| BackgroundThe area above 2500 m above sea level is called the plateau in medical sense.The area of the plateau in China accounts for more than 33% of the total land area,and there is a long border on the plateau.Due to the high terrain with thin air,low oxygen partial pressure,ultraviolet light,cold and other climatic characteristics.With the implementation of the western development strategy,more and more people enter the plateau to work,study,travel and live.After entering the plateau,the human body will cause headaches,fatigue and other acute altitude reactions.Usually,people will adapt to the plateau environment through a series of compensatory reactions.When the population in the plain region enters the plateau environment,the body gradually ADAPTS to the anoxic environment through the establishment of anoxic adaptation mechanism.After entering the plateau,most people establish a series of hypoxia-acclimatization mechanisms in a few days or weeks,so that the internal metabolic level of the body is unified with the external environment,gradually adapt to the hypoxia environment on the plateau,and achieve full acclimatization.However,about 10% of the population still fail to achieve effective adaptation after a period of practice,resulting in the occurrence of chronic plateau disease,which has a certain impact on the health and safety of the newly entering the plateau population.Therefore,the study of the effects of the low-oxygen environment on the body of the plateau will be beneficial to the health of the population living in the plateau and the increasing number of migrant population,and has far-reaching practical significance for expanding the living space of human beings and the economic development of the plateau region.Studies have shown that hypoxia can disrupt homeostasis in the body's environment,especially if the embryo is stimulated by prolonged hypoxia,which can lead to a variety of abnormalities and diseases,including Congenital Heart Disease(CHD).CHD is a disease of the heart caused by the formation of the heart and large blood vessels during human embryonic development(within the first 2-3 months of pregnancy),or by the failure to close the automatically closed channels after birth(which is normal in the fetus).At present,it is generally believed that it is the result of the interaction between environmental factors and genetic factors.CHD is so harmful that about one-third of all children die within one month of birth if not diagnosed and treated promptly and accurately.It is one of the most common birth defects in the world and the leading cause of death in infants and young children.Long-term exposure of pregnant women to highaltitude environments will lead to long-term chronic hypoxia in the fetus,and intrauterine hypoxia is a very important inducement for CHD.It is of great theoretical and practical value to study the prevention and treatment of cardiopulmonary and other diseases of plateau hypoxia.A great deal of research has been done on the mechanism of hypoxia adaptation at the molecular,cellular and tissue levels.With the development of molecular biology,protein and gene changes under hypoxia have been paid more and more attention.The pathogenesis of altitude disease and the material basis of hypoxia adaptation have become the new focus of life science research.Micro RNA(miRNA)is a kind of non-coding endogenous small single-stranded RNA molecule with a degree of about 22 nucleotides newly discovered in scientific research work.It is a post-transcriptional regulator of gene expression,whose main function is to induce target gene silencing.Only 3 percent of the human genome codes for proteins,and a number of studies have now found that the rest is now widely transcribed.A single micro RNA has been shown to regulate the expression of multiple genes.In contrast,the expression of a single gene can be regulated by multiple mirnas.Micro RNA and target m RNA form incomplete complementary pairing,so a micro RNA can have multiple targeted genes,and multiple micrornas can jointly regulate the same target genes,forming a precise and complex regulatory network in the human body.Therefore,the misexpression of one micro RNA in the organism can lead to the misexpression of a large number of proteins.More and more studies have found that micrornas are involved in the regulation of many important biological processes,such as growth and development,cell apoptosis,cell proliferation,angiogenesis and proliferation.The expression of a specific micro RNA depends largely on the type of tissue and cell,the body's metabolism,and the state of the disease.Since the discovery of micro RNA in blood circulation,they have been widely studied by domestic and foreign scholars as new biomarkers,mainly focusing on the function and mechanism of micro RNA and the correlation between micro RNA and disease.A large body of evidence suggests that micrornas play a role in the pathogenesis of many cardiovascular diseases and have been identified as key regulators of complex biological processes associated with a variety of cardiovascular diseases,including left ventricular hypertrophy,ischemic heart disease,heart failure,hypertension,and arrhythmias.Micro RNA has been studied as a new biomarker,especially in acute myocardial infarction(AMI)and heart failure.Although there is no definitive evidence that micro RNA can surpass traditional biomarkers,such as cardiac troponin,in the diagnosis of AMI,micro RNA has the potential to complement existing risk prediction models and serve as a valuable marker for post-ami prognosis.Currently,the research methods on micro RNA have been relatively mature.In recent years,the research on micro RNA mainly focuses on the function and mechanism of micro RNA and the correlation between micro RNA and diseases.High throughput sequencing can discover unknown micrornas.So far,about 700 micrornas in human beings have been cloned and verified by sequencing,and the estimated number of micro RNA genes in the human genome is as high as 1000.Recently,a large number of studies at home and abroad have found that intracellular micro RNA can enter the body's peripheral circulation through active secretion or passive release,and cells can resist the degradation of RNA enzymes,so they can be stably stored in extracellular fluid,including various body fluids,serum and plasma Clinical blood samples are easier to obtain than tissue samples,and the relative stability of serum or plasma micro RNA makes it an ideal and non-invasive biomarker for tumors and other diseases.At present,many domestic and foreign scholars have carried out many studies on the use of circulating micro RNA for the diagnosis of tumor-related diseases,cardiovascular diseases,and hepatobiliary diseases,etc.,confirming the possibility of using different circulating micro RNA in the body as biomarkers for different diseases.ObjectiveRat offspring of moving plateau main viscera observation,the situation of the development of plateau offspring of rats to heart tissue morphological change,further study on plateau hypoxia relationship with CHD,in order to provide scientific theory basis for oxygen deficiency disease prevention and control.Combining with a case of a Tibetan normal neonatal compared with two cases of Tibetan children with CHD,and serum mirnas expression profile analysis,find out and the normal control group difference expression of micrornas,preliminary discussion as to identify the value and clinical significance of molecular markers of congenital heart disease,evaluating the prospects of mirnas for congenital heart disease screening,and to further elucidate the pathogenesis of congenital heart disease to provide reliable experimental basis.For the development and development of the plateau region to provide good birth and good nursing and painless,effective and advanced diagnosis and treatment means.Methods1.Wistar rats aged 8 weeks(18 females and 6 males)were divided into plateau group and plain group on average.12 rats(9 females and 3 males)in each group were conceived in cage at a ratio of 3:1,and all the pregnant rats gave birth naturally.Compare plateau and plain group offspring rats after the birth of the first day,30 th days,60 th days weight and heart,liver,spleen,lung,kidney,brain,viscera index,HE staining detection for the heart tissue pathology change. 2.Serum of CHD children and normal control group was collected,and each sample was 2ml,which was sent to Beijing Zhongkangbo Biotechnology Company for human miRNA detection using THE micro RNA chip of ONFEI,to find micro RNA with different expression between the two groups.Results1.The pregnant mice in each group had normal diet and no premature birth and death.2.The birth rate of offspring rats in the plateau group and the plain group was basically the same.The average number of offspring rats per litter was 11-15 and 12-17,and the total number of offspring was 109 and 122,respectively.3.The body weight of the offspring rats in the plateau group on the first day of birth was lower than that in the plain group,which was 6.20±0.77 g and 6.60±0.90 g,respectively(p<0.05).There was no difference in body weight between the two groups on the 30 th and 60 th days.4.The weight gain of the offspring rats in the plateau group and the plain group was 3.87g·d-1,4.18g·d-1(p>0.05).5.Some offspring rats in the plateau group and the plain group showed low activity and anorexia? 6.There was no significant difference in the viscera index of liver,spleen,lung,kidney and brain between the two groups on day 1,day 30 and day 60(p >0.05).Except for day 1 and day 30,the heart index of day 60 in the plateau group was 0.76±0.11,and that in the plain group was 0.61±0.01,which was significantly higher in the plateau group than in the plain group(p<0.05).7.HE staining of the myocardial tissue of the children of the plateau group showed that the myocardial interstitium was infiltrated by inflammatory cells,the structure of the myocardial cells was destroyed,the nuclei disappeared,the cytoplasm was dissolved,and the homogenized red staining was observed.Part of the myocardial fibers showed irregular fractures,cavitation of different sizes,enlargement of the myocardial space,and hyaline changes of the arterioles.8.Compared with the normal group,the up-regulated gene were: 21,the down-regulated gene were: 24.Conclusion1.The weight of the offspring rats in the plateau group on the first day of birth was lower than that in the plain group,suggesting that the hypoxia environment in the plateau may affect the growth and development of the fetus.2.There was no significant difference in the viscera index of liver,spleen,lung,kidney and brain between the two groups on day 1,day 30 and day 60(p >0.05).Except for day 1 and day 30,the heart index of the offspring rats in the plateau group was higher than that in the plain group on day 60 after birth(p<0.05).The cardiac index increased at day 60,indicating that there might be pathological changes of hypoxia in the heart of the offspring rats.This is because after the pregnant rats migrated to the plateau,the cardiac function of the offspring rats showed abnormalities in the growth process due to the long-term stimulation of hypoxia factors and the compensatory increase of the heart.3.There were infiltration of inflammatory cells in the myocardial interstitium of the children of the plateau group,the structure of the myocardial cells was damaged,the nuclei disappeared,the cytoplasm was dissolved,and the homogenized red staining was observed.Some myocardial fibers were irregularly fractured,the myocardial space was enlarged,and the small arteries were hyaline.It suggests that there is indeed hypoxia change in the heart of the offspring rats,which may be related to the heart injury of the offspring rats after birth caused by hypoxia stimulation after the pregnant rats migrated to the plateau.4.The expression of serum miRNAs was different between the CHD group and the normal group. |
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