| Atrial fibrillation (AF) is one of the commonest clinical arrhythmia. According to epidemic disease survey, AF's morbidity has been an increasing trend for the past few years, the older people are, the higher the morbidity is; people of organic cardiopathy even have a morbidity up to 40%. Not only would AF seriously influence life quality in paroxysmal clinical symptoms, but also the comparative high incidence of its thromboembolism would cause obvious increase of cripple and death. Thus, it has been a focus of people to pay attention to probing into its pathogenesis and preventive treatment.Recently, great progress has been made on AF mechanism, It is considered that the origin and maintenance of AF is the result of a variety of mechanisms to participate, despite the interaction of multiple factors in the pathogenesis of AF makes it extremely complicated, but which mainly refers to 2 aspects:The first is triggering factors, which is reflected in stimulus between sympathetic nerve and vagus nerve, leading to tractive function of bradycardia, atrial premature contraction, atrial tachycardia and ventricular block towards atrium cordis, change pressure of atrium cordis, then AF occurs; the second is structure reconstitution and electricity reconstitution, which are good for forming fold-back. AF electricity reconstitution mainly includes time limit shortening of ERP and AP of atrium cordis, AP's conduction speed decreases, ERP's divergence factor increases change of isoelectric physiological feature, which are good for occurrence and maintenance of AF, foundation of electricity reconstitution is change of cardiac atrium myocytes ion channel and transmembrane ion flow. Reconstitution of atrium cordis structure is mainly reflected in 2 aspects:The first is change of cardiac atrium myocytes ultrastructure, including regressed nature change of cardiac atrium myocytes, mitochondria swell, iliac crest disappearance, unspecialized region broadening of intercalated disc, glycogenosome decrease and myofibril increase; the second is change of cardiac atrium mesenchyme, which is shown in hyperplasia of cardiac atrium interstitialfibers, atrium cordis accretion, inconsistent electricity conduction by mesenchyme fibrosis, these are good for partial conduction retardant or fold-back and causes occurrence of AF. While changes on molecular level is shown in degradation of structural proteins and contractile proteins, disorganized gap junction proteins and degradation of ion channel proteins, which lead to abnormality of cardiac atrium myocytes junction and signal conduction and cause occurrence and maintenance of AF.It has been found in the field that OFR, genovariation, autonomic nerves dysfunction, ion channel abnormal and inflammation reaction have all relationship with occurrence and maintenance of AF, while relation between inflammation and AF has been increasingly valued by people. Obviously increase changes of CRP and IL-6 when AF occurred were reported by Bruins etc in 1997 for the first time, soon afterwards scholars further proved that AF's occurrence and development had relation with not only CRP but also other inflammatory factors as IL-8, TNF-αetc; on one hand, all the experimental results have established position of inflammation in AF, on the other hand, they have indicated that inflammation is a potential independent factor and reason for occurrence of AF.IL-10 is a kind of albumen found in Th2 cell supernatants fluid of little mouse by Fiorentio in 1989, which can restrict function of Th1 and is called composition and inhibiting factor of cell factor as a result. IL-10 can restrict activated T lymphocyte,natural killer cell and macrophage from generating cell factor, and expression of main compatible organ antigen II molecule on surface of mononuclear phagocyte and reduce antigens submission capacity of antigen presenting cell, besides, it has been found that IL-10 can restrict ventriculus sinister collagen deposit after myocardial infarction of big rat and improve reconstitution of heart ventricle, thus, it plays important role in regulating inflammation reaction and restrain heart reconstitution. For the past few years, a kind of new inflammation marker-PTX3 has been found, whose level has been proved obviously rising in coronary heart disease, acute coronary syndrome and has relation with danger layering of unstable angina pectoris. Relativity to acute coronary syndrome, plasma PTX3 level exceed CRP. However, PTX3's function in AF's occurrence and development and its relation with IL-10 have been rarely known at present, thus, IL-10 and PTX3 of cardiac atrium myocytes for AF patients are studied in the thesis, aiming to reveal their functions in AF and offer experimental basis for inflammation and AF theory.Purpose:To discuss function and mechanism of PTX3 and IL-10 in AF's occurrence and maintenance and to offer experimental grounds for further prompting relation between inflammation and AF, prevent occurrence of AF and cure it positively.Method:1 Research object:According to Declaration of Helsinki,22 patients suffering cardiac surgical operation are selected after gaining preoperational discussion of Ethics Committee and permission of patients and family members,11 in AF group,6 men and 5 women with age of 41.5±4.3 years,9 patients haveⅡdegree heart function,2 patients haveⅢdegree heart function, no additional arrhythmia medical history,AF time is over 1 year.11 in SR group,5 men and 6 women with age of 40.7±5.3 years.8 patients haveⅡdegree heart function,3 patients haveⅢdegree heart function, no arrhythmia medical history. Age, gender, heart function NYHA grade, electrocardiogram, ultrasonic cardiogram and related laboratory examination are all recorded in the two groups. Hyperthyroidism, dilated cardiomyopathy, chronic pulmonary heart disease, acute infection, fat, rheumatic disease, blood and hemopoietic system disease, internal secretion and metabolic disease, serious liver dysfunction, recent application of antibiotics, aspirin (exclusive of disuse 7 days before operation), ACEI and ARB, statins adjustment lipid deugs are all not listed in this research scope.2 Sample collection:Extracorporeal circulation should be established in the cardiac surgery and 500mg auricula dextra before cardiac arrest should be acquired, removing blood and adipose tissue, among which 200mg is imbedded with liquid nitrogen, input and frozen in -70℃profound hypothermia refrigerator for reservation. observe changes of cardiac atrium myocytes IL-10 and PTX3 of chronic AF patients by PCR method and WB method. On top of 300mg,Put 10ml oxygen-saturation non-calcium liquor under 37℃preservation and send it to the laboratory within 5-10 minutes. In separation of cardiac atrium myocytes, firstly, becomes the AF component 8, in 4, some 3 join separately concertration on 8μg/ml, 10μg/ml.12μg/ml PTX3 each lml, with in addition 1 and the SR group together puts in the thermostat,affects 1h, observes the KAch gene and protein change by PCR method and WB method; After another 4 make the patch,3 join the different concertration PTX3 each 1ml in the perfusate, affects 20min, determines the IKAch density by the patch clamp technique. Moreover, becomes the AF component 2,1 joins the lml concertration 12μg/ml PTX3, with addition 1 and the SR group puts in the thermostat together, affects 1h, the collection supernate, by PCR method,WB method and the ELISA method observes IL-6,TNF-αlevel and NF-κB gene and protein change. Finally, becomes the AF component 4, after making the patch,1 joins the 1ml concertration 12μg/ml PTX3 and 1ml concertration 10μg/ml IL-10, another two join separately 12μg/ml PTX3 and 10μg/ml IL-10 each 1ml, observes the IKAch density by the patch clamp technique.Results:1 IL-10 mRNA and IL-10 protein expression of cardiac atrium myocytes of chronic AF patients are obviously lower than SR group, while PTX3mRNA and PTX3 expression are obviously higher than SR group, Both expression of IL-10 and PTX3 take on negative correlation. significant differences in statistics exist in both groups.2,expression of Kir3.4mRNA and GIRK4 and IKAch density in AF group are obviously lower than SR group, the more increase PTX3 dose it is,the lower there are, significant differences in statistics also exist in all groups.3, NF-κBP65 mRNA and protein expression of AF group and Supernate IL-6 and TNF-αlevel of AF cardiac atrium myocytes are obviously higher than SR group, those of the large dose group are obviously higher than AF group, NF-κBP65 takes on positive correlation with IL-6 and TNF-α,significant differences in statistics also exist in all groups.4, IKAch density of large dose group +IL-10 is obviously higher than the large dose group, AF group +IL-10 is higher than AF group and large dose group + IL-10, significant differences in statistics also exist in all groups.Conclusions:1 IL-10 and PTX3 participates in occurrence and maintenance of AF.2 PTX3 can make AF occurrence and maintain,by means of influencing on current density of KAch, expression of Kir3.4mRNA and GIRK4 protein.3 PTX3 can promotes inflammation reaction and cause restructure of atrium cordis, by means of influencing on NF-κB, IL-6 and TNF-αof cardiac atrium myocytes of chronic AF patients.4 IL-10 can restrict AF inflammation reaction to some extent, and restrict in restructuring AF atrium cordis.
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