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Effects Of PTX3 On Acetylcholine Sensitive K+ Channel (KAch) In Chronic Human Atrial Fibrillation

Posted on:2012-01-20Degree:MasterType:Thesis
Country:ChinaCandidate:M Z DuFull Text:PDF
GTID:2154330332499203Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
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.With the research of ion channal on the occurrence and maintenance of AF recently,scientists have found a series of ion channals (such as Na+ Channal,K+ channal,Ca2+ channal,CL- channal) related with the occurence of AF closely.KAch only exist in atrium myocytes,so the relation between KAch and AF has been increasingly valued by scientists. Lots of reports have indicated that some changes of KAch appeared in atrium myocytes of AF patients,and stop the changes can prevent the occurrence of AF.Therefore,the research of the relationship between KAch and AF has become a hot topic.In the past years,it has been found that 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.Recently, 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 between plasma PTX3 level and acute coronary syndrome in cardiovascular system obviously exceed that between CRP and acute coronary syndrome. However, PTX3's function in AF's occurrence and development have been rarely known at present, thus, 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 the function and mechanism of PTX3 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 have II degree 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 100mg auricula dextra before cardiac arrest should be acquired, removing blood and adipose tissue.3 Separation of cardiac atrium myocytes.4 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 1ml, 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.Results:1.Contents of Kir3.4mRNA and GIRK4and IKAch density in AF group are obviously lower than SR group, while Kir3.4mRNA and GIRK4 contents and IKAch density of the small dose group is lower than AF group, those of the middle dose group are lower than the small dose group, and those of the large dose group are lower than the middle dose group, significant differences in statistics also exist in all groups.Conclusions:1. KAch participates in the process of AF pathology.2. PTX3 reduce the density of IKAch by influencing expression of Kir3.4mRNA and GIRK4 protein. Speculated that it make chronic AF occur and maintain.3. PTX3 maybe cause restructure of atrium by promoting inflammation reaction of chronic AF patients.4. Speculated that inflammation maybe the reason of AF occurrence and maintain reasons.
Keywords/Search Tags:atrial fibrillation, acetylcholine sensitive potassium channel, Pentamer3, western blot, polymerase chain reaction
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