Protective Effects Of CoQ10in Rabbits With Combined Injuries Of Hypoxia And NaCN Intoxication

Plateau refers to the huge and continuous uplift area whose altitude often stands at morethan1,000meters above sea level. When the oxygen content in the air remains constant, thebarometric pressure gradually decreases as the altitude rises, resulting in the proportional fallof oxygen partial pressure, which is often called hypoxia. Hypoxia refers to the pathologicalprocess in which the tissue metabolism, function and morphological structure undergoabnormal changes caused by insufficient oxygen supply to tissues or obstacle in oxygen use intissues. It is the special environment often met in agricultural and industrial production and indaily life. Hypoxia is an important factor impacting on the health of people who hurriedlyarrive in plateaus. In China, which has many plateau terrains,38%-76%of ordinary peoplewould suffer from altitude stress when they reach plateaus whose altitude exceeds4,200meters. All people who are on plateaus or in mountainous regions for the first time wouldhave altitude stress. To a larger extent, hypoxia impacts on the functions of heart, brains,lungs and other important organs. At the same time, hypoxia environment on plateaus alsoimpacts on the toxic effect of chemical toxicants and on the therapeutic effect of antidotes.Cyanide specifically refers to the chemical compound carrying cyanide ion （CN-） orcyanogroup （-CN）. It is the highly-toxic chemical raw material. For a long time, it has alsobeen the chemical warfare agent equipped in overseas military forces. The cyanide has thefollowing characteristics: extensive sources, multiple means of contamination, and difficultyin treatment after the intoxication. After the cyanide enters the organism, it can robustlysuppress electron transfer along the cellular respiratory chain while leading to dysfunction ofoxidative phosphorylation, thus resulting in tissue hypoxia.. As a result, the disease iscomplex and the treatment is difficult.Till today, neither China nor the other countries in theworld have developed the therapeutic plan with special effect on cyanide intoxication combined with hypoxia on plateaus. As a result, the enhanced research efforts to prevent andtreat chemical intoxication have significant clinical and military meaning.CoQ10, with evident antioxidant effect, can be used to prevent or supplement thetreatment of diseases caused by heart ischemia and hypoxia. We presume CoQ10canintervene with heart dysfunction caused by cyanide intoxication or hypoxia.In light of this, the thesis, based on the previous researches, has established the animalmodel of Hydrocyanic acid, NaCN intoxication combined with hypoxia. By preventivelydosing rabbit with CoQ10for10days, we have observed the intervention effect of CoQ10onthe heart function of rabbit in cyanide intoxication and hypoxia. Besides, the thesis alsodiscusses the changes of arterial blood gas （ABG）, myocardial enzyme and oxidative stressindicators caused by CoQ10in the case of NaCN intoxication, thus providing importanttheoretical foundation for the research on prevention and treatment of NaCN intoxicationcombined with hypoxia and providing experimental and theoretical basis for makingpreventive and therapeutic protocols for cyanide intoxication on plateaus.Purpose and meaning of the experimentIn case of hypoxia abnormality, acute hypoxia and cyanide intoxication, the variousmyocardial cells would suffer from the overlapped effects caused by internal respirationsuppression and external hypoxia, thus leading to evident change in heart function. In thiscircumstance, CoQ10can play an evident anti-hypoxia role. This experiment is designed tostudy whether CoQ10can resist against toxicity caused by hypoxia and cyanide intoxication.Because the physiological structure of rabbit is similar to that of human body, it is easier tomake experimental model, the experimental result is relatively authentic and reliable, and thecost is low, the experiment plans to use the rabbit to produce the model of hypoxia andcyanide intoxication so as to study how the preventively dosing rabbit with CoQ10canintervene with the damage to its heart caused by NaCN intoxication combined with hypoxia,thus providing theoretical foundation for the research on preventive and therapeutic protocolsfor cyanide intoxication in the case of hypoxia on plateaus.Design of experimentThe Third Military Medical University, Animal Institute provides20healthy Japanesebig ear rabbits, both male and female. Each of these rabbits weighs at2.1±0.5kg. After these rabbits are placed in the lab, they can eat and drink freely in room temperature （20±3℃）, getquarantined and observed for7days before they are used in the experiment.In the experiment, the20rabbits are divided, at random, into four groups, namely, theacute hypoxia （H） group, NaCN intoxication （CN） group, hypoxia+NaCN intoxication（H+CN） group and CoQ+H+CN group. We use the normal saline or CoQ10（50mg/kg） togavage the rabbits for10days in a row. We make pentobarbital sodium injection （30mg/kg）into the abdominal cavity of the rabbits to narcotize them before making trachea and rightcarotid artery intubation. Rabbits in CN group breathe in air through the trachea cannulawhile rabbits in other groups are connected to N₂/O₂mixed gas respirators so that they canbreathe in the mixed gas for60minutes to simulate the hypoxia environment on plateaus.Rabbits in H group receive hypodermic injection of normal saline while those in other groupsreceive hypodermic injection of NaCN2mg/kg （2mg/kg）. We take blood samples in thecarotid artery at0minute before the intoxication and10minutes,20minutes,30minutes,60minutes, and90minutes respectively after the intoxication to measure arterial partialpressure of oxygen （PaO₂）, partial pressure of carbon dioxide in artery （PaCO₂）, arterial bloodPH （PH） and arterial blood bicarbonate （HCO3）. We also take blood samples in the carotidartery at0minute before the intoxication and at30minutes,60minutes, and90minutesrespectively after the intoxication to measure the contents of AST, CK, CK-MB, LDH activityand MDA in arterial blood, and compare these contents in the H+CN intoxication group（control group）.Outcomes1. The arterial blood PH value in H-group rabbits, after they breathe in N₂/O₂mixed gas,presents no significant change，The PaO₂value keeps lowering down and shows evidentchanges （P<0.05）. The PaCO₂value lowers down first before rising gradually. And the HCO3value also lowers down first before rising gradually and approaches the value in the controlgroup after90minutes.2. After breathing in N₂/O₂mixed gas, rabbits in H group have raised the activity ofAST, CK, CK-MB and LDH activity in their blood （P<0.05）. Apart from the continuous riseof CK-MB, the peak values of other indicators occur at60minutes and fall down at90minutes.3. MDA in the blood of H-group rabbits, after breathing in N₂/O₂mixed gas, rises continuously and has evident changes （P<0.05）.4. After getting intoxicated, rabbits in CN Group and H+CN group will undergochanges in their arterial blood gas contents, myocardial enzymes and MDA. Though thechanges are similar to those in H group, they are actually more evident. Rabbits inCoQ+H+CN group, after taking CoQ10in a preventive way and getting intoxicated, differsignificantly （P<0.05） from H+CN group in arterial blood gas contents, myocardial enzymesand MDA. However, there is still significant difference （P<0.05） in comparison with0minute.Conclusions1、Hypoxia and cyanide intoxication impair the significant changes of arterial blood gascontents, myocardial enzyme and blood oxidative stress indicators of rabbits.,The change isadd of both effect the index;2、The preventive dose of CoQ10obviously improved the change of the PaO₂、PaCO₂and so on arterial blood gas contents,can mitigation the impact on myocardial enzyme ofHypoxia and cyanide intoxication, Weaken the elevated of two kinds of factors as a result ofjoint action blood oxidative stress indicators MDA.