| Atrial fibrillation (AF) is one of the most common arrhythmia whose incidence increases with ages. AF causes serious complications such as cerebral embolism , heart failure and so on,all of which threat the health of human beings seriously.About the Pathogenesis of AF, the theory that exciting wave conductions in atrium can lead to uneven exciting wave and split into many reentrant impulses (also called wavelet) is widely used nowadays. The permanent exisistence of depends on the quantities of the wavelets, the size of the atrial tissue,the velocity of exciting conductions and the refractory periods of the tissue. It has been found that the cause and maintance of correlates closely with atrial remodeling which may be one of the basic reasons for AF .The remodeling of atrial structure is a kind of changes of tissue structure which is displayed by myocardial apoptosis, necrosis, atrial expansion and atrial fibrosis. Atrial fibrosis is the main point of atrial structural remodeling in patients with AF which is now considered to be the basic structure of AF .Atrial fibrosis interferes the conductions of local exciting or impulsive of the atrium and cause discontinuous conductions as well as discrete distributions spatially,all of which lead to intra-atrial heterogeneity , the formation of reentry more easily and the occurrence and maintenance of AF. Though the mechanism of atrial fibrosis is still indefinite,some studis have found that many factors such as angiotensin II (Ang II), transforming growth factorβ(TGF-β), endothelin (ET), basic fibroblast growth factor (bFGF), connective tissue growth factor (CTGF), MMPs, apoptotic factors and so on have involved in the occurrence and process of atrial fibrosis. Calpain also called calcium-dependent cysteine proteolytic enzyme is widely existed in mammalian cells and correlates with apoptosis. Calpain and caspase which are two essential cysteine protease families regulate apoptosis. AF is often accompanied with calcium overload in myocardial cells which leads to endoplasmic reticulum stress (ER stress, ERS). caspase-12 is a sub-family member of the caspase . In ERS, the intracellular concentration of calcium increased and the calpain is activated which cause the activation of caspase-12 and cause cell apoptosis consequently. BNP has many effects,such as natriuretic, diuretic, expansion of blood vessels, inhibiting renin and aldosterone secretion and so on. It has been reported that chronic atrial fibrillation patients possess high BNP levels in plasma.The reason may be related to atrial pressure and volume overload. Researches have been studied about the relations of calpains, BNP and AF at home and abroad in recent years.Whether calpain increased in atrial tissues and has some effects on atrial fibrosis during AF, Whether caspase-12 increased in atrial tissue during and correlates with calpain, when BNP expresses in atrial tissue during AF and put effect on atrial fibrosis are still unknown. In this study, we compare the expressions of calpain I, calpain II, caspase12,BNP in atrial tissues of different teams,including Patients with permanent,persistent or temporal AF.All the patients have got Rheumatic Heart Diseases, the sinus rhythm team is control group.The study of the purpose is to approach the expressions of the factors above in atrial fibrosis and their effects on the development of atrial fibrillation.through the study ,we could get a new therapeutic target to prevent atrial fibrosis and atrial structural remodeling of patients with chronic atrial fibrillation.Objective: To detect the expression of calpain I, calpain II, caspase-12,BNP in atrial tissues of Patients with Atrial Fibrillation during Rheumatic Heart Disease, for the purpose of approaching the role of which in the development of atrial fibrosis and its effect on the development of atrial fibrillation,through the way ,we could get a new therapeutic target to prevent atrial fibrosis and atrial structural remodeling of patients with chronic atrial fibrillation.Methods: The left atrial tissue samples were taken from 32 patients with rheumatic heart disease who underwent heart valve replacement surgery. which is divided in A group :permanent atrial fibrillation group 16 cases, B group : paroxysmal or persistent atrial fibrillation group 10 cases, C group: sinus rhythm group (Sinus rhythm; SR Group) 6 cases. The expression of Calpain I, Calpain II, caspase12, BNP in the left atrial tissue measured by immunohistochemical method and to calculate the gray value, VG staining were used for quantitative analysis of collagen accumulation and assessed the extent of atrial fibrosis.Results:1, To compare the general data of the research:Atrial fibrillation duration at A groups (42.75±22.65 months) were much longer than B group (13.10±10.88 months) ,p <0.05, left atrial diameter at A groups (55.58±8.80mm)and B group (46.60±5.85mm) were increased significantly than C group (35.03±4.65mm), p all <0.001. Compared with B group, left atrial diameter of A Group increased significantly, p <0.01; LVEF at A group (50.91±5.85%) was significantly lower than B group (59.10±3.78%, p <0.001) and C group (62.50±6.41%, p <0.001), and then the latter two was no significant difference in LVEF. Between the three groups of patients with other clinical information such as gender, age and so no significant difference.2, To compare the gray value about calpain I and calpain II in each group:Gray value of calpain I and calpain II in C,B and A Group show increasing trend, gray values of calpain I were: C group (45.16±15.03), B group (82.38±13.79), A group (123.16±14.50 ), Comparison among the three groups, respectively, there was significant difference, p <0.001, . Gray value of calpain II were: C group (47.96±8.11), and B group (76.93±17.04), A group (117.52±21.97) have statistically significant difference (P <0.001, P <0.05).3, To compare the gray value about caspase-12 in each group :Gray value of caspase-12 in A group(70.69±11.40) and B group(62.77±14.62) were significantly higher than C group (32.86±5.72) (p all <0.001), while comparing the first two there was no significant difference.4, To compare the gray value about BNP in each group:Gray value of BNP in A group (86.24±6.50) was significantly higher than B group (63.04±5.49) and C group (40.37±3.28) (p all <0.001), Gray value of BNP in B group was also significantly higher than C group (p <0.001).5, To compare CVF in each group:CVF in A group (18.69±2.51%) was significantly higher than B group (11.95±1.73%) and C group (5.95±1.28%) (p all <0.001), CVF in PAF group was also significantly higher than C group, p <0.001).6, The relative linear analysis in each group:calpain I and calpain II in left atrial tissue and the left atrium diameter showed a positive correlation (correlation coefficients were r = 0.77, p <0.001, r = 0.72, p <0.001); calpain I, calpain II in left atrial tissue showed a positive correlation with caspase12 (correlation coefficients were r = 0.87, p <0.001, r = 0.88, p <0.001); calpain I, calpain II in left atrial tissue and the CVF showed positively correlated (correlation coefficient separately for r = 0.85, p <0.001, r = 0.81, p <0.001); collagen volume fraction of left atrial tissue and BNP showed positively correlated (correlation coefficient r = 0.94, p <0.001).Conclusion: 1,Expression of calpain I, calpain II, caspase-12 and BNP in the left atrial tissue of Patients with rheumatic heart disease(RHD) complicating chronic atrial fibrillation was significantly increased, calpain I, calpain II and CVF was a positive correlation, they participate in the process of fibrosis in RHD complicating chronic atrial fibrillation through the promotion of cardiomyocyte apoptosis. 2,Expression of BNP in the left atrial tissue of Patients with RHD complicating chronic atrial fibrillation was significantly increased, BNP and CVF was a positive correlation,BNP participate in the process of fibrosis in RHD complicating chronic atrial fibrillation. |
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