| Exemplified by the HCN, Cyanogen agents (blood agents) are highly toxic. Teir intocication effects are potent, quick and hard to defend. As a result, it has captured the attention of foreign military forces. Attachment three of the UN's ban on chemical weapons, cyanogens chloride and hydrogen cyanide ranked 2 and 3 on the list. Both of which are cynogen agents. They are referred to as"the king of speed kills". They are considered as the top chemical weapons of U.S. and Russia. After intoxication with the agent, the subject experiences hypoxia and difficulty breathing.The toxicant acts quickly and disseminates through the body with incredible speed. It could kill the subject within 10 minutes. After the cynogen agents enters the body, the CN ion stops cells from performing respiratory functions and oxidative phosphorylation. It inhibits oxidases the end of the Mitochondrial respiratory chain. This causes the tissues to die due to lack of toxic lack of oxygen. Also known as damage to"internal respiratory". Medical definition for plateau is 3 000m above sea level. Hypoxia is a characteristic of plateaus. Some people demonstrate clear symptoms of hypoxia. Any level higher than this could have substantial effects on Physiology, biochemistry and anatomy. Our country is full of plateaus. Just the Tibetan plateau alone covers 250 square kilometers of land. The plateau borders many other countries. The military values of these plateaus are of great importance. When NaCN is mixed in with the harsh environment of the plateaus, hypoxia kicks in from both external and internal. When this occurs, the rate at which a subject dies doubles. To understand and analyze the use and nature of NaCN intoxication is of great importance for national defense of our country.The heart functions under the condition of ample blood supply and oxygen. Therefore, any lack of blood supply or the level of oxygen in the blood will cause the heart to function abnormally. Sudden decrease in oxygen level could lead to fluctuation in blood pressure and heart rate. Many studies have shown that when hypoxia is induced in lab rat, the left ventricle pressure and maximum pressure decreases dramatically. Myocardial hypoxia is not only a serious post-traumatic heart failure, but also other start-induced organ damage and the formation of multiple organ dysfunction and failure of the move before an important factor. Studies have found that oxygen under the conditions of soman toxicity increased.Heart is a very sensitive organ to hypoxia; studies have shown that simple and pure hypoxia induced by NaCN poisoning can result in significant cardiomyocyte apoptosis, hypoxia leading to the main form of cell death through induction of apoptosis arising. In the use of isolated rat cardiac cells to give H / R in the way of experimental studies have found that the myocardial cells in continued lack of oxygen condition for a longer period of time have achieved reoxygenation. The animal myocardial cells in vivo ischemia / reperfusion injury is in the same situation. In hypoxia and reoxygenation, there is injury in the group. PI staining by flow of cytometry analysis of DNA histogram showed that it's lower than the number of cells in G1 phase of the increase and it was significantly higher than other groups. There are more cell apoptosis. Transmission of electron microscopy can see hypoxia / reoxygenation group of serious cardiac cell injury is a clear pre-apoptosis. Apoptosis in the late stages changes at the same time the number of cardiomyocyte apoptosis is also a noticeable increase in support for the resumption of oxygen (again Reperfusion). Injury in myocardial apoptosis is an important predisposing factor. The H / R can increase the myocardial cell damage, accompanied by an increase in myocardial apoptosis; intracellular calcium may be triggered by excessive apoptosis of myocardial factors; SOD (superoxide dismutase, SOD) can be reduced. The generation of free radicals and reduced the incidence of myocardial apoptosis and hypoxic preconditioning with anti-myocardial cells to reduce myocardial injury and apoptosis. It's likely to have lower intracellular calcium ion concentration. Fliss, and so on in the body in an animal subject study also found that the apoptosis of myocardial reperfusion injury is one of the characteristics. Reperfusion injury can accelerate irreversible apoptosis. Musat-Marcu and so on at the heart of rat in vitro perfusion can be found in its early occurrence of myocardial apoptosis, and inhibit apoptosis in the post along with the restoration of heart functions. This suggests that cardiomyocyte apoptosis isinvolved in the attenuation of cardiac function.Cytochrome C (Cyt C) and apoptosis-inducing factor are located in normal mitochondria mitochondrial membrane and space. Ischemia / reperfusion time, PT and the opening hole damage, Cyt C and AIF were released into the cytoplasm. Cyt C with the cytoplasm of apoptosis-activating factor-1(apoptosis-activating factor-1, Apaf-1), followed by activation of acid cysteine protease family of Caspase-9, Caspase-3 and start the apoptosis pathway, activation of Caspase-3 can be in the cytoplasm of the role of the cytoskeleton protein, or acting on the nuclear DNA, lead to apoptosis. The AIF was released by PT hole into the cytoplasm, the translocation into the nucleus, activated endogenous endonuclease chromosome will be cut for several times the entire 180-200bp fragment of DNA, at the same time to speed up the release of cytochrome C and further promote cell Apoptosis. Cyt C, AIF can be seen as apoptosis of the two channels in cardiac cells. They play an important role in apoptosis.Hypoxic preconditioning, and can be defined as "a short period of time in advance to repeat non-fatal ischemic / hypoxic, the body of the cell was followed by a long-fatal ischemic / hypoxic injury A high degree of tolerance."Hypoxic preconditioning on myocardial cells can generate Preconditioning. Hypoxic preconditioning so far is considered to be one of the most powerful endogenous myocardial protective measures. Ginsenosides can act as antioxidants to free radical damages to the heart, to maintain the integrity of myocardial cell membrane and improve acute myocardial ischemia diastolic function. But also against myocardial ischemia-induced myocardial necrosis is irreversible, so that the increased activity of SOD can release myocardial PCK Reduction. Ginsenosides have significant protective effects on ischemia-reperfusion injury in cell necrosis and apoptosis.In addition, taurine removes oxygen free radicals and protects the cell membrane, so that the enzyme reduces the release of liver enzymes, which are very anti-oxidized. It also can regulate the intracellular calcium homeostasis, reduces limb ischemia reperfusion. During calcium influx, neutrophil respiratory burst a large amount of H2O2 and CL, having a combination of difficulty to get rid of the strong oxidizer - hypochlorous acid and Taurine With hypochlorous acid, to form a stable low-oxidants-taurine chloramine, and thus clear the hypochlorite on the role of cell damage. Therefore taurine corrects limb ischemia-reperfusion injury in distant organs. Application of taurine in the long course of treatment to lower blood pressure and reversal of cardiac hypertrophy are highly possible. High blood pressure also reduces myocardial apoptosis, and can reduce myocardial Angâ…¡content and ACE activity. As a result, we believe that the long course of taurine treatment of high blood pressure can inhibit myocardial apoptosis and reverse cardiac hypertrophy. The role of antagonist drugs may be related to local organizations related to the generation of Angâ…¡. Taurine inhibition of myocardial apoptosis also may be related to apoptosis-related gene regulation Fas, Bax and Bcl-2 protein expressions. Taurine can protect myocardial cells and avoid the occurrence of cardiac malformation, at the same time have lower blood pressure.The normal supply of blood and oxygen to heart bring into full play. Accordingly, some adverse factor that result lower oxygen content of blood and insufficiency of blood for the cardiac muscle will lead to abnormal cardiac function.Hypoxic environment of cyanide poisoning changes how the heart functions? How the mechanism of the heart resulting in injury? What are the characteristics of myocardial apoptosis? How to search for possible interventions? Research on these issues has not been reported so far. To be the subject of the preliminary research on the basis of the establishment of hypoxia and cyanide poisoning of animal models and cell models to study hypoxia on the compound sodium cyanide poisoning Cyt C, AIF apoptosis two way interference with the role of hypoxia to find Cyanide poisoning and two different factors at the same time under myocardial apoptosis. The key to explore the hypoxic preconditioning, as well as ginsenosides is taurine and anti-hypoxia medicines interference with the effects of hypoxia environment for the prevention and treatment of cyanide poisoning research Theory. Based on this subject in both cases, the use of laboratory animals in general studies and cell culture in vitro study of the combination will implement both methods. By observing the simulation of composite NaCN high altitude hypoxia in rat poisoning on heart structure and function as well as myocardial hypoxia and NaCN poisoning After Cyt C, caspase-3 and AIF expression of quantitative analysis, as well as Cyt C and AIF caused by apoptosis analytical effect, to explore simulated hypoxic conditions of NaCN poisoning after cardiac function changes in the characteristics of myocardial apoptosis. The future of hypoxic NaCN poisoning prevention measures the medical treatment studies and it provides important theoretical basis. For the ultimate development of composites hypoxia NaCN poisoning prevention and treatment programs, it will implement the following methods.Method:1. Testing whether interventions of hypoxia and NaCN intoxication after rat cardiac structures will function. Utilizing methods include hemodynamics, ECG, myocardial enzymes, myocardial biopsy light microscope, such as electron microscopy observation;2. the establishment of in vitro NaCN poisoning induced by hypoxia and myocardial cell damage model to detect hypoxia and NaCN poisoning under the conditions of myocardial apoptosis and its interventions on the impact of cardiac apoptosis;3. any intervention under the circumstances NaCN complex cardiomyocytes hypoxia poisoning after caspase-3, Cyt C and AIF expression detection, analysis Cyt C and AIF caused by the two channels the characteristics of apoptosis;Results:Part one: Change of hypoxia and NaCN intoxication on structure and fuction in rat.1. Hemodynamics of rat in the plain experimental group takes place change after NaCN intoxication. These markers, such as HR, mLVSP, +dP/dtmax show up significance descent(P<0.01) and the amplitude of T wave show up significance elevation(P<0.01) after NaCN intoxication than no NaCN intoxication. Then, they get a recover to normal value after 30 minute.2. Hemodynamics of rat in plateau experimental group take place more evident change after NaCN intoxication than the plain experimental group. These markers, such as HR, mLVSP, +dP/dtmax show up significance descent(P<0.01) and the amplitude of T wave show up significance elevation(P<0.01) after NaCN intoxication than no NaCN intoxication. Then, they get a recover to normal value after 40 minute. Nevertheless, the recover degree and effect is bad.3. Change of the cardiac muscle enzymogram in the plateau experimental group is more obviously than in plain experimental group, and it shows up significant difference (P<0.01). This change difficultly put back. Variation of LDH value is the most significant, and it is with one accord that anaerobic respiration corresponding reinforce in the hypoxia environment. 4. The activity of Cyt C show up significant decrease after NaCN intoxication in plain experimental group. Behind tow hours, the activity occur evident recovery.5. Compare to in plain experimental group, the activity of Cyt C in plateau experimental group show up significance decrease after NaCN intoxication. Behind tow hours, the activity occur recovery to normal value, but this recovery is the more slowing.6. Cardiac muscle tissue damage of rat gradually aggravate in plain experimental group after NaCN intoxication. It is the most severity after two hour. There is lacune formation in interstitial substance, and showing up fibrilla cataplasia, transverse striation no clear, diffuse hyperemia, hydropic degeneration, and so on. There is apparent recovery after six hour.7. Cardiac muscle tissue of normal rat occur some symptom in plateau experimental group, including hyperemia, hydropic degeneration, colour shallowness, focal inflammation cell, etc. Myocardial damage rapidly aggravate after NaCN intoxication. There are severely hydropic degeneration, diffuse cellular swelling, cytoplasm ambiguity, hydrops capsule, cell degeneration and interstitial substance vasocongestion. These symptoms don't emerge recovery after six hour.8. Mitochondrion of rat occur light hydrops and swelling and distension, deliquescence, cristae and membrane fusion or delitescence in plain experimental group after NaCN intoxication two hour.9. Mitochondrion of rat occur light hydrops and swelling and distension in plateau experimental group. It shows up obviously Swelling, cristae and membrane fusion or delitescence, etc. after NaCN intoxication. Degree of injury is the more severity.10. HPC, SPG and Tau bring out comparative effect to Hemodynamics of rat after hypoxia and NaCN intoxication. These indexes, such as HR, mLVSP, +dP/dtmax and amplitude of T wave show up less change degree. Rat gets obviously recovery.11. Activity of Cyt C of HPC rat shows up significance depress after NaCN intoxication, and gets recovery after two hour. The recovery effectiveness is better in HPC rat group than in plateau rat group, and worse in HPC rat group than in plain rat group.Part two: Apoptosis detection of origin generation cardiac muscle cell of SD neonate rat1. Model constructing of cardiac muscle cell of SD neonate rat used NaCN narcotics. 2. Assay of IC50 value of origin generation cardiac muscle cell of SD neonate rat. IC50 value is 87.85mmol/L.3. Origin generation cardiac muscle cell of SD neonate rat show up apoptosis by IC50 dosage NaCN used narcotics, and Cell Nucleus appear sapphirine owing to chromatin enrich, and so on.Part three: Expression detection of Cyt C, caspase-3, AIF in cardiac muscle cell of SPG and Tau intervention rat after NaCN intoxication1. There are Expression up-regulation of Cyt C, caspase-3 and their mRNA of hypoxia and NaCN intoxication rat after 30 minute in cardiac muscle tissue endochylema.2. There is Expression up-regulation of AIF of hypoxia and NaCN intoxication rat after 30 minute in cardiac muscle tissue endochylema. But, Expression of AIF mRNA show up insensitivity to NaCN used narcotics.3. HPC, SPG and Tau interventions bring out comparative effect to Expression depress of Cyt C, caspase-3 and their mRNA, AIF after hypoxia and NaCN intoxication.Conclusion:1. Hemodynamics markers, such as HR, mLVSP, +dP/dtmax of rat in plateau experimental group show up significance descent after NaCN intoxication, and amplitude of T wave show up significance heightening. These direct that cardiac contractile function of rat occur the more severity injury.2. Biochemical indicator, such as cardiac muscle enzymogram and Cyt C activity of rat in plateau experimental group shows up significance change after NaCN intoxication. These direct that heart biochemistry metabolism of rat occur large change, and it results to cardiac function disorder.3. Ultrastructural pathology variation and injury of cardiac muscle tissue of rat in plateau experimental group get all the more severity after NaCN intoxication. Mitochondrial injury especially is possible to cause cardiac muscle cell apoptosis.4. These intervention study including HPC, SPG and Tau are effect for recover of cardiac function and Cyt C activity. They act as bolting measures for prevention and treatment of hypoxia and NaCN intoxication.5. Origin generation cardiac muscle cell of SD neonate rat show up apoptosis by IC50 dosage NaCN used narcotics. Otherwise, cardiac muscle cell apoptosis has induced by purely hypoxia. These hint cardiac muscle cell apoptosis all the more severity under hypoxia and NaCN intoxication koinonia, and it may be important reason of heart injury.6. There are Expression up-regulation of Cyt C, caspase-3 and their mRNA of hypoxia and NaCN intoxication rat after 30 minute in cardiac muscle tissue endochylema. Action of mitochondria caspase dependency way is obviously to cardiac muscle cell apoptosis, and it may bring out good effect for prevention and treatment of hypoxia and NaCN intoxication.7. SPG and Tau interventions bring out comparative effect to Expression depress of Cyt C, caspase-3 and their mRNA, AIF after hypoxia and NaCN intoxication. It hint SPG and Tau maybe act as bolting measures for prevention and treatment of hypoxia and NaCN intoxication.8. There is expression up-regulation of AIF of anoxia and NaCN intoxication rat after 30 minute in cardiac muscle tissue endochylema. But, it is not obviously to expression change of AIF mRNA. These results direct that sensitive degree of AIF mRNA expression is better in hypoxia rat than in NaCN intoxication rat, and cardiac muscle cell apoptosis mechanism of mitochondria caspase dependency way is different with mitochondria non-caspase dependency way after NaCN intoxication, and cardiac muscle cell apoptosis mechanism of hypoxia is different with NaCN intoxication. These results are worth for lucubrate.
|
PDF Full Text Request