC proportion of elderly mice didn't show obvious change; HSC injury was more serious; peripheral blood NK cells, B cells, macrophages, CD4+T cells had poor prognosis; the number of leukocytes, neutrophils, spleen index injury were more serious and they had poor prognosis.Conclusion: Compared with adult mice, the hematopoietic immune system of juvenile mice is not perfect, but the hematopoietic ability of bone marrow is high.Elderly mice's function of hematopoietic immune system gradually degrade. The juvenile and elderly mice's whole hematopoietic immune system are weaker than the adult mice. After treatment with cyclophosphamide, juvenile and elderly mice's situation of hematopoietic system damage, recovery are consistent with the adult mice,suggesting that cyclophosphamide has no obvious influence on the damage and recovery of hematopoietic system of mice with all ages. Juvenile mice's situation of immune system damage, recovery are consistent with the adult mice's. The immune system of elderly mice is more sensitive than adult mice. It shows that compared with the adult mice, immune system damage indued by cyclophosphamide in elderly mice is more severe.Objective:The incidence of cancer continues to rise and the trend was younger, in modern society. Clinical treatments are surgery, chemotherapy,radiation therapy and targeted therapy. About 70% of cancer patients in need of more clinical radiotherapy. Radiotherapy for killing cancer cells but also normal cells caused by radiation damage. After radiation injury of hematopoietic and immune function, slow recovery is one of the most serious side effects of radiotherapy. Children and the elderly hematopoietic immune system is more sensitive than the young adults. This study was on irradiation of mice at different ages(young mice, adult mice,aged mice) and injury recovery of the immune system, to explore young mice,according to the difference in reactivity after blood and immune system by adult mice aged mices, for children, the elderly provide a reference radiation protection.Methods: 40 male C57BL/6 mice of different age include 20 in 2Gy irradiation group, 20 in 4Gy irradiation group. Juvenile, adult and elderly mice is 21 days old, 8 weeks old, 14 months old respectively.Different age mice treated with 137 cesium source irradiator irradiation dose micee of 0.873 Gy / min. The weight of mice with different age, the indexes of immune organs, etc, were measured in 3, 7, 14, 28 days after treatment.Results: After irradiated, the majority of all age indicator the first three days of mice acute inhibition in a dose-dependent manner. 1) WBC:adult mices on the third day to a minimum value and a dose-dependent manner.2Gy accessible in 7 days to restore normal, 4Gy after nearly four weeks to restore normal. Compared to adult mice, young mice heavier injury,senile mice injured heavier and can not be restored after 4 weeks. 2) WBC:NE%: irradiated adult mice after the first three days rose to the highest value in a dose-dependent manner. 2Gy group returned to normal after 4weeks, 4Gy group four weeks is still not returned to normal levels. Ly%:irradiated adult mice after the first three days to a minimum value, and a dose-dependent manner. 2Gy group, 4Gy group were in seven days, two weeks after the return to normal. Compared to adult mice, 2Gy group of young mices, aged mices lymphocyte miceio substantially unchanged. 4Gy group and the repair of damage similar to adult mices. 3) thymus index: adult mice 2Gy, 4Gy irradiated group on the third day decreased to the lowest value and the consistent recovery situation four weeks. Young mice damage and recovery trends and adult mices similar. Aged mices 2Gy, 4Gy after irradiation to the first four weeks did not change significantly. 4)thymocytes type: adult mouse CD4 + T, CD8 + T, CD4 + CD8 + T decreased to as low a dose dependent manner in the first 3 days, 7 days return to normal. Changes in juvenile mices and adult mices are basically the same trend. Compared with adult mices, aged mices CD4 + T, CD8 + T, CD4 + CD8+ T heavier damage and the prognosis is poor. 5) spleen index: adult mice2 Gy, 4Gy irradiation group to minimize the value of the third world a dose dependent manner, respectively, in 7 days, 4 weeks this returned to normal levels. Changes in juvenile mices and adult mices similar trend.After the aged mices 2Gy irradiation damages and recovery similar to adult mices, but the prognosis is poor 4Gy irradiation. 6) spleen cells type:two adult mice irradiated group B cells, Treg cells reached the lowest value in the first seven days, a dose-dependent manner, and 4 weeks return to normal, but 4Gy group B cells with poor prognosis. 7) bone marrow cell type and function test: After irradiated, the number of adult mices with unilateral femoral, HSC, HPC, CFU-GM values were dose-dependent manner in the third world to a minimum. 4 indicators can resume normal at 4 weeks.Compared to adult mice, young mice unilateral femoral lesion count more heavy and slow recovery. Aged mice HSC, CFU-GM 4 weeks still unable to resume normal.Conclusion: After irradiated, most indicators of adult mouse hematopoietic system, immune system in the first three days of acute inhibition in a dose-dependent. After 3 days of injury recovery to 4 weeks to resume most normal indicators, 2Gy irradiated group than 4Gy recovery group. Compared to adult mice, young mice hematopoietic immune system to be more sensitive to radiation in a dose-dependent manner, the impact of which is particularly evident on the hematopoietic system. Aged mices blood, the immune system are more sensitive to radiation in a dose-dependent manner, suggesting that, compared with adults, children sublethal doses of radiation hematopoietic system, immune system, affect the elderly hematopoietic heavier. |
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