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Experimental Study Of Therapy Of Shenmai Injection On Viral Myocarditis Mice And Impact Of A Hot And Humid Environment On Therapeutic Effect

Posted on:2010-09-26Degree:MasterType:Thesis
Country:ChinaCandidate:F GuoFull Text:PDF
GTID:2144360272997403Subject:Nursing
Abstract/Summary:PDF Full Text Request
Viral myocarditis (VMC) is a common cardiovascular system diseases of pediatrics, is a main pathogeny of acquired heart disease in children. The myocardial injury which was caused by viral toxin is diffuse or limited. with the development of the state of the illness, viral myocarditis can be divided into two types, acute viral myocarditis and chronic viral myocarditis. And its clinical manifestations depend on the degrees and sites of myocardial injury. The most viral myocarditis patients can be cured, but the recurrence rate is high, up to 10% - 25%. The light type of viral myocarditis is almost asymptomatic, but the severe type is fulminant myocarditis, can cause acute heart failure or severe arrhythmias, even sudden death. Many virus can cause viral myocarditis, the most common virus is Coxsackievirus B group (CVB). Viral myocarditis which was cause by virus infection, is inflammatory lesions of myocardium, and the lesions are diffuse or limited. The infiltration of inflammatory cells is one of characteristic pathology changes of viral myocarditis. After the myocardial cells were infected by Coxsackievirus B3(CVB3), the myocardium was infiltrated by a lot of mononuclear cells, natural killer cells (NK cells) and cytotoxic T lymphocyte (CTL), and, the focal necrosis and the fibrosis appear.At present, we consider that the direct effect of virus and immune dysfunction are primary viral pathogenesis of myocarditis. Enterovirus infections and abnormal expression of cytokines have a close relationship with myocardial injury in human. First, it is possible that enterovirus directly damages the myocardial cells through its protein kinase. Second, myocardial cells which have been damaged can cause the body's autoimmune response, it mean that the inflammatory cells attack the normally myocardial cells, which cause the death of myocardial cells and pathology changes of myocardium, at the same time, after the virus infect the heart, it induce the appearance of a large number of inflammatory cytokine. Oxygen free radicals (OFR) are toxic intermediates which were produced in myocardial metabolic process. In normal state, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of myocardial cells can eliminate effectively the Oxygen free radicals, and this process can keep the balance of the generation and elimination of reactive oxygen species, and also can avoid injuring the myocardial cells, which was done by reactive oxygen species, and keep normal physiological function. When the virus have invaded the myocardial cells, the cytokines can induce the mitochondria of the myocardial cells change their structure and function, and make the mitochondria release reactive oxygen species, generate more endogenous oxidants. The increase of reactive oxygen free radical in cells can cause the rupture of nucleic acid, the depolymerization of polyhexose, the overoxidation of unsaturated fatty acid, and also can injure the myocardium through injuring the myocardial cells and changing oxidative phosphorylation of mitochondria. tumor necrosis factor-α(TNF-α) is a kind of cytokine, which have a lot of biological effects, and was excreted by T assistant lymphocyte (Thl cell), at the same time, TNF-αhas a wide range of biological activity, for example, regulating immune response, promoting the growth and differentiation of the cells, participating the body's immune response. TNF-αhas a close relationship with many illnesses, has the function of anticarcinoma, antivirus, anti-infection, and repairing the injured tissues, participates a series of pathophysiological processes, the metabolism of protein and fat of the normal cells, apoptosis, and so on. TNF-αis a very important inflammatory response medium and immunoregulatory factor.The key of the treatment of viral myocarditis is to eliminate the infectious virus in the myocardial cells and restrain immune response, but now, there are not effective drugs for treatment. Shen Mai injection consists of Hong Shen and Mai Dong, so Shen Mai injection not only has the function of anti-heart failure, but also has the function of improving the metabolism of myocardium tissues, increasing the blood stream of myocardial cells, enhancing the capability of tolerating hypoxia, decreasing the oxygen consumption of myocardial cells, protecting and repairing myocardial cells and the function of anti-arrhythmia. The hot and humid environment can make the body feel discomfortable, if this environment continues a long time, the body will have a state of high- consumption, high metabolism and easy infection, then, the disorder of circulatory system and endocrine system and the heat injury of brain tissue cells will appear.This research successfully establishes the model of viral myocarditis, after choosing CVB3 as pathogeny to infect the mice. Through measuring the content of TNF-αof myocardium, the integral of myocardium pathology, the value of cTnI,LDH,CK,CKMB in blood serum, we want to discuss the therapeutic effect of Shen Mai injection for viral myocarditis and the effect of The hot and humid environment for viral myocarditis mice.The expression find that the mice which have been inoculated CVB3 three days have a series of abnormal reaction, for example, slow moving, erecting hair, losing appetite, rejecting feeding, biting with each other, losing weight, lacking reaction for stimulation, or irritability. The fourth day, the symptoms are worse, even the death happen, the necrosis of myocardial cells and soakage of lymphocyte and monocyte of myocardium were found under light microscope, the seventh day, mortality rate reached a peak, then we can see more necrosis focus of myocardium, even large areas of necrosis, accompanied by a large number of inflammatory cell infiltration. If the mice can Survive 14 days, the symptoms will gradually lighten, at this time, the inflammatory necrosis focus will begin to be absorbed, different degrees fibrosis will appear, the 21th day, the inflammatory cell of myocardial tissues will decrease, and connective tissue will proliferate. The mice of Shen Mai treatment group have later and lighter symptoms and higher survival rate than the virus group. Similarly, myocardial cells necrosis and inflammatory cell infiltration of myocardial tissues of Shen Mai treatment group are lighter than the virus group.The expression of TNF-αpositive can be seen in the myocardial cells and the cells infected by virus, the expression of TNF-αpositive of myocardial cells happens on the 4th day, the strongest expression comes out on the 7th day which is the peak time of inflammatory cell infiltration, the expression declines after the 14th day, the course has entered the chronic stage of disease till the 21th day, infiltrating cells substantially reducts, and the expression of TNF-αalso decreases significantly. After treated with ShenMai injection, the TNF-αexpression of mouse myocardial tissue appears on the 4th day, compared with virus group, there is no significant difference(p >0.05), so no statistical significance. The positive expression of TNF-αof myocardial tissue of ShenMai injection mice group slightly enhances, there is significant difference conpared with control group and virus group, so there is statistical significance. The positive expression reduces on the 14th day, lower expression happens on the 21 th day, there is significant difference among the three groups, there is statistical significance. With the gray value of the positive expression of TNF-αdecreases, myocarditis symptoms of mice gets worse, and the positive expression of TNF-αis at the minimum gray value, pathological myocardial injury is also markedly, so there is a negative correlation between the positive expression level of TNF-αand the points of cardiomyopathy.In this study dynamic changes happen on cTnI after the mice infected CVB3, the concentration reaches peak on the 4th day, and decreases after the 7th day, then reaches minimum on the 21th day. In ShenMai injection treated group, the level of CTnI of mice also shows the dynamic changes, the concentration reaches peak on the 7th day, and lower than the virus control group. the level of serum CKMB of mice infected with CVB in virus and ShenMai injection group both reached the highest level on the 4th day, However, the level of serum CKMB in virus group was significantly higher than in ShenMai injection group(p<0.05). and then the level of serum CKMB of mice in this rwo groups gradually decreases, untill the 7th day to maintain a high level, then gradually declines, almost close to normal levels. From the curve of serum CKMB in this rwo groups view, both ShenMai injection and virus group reflect a peak on the 4th day, and the pesk maitains about a week, then gradually reduces, and the serum CKMB of ShenMai group increases less than the virus group, which shows ShenMai can inhibit the release of CKMB from myocardial cell infected virus,and play a protective role for myocardial cells. The level of ShenMai serum CK of mice infected with CVB significantly increases on the 4th day, compared with virus group there is no significant difference(p>0.05), there is no statistical significance. The level gradually reduces, untill the 21th day to remain at a relatively low level, compared with the control group, there is no significant difference, so no statistical significance. The level of serum LDH of virus mice group appers later, and the duration in body is longer, in this experiment, the level of serum LDH of mice infected CVB begins increasing on the 4th day, reaches the peak on the7th day, and gradually declines from the 14th day, but on the 21th day there is a significant difference among the groups(F=14.175,P<0.01), so there is statistical significance. The level of serum LDH at various time in Shenmai mice group is lower than in the virus mice group, the infected serum LDH level of ShenMai mice group is close to the level of the control mice group(p>0.05).
Keywords/Search Tags:a hot and humid environment, viral myocarditis, Shen Mai injection, tumor necrosis factor-α(TNF-α)
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