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The Mechanism Of Protective Effect Of Seabuckthorn Seed Oil Fat Emulsion In Mice Against Radiotherapy And Chemotherapy Injury

Posted on:2010-09-30Degree:MasterType:Thesis
Country:ChinaCandidate:L PangFull Text:PDF
GTID:2144360275981067Subject:Pharmacology
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ObjectiveSurgery,radiotherapy and chemotherapy are currently the main means in treatment of tumor.Radiotherapy and chemotherapy play an important role in the treatment of cancer,about 75%of patients will receive radiotherapy and chemotherapy during the course of treatment.However,because of the role of radiotherapy and chemotherapy on tumor cells and normal tissue cells are limited selective,radiotherapy and chemotherapy often leads to normal tissue and cells injury,which is prevalent in clinical.Seabuckthorn seed oil fat emulsion is a new nutritional fat emulsion which physi ological effects,such as,enhanced immunization,anti-tumor,radiation prevention, anti-oxidative and improves the existing fat emulsion for injection ofω-6 andω-3 ratio of undue disadvantage.We work to study the preventative and therapeutic effect of sea buckthorn seed oil fat emulsion on radiotherapy and chemotherapy injury mice and investigate its possible mechanism.Methods1.Seabuckthorn seed oil fat emulsion against radiation injury in miceAccording to the weight,144 Kunming mice,half male and female,were divided randomly into 6 groups.The mice in control group and model group were given intravenous injection with 0.9%saline.And the mice in other groups were dealed with corresponding fat emulsion,dose for 15ml·kg-1·d-1 for 3 days.On the third day,in add- ition to the normal control group,the mice in other groups were given one-time X- ray irradiation(radiation dose:6.0Gy).Then the mice in each group were still dealed with corresponding injection,it last 1,7 or 14 days,respectively.After administeration of drugs,we detected blood and counted the index of thymus and spleen.The cell cycle and apoptosis of bone marrow cell(BMC) were detected by flow cytometer(FCM). The activity of superoxide dismutase(SOD) and monoamine oxidase(MAO) in the gastrointestinal tract of the mice were measured with biochemical method.We limited the food-intake of all mice(6g a mouse) in the course of the whole experiment and weighed each mouse every day.2.Seabuckthorn seed oil fat emulsion against chemoth- erapy injury in miceAccording to the weight,144 Kunming mice,half male and female,were divided randomly into 6 groups.In addition to control group,mice in other groups were given intraperitoneal injection with cyclophosphamide(CTX) for two days,120mg·kg-1·d(-1),to induce the animal model of chemotherapy injury.After model was established,the mice in control group and model group were given intravenous injection with 0.9% saline,and the mice in other groups were dealed with corresponding fat emulsion,dose for 15·kg-1·d-1.It last 1,7 or 14 days,respectively.After administration of drugs,we detected blood and counted the index of thymus and spleen.The cell cycle and apoptosis of BMC were detected by FCM.The activities of SODand MAO in the gastrointestinal tract of the mice were measured with biochemical method.We limited the food-intake of all mice(6g a mouse) in the course of the whole experiment and weighed each mouse every day.Results1.Seabuckthorn seed oil fat emulsion against radiation injury in mice and its possible mechanism.Compared to the control group,mouse the of the model group decreased obviously in weight,thymus gland index,spleen index,WBC,PLT,SOD activity and MAO activity(P<0.05).And the BMC cycle was blocked at G0/G1 phase,and S phase fell off a lot after the model was built,until the 14th day,cell at G0/G1 phase still decreased,but cells at S phase increased a lot and was entering into the multiplication phase(P<0.05).Compared to the model group,weight and food-intake of mouse in high dose and low dose group of seabuckthorn seed oil fat emulsion decreased in a low extent,and recovered earlier;the 7th day after the model was built,spleen index,WBC,PLT,SOD activity,MAO activity and the number of cells at S phase increased remarkably (P<0.05);the 14th day after the model was built,thymus gland index of these two groups was higher(P<0.05).2.Seabuckthorn seed oil fat emulsion against chemotherapy injury in mice and its possible mechanism.Compared to the control group,mouse the of the model group decreased obviously in weight,thymus gland index,spleen index,WBC,PLT,SOD activity and MAO activity(P<0.05).And the BMC cycle was blocked at S phase and G2/M phase(P<0.05), and the cell number in G0/G1 was decreased(P<0.05),until the 14th day after administration,cell at G0/G1 phase still decreased,but cells at G2/M phase were still less(P<0.05).Compared with in model group,the body weight of mice in low and high dose seabuckthorn seed fat emulsion oil group increased,and food-intake of mouse in these groups decreased in a low extent and recovered earlier.The 7th day after administration, WBC,PLT,SOD activity,MAO activity and the number of cells at G0/G1 phase and G2/M phase increased remarkably(P<0.05),and the BMC number of mice in low and high dose seabuckthorn seed fat emulsion oil groups at S phase decreased(P<0.05). The 14th day after administration,the number of cells at G2/M phase in low and high dose seabuckthorn seed fat emulsion oil groups increased remarkably(P<0.05).Conclusion1.Seabuckthorn seed oil fat emulsion can improve myelosuppression caused by radio-therapy. It block the BMC cycle at G0/G1 phase,then mobilized the BMC blocked at G0/G1 phase into S phase,besides there was a preventive effect to the apoptosis in the initial stage of administration.2.Seabuckthorn seed oil fat emulsion can improve the chemotherapy-induced myelosuppression,block the BMC cycle at G0/G1 phase,and promote the BMC that were injured into cell cycle.After long-term drug delivery it could mobilize the BMC blocked at G0/G1 phase into cell cycle,increase the cell number in G2/M phase;and seabuckthorn seed oil fat emulsion can reduce chemotherapy-induced apoptosis of bone marrow cells.3.Seabuckthorn seed oil fat emulsion can decrease the release of 5-HT in gastro intestinal tract and accelerate the degradation of 5-HT by enhancing the activity of SOD and MAO.Therefore Seabuckthorn seed oil fat emulsion can improve gastrointestinal reactions caused by radiotherapy and chemotherapy.
Keywords/Search Tags:seabuckthorn seed oil fat emulsion, radiotherapy Injury, chemotherapy Injury, protective effect
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