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Effect Of Ca 2 + -CaM-CaMKâ…¡ Signaling Pathway Mahuangfuzixixin Tang On CaM / CaMKâ…¡ Based

Posted on:2015-02-27Degree:MasterType:Thesis
Country:ChinaCandidate:S X ZhangFull Text:PDF
GTID:2264330428471130Subject:TCM clinical basis
Abstract/Summary:PDF Full Text Request
Brady arrhythmias (slow arrhythmias, BA), refers to a sinus bradycardia, atrioventricular junctional rhythm, ventricular autonomic heart rate, sinoatrial block, atrial conduction block,and atrioventricular block,characterized as slower heart rate.One of the main reasons why cardiogenic shock or sudden cardiac death occurs is because of its slow arrhythmia. It is difficult to give a meaningful statistical data of the incidence of Bradycardia,but the World Health Organization data show that cardiac and cerebrovascular diseases have become the number-one killer in humans,and the incidence of bradycardia has risen. This trend is evident in recent years, especially in developing countries. Therefore,it’s of important social value and economic benefits to research and develop the anti-arrhythmic drugs and clarify its mechanism of action.1Objective:To observe the reaction of CaM and CamK II in the heart of BA rats and the relation with BA, and to observe the BA rat myocardial cell pathology morphological changes and these indicators under the Mahuangfuzixixin decoction and its group intervention, and to analyze whether there are differences among the change of different groups;while comparing its therapeutic effect with curative drugs atropine BA.2Methods:70SPF SD rats,35female,35male, weighing250to300grams, given0.2ml suspension according to the amount of15mg/kg daily,propranolol hydrochloride orally,construction rat heart Yang model,continuous administration for14days. In accordance with the principle of randomization, the70rats were randomly divided into seven groups of10rats,each weighing1OOg with1ml liquid gavage. Are located:normal control group (0.5%of the dose administered,such as sodium carboxymethyl cellulose suspension); model group (0.5%of the dose administered, such as sodium carboxymethyl cellulose suspension);positive drug group (gavage equal dose of0.5%sodium carboxymethyl cellulose suspension, intraperitoneal injection of atropine0.15mg/kg); Mahuangfuzixixin Decoction and its three different dose groups, respectively Mahuangfuzixixin soup group (MFX,4.8g/Kg/d), ephedra+aconite group (MF,4.0g/Kg/d), ephedra Asarum+group (MX,3.0g/Kg/d), monkshood+Asarum group (FX,3.2g/Kg/d)7groups. Wherein decoction medicine in each treatment group was added to0.5%sodium carboxymethyl cellulose as a suspending agent.Two weeks after treatment the following indicators were observed:1observe the general physiological activity of rats.2rats were sacrificed under anesthesia, take heart, making pathological and immunohistochemical sections, morphological observation.3the expression of CaM and CamK II in rat heart tissue BA was observed with immunohistochemical method.4reverse transcription-polymerase chain reaction (RT-PCR) was used to observe the expression of CaM, CamK II mRNA in rat heart tissue BA.3Results:3.1P lol been induced rat model BALol rats were induced by BA Cape is a relatively simple,reliable, preparation of molded high rate of animal models, BA began to die the first two weeks of rat body weight loss seen crouching Arch,apathetic,Maofa Ling chaos, such as qi activity and eating less.Heart Rate Observation1month after the normal group,model group,positive control group, Mahuangfuzixixin group and its separate each group P<0.01, the difference was statistically significant.Asarum soup group taking the drug ephedra aconite observed in heart rate,blood pressure,ECG parameters were significantly better than the positive control group. Cape chronic arrhythmias were induced in rats lol build a successful modeling.3.2Organizational Structure of P lol Mahuangfuzixixin soup are induced.Mahuangfuzixixin soup can delay or reduce the pathological changes in rats with chronic arrhythmia in some degree.3.3Mahuangfuzixixin soup for the induction of P lol CaM were affected bradyarrhythmias rat heart tissue,CamK Ⅱprotein expression.Cam model group expression and CamK II reduced in varying degrees, respectively,64.7%and51.9%in the control group compared with the control group the difference was significant (p<0.05). Atr using Western medicine treatment, Cam and CamK of expression were increased, respectively,84.6%he90.4%in the control group.MFX treatment using traditional Chinese medicine, Cam and CamK II expression were increased significantly,98.3%and92.1%for the control group. When using a demolition party agents,Cam and CamK II expression of MF group increased significantly,respectively,7.3%and95.7%in the control group, while the use of MX and XF, express Cam and CamK II although there are some upward trend, but the rise a lesser extent, were69.2%,73.3%, and79.2%,70.8%,compared with the control group were significantly different.3.4Mahuangfuzixixin soup lol induction of P are CaM bradyarrhythmias rat heart tissue affected, CamK Ⅱ mRNA expression.Cam mRNA expression in model group significantly decreased40.5%in the control group compared with the control group the difference was significant (p<0.05). Use ATR treatment, Cam mRNA expression levels rise66.3%in the control group compared with the control group, the difference was not significant. MFX treatment using traditional Chinese medicine, the amount Cam mRNA expression was significantly increased by82.6%in the control group, no significant difference (p>0.05) compared with the control group, the expression of the Cam mRNA. With the use of a different composition of the demolition party MF, MX and XF after treatment found that the three groups were demolished to make way Pharmacy Cam mRNA expression increased, but MF demolition party groups have increased most significantly,91.8%for the control group compared with the control group not significant (p>0.05) than differences. The MX and XF demolition party group rose less, respectively,65.3%and61.8%of controls, compared with the control group, the difference was significant (p<0.05). The CamK mRNA expression in the model group and the control group was also significantly decreased compared to45.0%in the control group, the difference between the two was significantly (p<0.05). After treatment using the ATR,CamK Ⅱ mRNA expression was significantly increased for117.0%of the control group. MFX decoction after treatment using the compound, CamK II mRNA expression increased89.7%in the control group. When the demolition party group after treatment,each group CamK II mRNA expression were increased, but the group rose MF mouth for114.0%of the control group, while the group rose less MX and XF,51.8%and52%of the control group, compared with the control group, the difference was significant (p<0.05).4ConclusionMahuangfuzixixin soup with some increase in cardiac function and myocardial conduction have good protection.Between-group comparison, cardiomyocytes Mahuangfuzixixin soup rats almost no variability phenomenon and the phenomenon of congestion and bleeding, pathology were observed close to the normal group, and atropine myocardial histological granular degeneration,cell nucleus around cytoplasmic dissolution phenomenon still exists, and although the group did not reach the other side demolition normal levels,but the microscopic comparison of myocardial cells,the changes in the organizational structure of the group is better than MF MX group and FX group organizational structure.Cam CamK Ⅱ the nucleus and perinuclear cardiomyocytes and expressed strong positive weakly expressed in the cytoplasm. In addition,Cam expressed in the muscle fibers also appeared in a regional phenomenon of expression, but there is no certain rules.After the Ca2+-CaM-CamK Ⅱ,allows transcription factor CCAATE/enhancer-binding protein (C/EBP) phosphorylation to regulate certain protein synthesis, if CaMK Ⅱ-δ B nucleus excessive activation can lead to cardiac hypertrophy,in animal models of cardiac hypertrophy cardiomyopathy observed increase in CamK Ⅱ expression. Use of compound decoction MFX treatment, expression CamK mRNA increased significantly compared with Western medicine atropine, when demolition party group after treatment, each group CamK mRNA expression were increased, but MF group rose the most.
Keywords/Search Tags:Mahuangfuzixixin soup, chronic arrhythmia, signalingpathways influencing CaM, CamK â…¡, Ca2+-CaM-CamK â…¡, yang typeMahuangfuzixixin soup study of chronic diseases and related mechanisms ofcardiac arrhythmias
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