| Background high altitude pulmonary edema(HAPE)is a potentially fatal disease,which is a major cause of death of altitude sickness,It is a rapid?continuous pulmonary edema of non-cardiogenic causes,which is a serious disease.see more at the environment on the plateau to those who have not acclimatization or susceptibility to altitude sickness quickly rose to 2500-3000 meters above within 2-4 days.the incidence of high altitude pulmonary edema was 0.01% at the 2500 meters,at an altitude of 4300 meters,however its incidence increased to(2.5-5)%,if not treated properly will soon lead to the death of the patient,as the prosperity of tourism industry at the plateau and the plateau natural disasters occur frequently,lead to more and more people access to plateau area,so to find a safe and reliable drug is imperative to prevent high altitude pulmonary edema.Objective 1.this experiment by taking coenzyme Q10 In advance,observe the lung wet/dry change,inflammatory factors and the change of oxidative stress in lung tissue homogenate indicators to assess whether coenzyme Q10 have prevention effect of high altitude pulmonary edema and tries to explore its possible mechanism.Method 1.Establishment of high altitude pulmonary edema model 40 male SD rats were randomly divided into four groups:(1)normal control(n=10,normal atmospheric pressure);(2)hypoxia exposure group(n=10,equivalent to 6000 meters altitude),In low pressure oxygen for 1 days;(3)hypoxia exposure group(n=10,equivalent to 6000 meters altitude),In low pressure oxygen for 2 days;(4)hypoxia exposure group(n=10,equivalent to 6000 meters altitude),In low pressure oxygen for 3 days;after anesthesia and then the rats were killed.The ratio of wet to dry ratio of superior lobe of left lung was measured,and the pathological changes lung tissue at different Hypoxia exposure time were observed under HE pathological sections.2.40 male SD rats were randomly divided into 4 group.(1)normal group(n = 10,Normal atmospheric pressure),(2)Hypoxic exposure group(n = 10,6000 altitude),(3)exposed to hypoxia + 30 mg/kg of coenzyme Q10(n = 10,6000 altitude),4.Hypoxic exposure + 10 mg/kg of coenzyme Q10(n = 10,6000 altitude),in the third and the fourth two groups before into the low pressure Yang Cang give dissolve of coenzyme Q10 by 5%cmcc for two consecutive days,stay in low pressure Yang Cang three days later,after anesthesia,Then Kill rats,remove groups of mice lung instantly,the lung tissue after wash with physiological saline,With filter paper blot moisture on the surface of the organization,And the middle and upper lobe of right lung stored at-80 refrigerator,lower lobe lung ?stored at in 10% of the formalin.By using analytical balance determination of normal control group and low oxygen exposure group of superior lobe of left lung water content,calculation of pulmonary edema index,namely lung wet dry weight ratio.we use lower lobe of right lung Made of pathological characterized,then HE color of lower lobe lung and Observe the pathological changes,and the middle and the upper lobe made of tissue homogenate,then measure the change of SOD,MDA,GSH,IL-10,the TNF-a,IL-6,NF-k B.Results 1.Establishment of high altitude pulmonary edema model(1).The success of high altitude pulmonary edema model was mainly to measure the water content in the lung tissue.compared with normal control group 1 days?2 days?3 days hypoxic exposure group,the lung wet to dry ratio was significantly higher(P < 0.01),thus we can establish a SD male rat model of high altitude pulmonary edema.(2).HE staining under the microscope show: compared with normal group,hypoxia group can be observed more leukocyte infiltration in alveolar,and(3 days ?6000m)hypoxia group Telangiectasia was observed in lung tissue.Pink exudate was visible in alveolar cavity.Pulmonary interstitial hyperplasia is also more serious(3).Therefore,the most suitable condition is 6000 m,3 days.2.To explore the protective effect of coenzyme Q10 on pulmonary edema in SD male rats(1).compared with normal control group,hypoxic exposure group lung wet to dry ratio significantly higher(p < 0.01),coenzyme10(30 mg/kg dose and 10 mg/kg dose) Lavage in advance can reduce pulmonary wet dry ratio(p < 0.01),coenzyme Q10 Have certain effect on pulmonary edema.(2).The coenzyme Q10 on SOD?MDA?GSH of SD rat lung homogenate,Compared with normal control group,The SOD levels were lower of hypoxic exposure group(p < 0.01);Before hypoxic exposure we give coenzyme Q10 Continuous lavage for two days.compared with hypoxic exposure group,The SOD level of coenzyme Q10(30 mg/kg dose and 10 mg/kg dose)group significantly increased(p < 0.01),Before hypoxic exposure we give coenzyme Q10 Continuous lavage for two days.,compared with hypoxic exposure group,The GSH level of coenzyme 30 mg/kg Q10 group significantly increased(p<0.05);compared with normal group,lung MDA level in hypoxic exposure group was obviously increased(p < 0.01).Give coenzyme Q10 before hypoxic exposure in rat lung tissue MDA level significantly lower than the merely Hypoxic exposure group(p < 0.01).(3).The coenzyme Q10 have effects on SD rat lung inflammation factors We through ELISA to detect lung tissue inflammation factors of TNF – a?IL – 10 and IL-6.we found in the lung tissue of rats exposed to hypoxia group TNF-a level significantly higher than the normal control group(p < 0.01).after giving coenzyme Q10 begin hypoxic exposure TNF-a level significantly lower than in the lung tissue of purely hypoxia exposure group(p < 0.01).The experiment also confirmed that the pure hypoxic exposure group of IL-10 levels are significantly lower than the normal control group(p<0.01),but after giving coenzyme Q10 30 mg/kg dose begin hypoxic exposure,the level of IL-10 rats group was obviously higher than that of pure hypoxic exposure group(p < 0.01).IL-6 level of hypoxic exposure group was obviously higher than that of normal control group(p < 0.01);Compared with pure hypoxic exposure group,hypoxic exposure before give 30 mg/kg dose of coenzyme Q10 or coenzyme Q10 10mg/kg group,IL-6 level was obviously lower(p < 0.01).(4).The NF-k B expression in Western Blot test we found that pure hypoxic exposure group NF-k B quantity was obviously higher than that of normal control group(p < 0.01);Compared with pure hypoxic exposure group,hypoxic exposure before give 30 mg/kg dose of coenzyme Q10 coenzyme and 10 mg/kg group NF-Kb expression of was obviously lower(p < 0.01).(5).Coenzyme Q10 effects on SD rat lung pathology Lung tissue pathological slices display: compard with normal group,the alveolar of pure hypoxic exposure group have more white blood cells that can be observed in alveolar(p<0.05),and hemorrhage also serious too(P < 0.05),after giving coenzyme Q10 30 mg/kg or 10 mg/kg dose then hypoxic exposure group compared with pure hypoxic exposure group the WBC exudation is lighter.(p < 0.01),.after giving coenzyme Q10 30 mg/kg dose then hypoxic exposure group,Pulmonary edema was obviously lower than that of pure hypoxic exposure group(P < 0.05).Neutrophil infiltration were also lower than those of high altitude hypoxia group(P < 0.05).Conclusion Coenzyme Q10 has protective effect on lung tissue of SD male rats exposed to hypoxia,hypoxia exposure after two consecutive days intragastric administration of coenzyme Q10 can effectively reduce pulmonary edema.and its possible mechanism is by inhibiting inflammation factors and oxidative stress caused by hypoxia to achieve. |
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