| Objective：Use dexrazoxane and creatine phosphate sodium on rats after irradiation,observe the protective effect and discuss its possible mechanism,and make preparations forthe further studies and clinical application.Methods：100healthy male Wistar rats(weight180±20g) were randomly divided into5groups randomly: the normal control group,the radiation group,dexrazoxane protectiongroup,sodium phosphocreatine protection group and dexrazoxane combined with sodiumphosphocreatine protection group. According to time of observe,10d,20d,40d and60d,eachgroup were randomly divided into4subgroups.Irradiation group and protective group ratswere given an intraperitoneal injection of7%chloral hydrate anesthesia (0.5ml/100g), andthen irradiated in precordium by X-ray which does was20Gy, dose rate:2Gy/min, distance:lm. Each rat of dexrazoxane protection group was given an intraperitoneal injection ofdexrazoxane(125mg/kg)30minutes after irradiation and an intraperitoneal injection ofdexrazoxane(50mg/kg) once a week after irradiation till the end of the experiment; creatinephosphate sodium in rats after irradiation with phosphate creatine sodium200mg/Kg, once aday, for3days; dexrazoxane combined with sodium phosphocreatine protection groups ofrats30minutes after irradiation given dexrazoxane (10mg/ml)1.25ml/100g intraperitonealinjection and creatine phosphate sodium,,200mg/Kg, once a day, for3days, give therdexrazoxane(10mg/ml)0.5ml/100g by intraperitoneal injection, once a week, until the end ofthe experiment. The normal control group and simple radiotherapy group at the same time theintraperitoneal inject the same volume of saline. After irradiation,10d,20d,40d,60drespectively for each subgroup of rats, abdominal aortic blood3-5ml, centrifuged upperserum, serum lactate dehydrogenase (LDH), N-terminal brain natriuretic peptide(NT-proBNP), super oxide superoxide dismutase (SOD) and malondialdehyde (MDA)content, heart removed after taking blood, and each heart of rats in corresponding subsets wasextirpatived, the left ventricular wall were taken and were made into pathological section andelectron microscopic section,then its were observed. Results：1.Light microscope: under the microscope, it showed that myocardial tissue of theradiation group inflammatory infiltration, engorgement and congestion,etc, The histologicalchanges tend to get worse progressively in10d,20d,40d,60d,and bleeding occurs after60dirradiation. While, the creatine phosphate sodium, dexrazoxane and dexrazoxane combinedwith sodium phosphocreatine protection group had the similar histological changes,but therewere no bleeding, and the corresponding time of each sub group than in the simple irradiationgroup pathological changes were slight, dexrazoxane combined with sodium phosphocreatinelesion group was the lightest, followed by dexrazoxane protection group, and the creatinephosphate sodium protection group lesions as protective group most.2.Transmission electron microscope: radiation group after irradiation with10d,20d,40d,60d, with10days after myocardial nuclear swell was the most serious changes, then graduallyreduced, and mitochondrial cristae and membrane fusion, matrix and mitochondrialvacuolation, muscle fiber dissolution changes with time gradually aggravated lesions; at thesame time, dexrazoxane, creatine phosphate sodium dexrazoxane combined with sodiumphosphocreatine protection group also has the similar lesions, but the corresponding subgroup than in simple radiotherapy group and the three group the severity of light, protectivegroup compare, dexrazoxane combined with sodium phosphocreatine lesion group was thelightest, creatine phosphate sodium protective lesion group was most.3.Serum index3.1LDH in serum: the simple irradiation group of LDH in serum value increasedgradually with time increasing(p＜0.05), while the three protective groups decreasedgradually(p＜0.05), and the corresponding time of each sub group were significantly higherthan those in the normal group (p＜0.05); Creatine phosphate sodium, dexrazoxane anddexrazoxane combined creatine phosphate sodium protective group at the corresponding timeof each sub group compared with the radiation alone group at the corresponding time of eachsub group of LDH in serum were lower (p＜0.05), dexrazoxane protection group at thecorresponding time of each sub group than the creatine phosphate sodium protective group of LDH in serum were lower (p＜0.05).3.2NT-proBNP in serum: in the simple irradiation group and three groups of protectiongroup, NT-proBNP in serum increased gradually after irradiation, irradiated after20days ofirradiating were the highest, then decreased, and the corresponding time of each sub groupwere significantly higher than those in the normal group (p＜0.05); creatine phosphatesodium, dexrazoxane and dexrazoxane combined sodium phosphocreatine protection group atthe corresponding time sub compared with irradiation group at the corresponding time ofeach sub group of NT-proBNP in serum were lower (p＜0.05), dexrazoxane combined withsodium phosphocreatine and creatine phosphate sodium protection group protection group,dexrazoxane protection group comparison of NT-proBNP in serum were lower(p＜0.05),dexrazoxane protection group at the corresponding time each sub group than the creatinephosphate sodium protective group of NT-proBNP in serum were lower (p＜0.05).3.3SOD in serum: irradiation group, sodium phosphocreatine protection group withtime increased SOD in serum decreased gradually (p＜0.05), while the other two groupsprotection group increased gradually (p＜0.05), and the corresponding time of each subgroup were significantly lower than that in control group (p＜0.05); creatine phosphatesodium protection group and the irradiation group with corresponding time of each sub groupno significant difference (p>0.05); dexrazoxane, dexrazoxane combined with sodiumphosphocreatine protection group at the corresponding time of each sub group compared withirradiation alone group at the corresponding time of each subgroup and serum SOD valueswere higher (p＜0.05), dexrazoxane combined with sodium phosphocreatine protection groupand dexrazoxane protection group no significant difference (p>0.05).3.4MDA in serum: irradiation group, sodium phosphocreatine protection groupincreased with time and MDA in serum values increased gradually (p<0.05), while the othertwo groups protection group decreased (p<0.05), and the corresponding time of each subgroup were significantly higher than those in the blank group (p<0.05); creatine phosphatesodium protection group and the irradiation group corresponding time of each sub group nosignificant difference(p>0.05); dexrazoxane, dexrazoxane combined with sodium phosphocreatine protection group at the corresponding time of each sub group compared withirradiation alone group at the corresponding time of each subgroup and MDA in serum valueswere lower (p<0.05), dexrazoxane combined with sodium phosphocreatine protection groupand dexrazoxane protection group no significant difference (p>0.05).Conclusions：1. For the prevention of early radiation-induced heart injury in rats, dexrazoxaneis isbetter than creatine phosphate sodium, and the two drugs have synergistic effects.2. Rat heart early post irradiation can cause oxidation and antioxidant levels in vivoenhancement, creatine phosphate sodium for such change has no significant effect, whereasdexrazoxane can reduce this kind of change. |
PDF Full Text Request