DFP对染铝大鼠心肌的保护作用研究
摘要
[目的]
铝是人体非必需元素,因此对铝的毒性的研究不容忽视。研究表明,铝在体内分布广泛,且在人体内蓄积并产生慢性毒性,根据暴露的途径、剂量和持续时间不同,铝在体内的“靶”器官也不同,因此其对组织及各个器官都将造成损伤。心脏是体内的泵血器官,心脏疾病引起了人们越来越多地普遍关注。因此研究铝的心脏毒性显得尤为重要。目前,重复暴露或潜在转移到其他组织的铝复合物的清除机制尚不明确,但在临床上多使用螯合剂来治疗机体金属中毒。DFP(deferiprone,1,2-二甲基-3-羟基-4-吡啶酮)以口服有效的显著特点逐渐被认识,最初被作为一种铁螯合剂,由于铝和铁的元素性质相近,本研究将DFP作为一种铝螯合剂进行动物实验,通过对心肌和血清铝的测定,心肌酶谱、心脏抗氧化系统及心、肺、血清中其他必需元素等指标的研究来评价DFP对染铝大鼠心脏毒性的保护作用。
【方法】
1实验动物处理
选用健康成年雄性Wistar大鼠,体质量160～220g,自由进水、进食。平衡一周后,按体质量随机分为5组,即阴性对照组、阳性对照组、DFP低剂量组、DFP中剂量组、DFP高剂量组。除阴性对照组外,其余各组均以灌胃方式给予氯化铝(AlCl3)染毒,阴性对照组给予相应剂量的生理盐水。每周给药5次,平衡2天后继续给药。染毒8周后,DFP低、中、高剂量组分别给予不同剂量的DFP,阴性对照组和阳性对照组给予相应剂量的生理盐水,持续2周。
2大鼠一般情况及体重的记录
每天称量大鼠体重,以确定灌胃剂量,每天观察各组大鼠的食欲、精神状态、行动、眼神及反应速度等一般状况。每周记录一次体重增长情况。
3 DFP对染铝大鼠心肌、血清铝的促排作用
取各组大鼠心肌组织及血清,用微波消解仪消化后,使用石墨炉原子吸收分光光度法测定心肌组织及血清中铝含量,观察DFP的排铝效果。
4 DFP对染铝大鼠血清心肌酶谱的影响
各组大鼠最后一次灌胃给药后,禁食禁水24h,断头取血,立即收集血液到试管中,3500rpm离心10min,吸取上层血清于E-P管中,立即依照试剂盒使用说明分别进行血清中乳酸脱氢酶、肌酸激酶、谷草转氨酶的测定。
5 DFP对染铝大鼠心肌组织抗氧化系统的影响
取各组大鼠心肌组织,加入一定量的生理盐水制备成10%组织匀浆,将制备好的组织匀浆用低温离心机3500rpm离心10min,取上清液,根据需要用生理盐水稀释后,进行脂质过氧化物丙二醛、超氧化物歧化酶、谷胱甘肽过氧化物酶的测定。
6 DFP对染铝大鼠心、肺组织及血清中必需元素的影响
取各组大鼠心、肺组织及血清用微波消解仪消化后,采用火焰原子吸收分光光度法进行组织中铜、锌、钙、铁、镁含量的测定。
7 DFP对染铝大鼠心肌组织损伤恢复的形态学观察
取各组大鼠心脏组织苏木素-伊红(HE)染色,进行病理学观察,观察铝对大鼠心肌细胞的病理形态学改变及DFP对其恢复作用。
【结果】
1大鼠一般情况及体重的记录
阴性对照组大鼠一般情况良好,进食良好,被毛浓密而有光泽,反应灵敏,动作灵活,肌肉有弹性。前4周染毒大鼠多数表现为被毛无光泽,反应迟缓,活动力较差；中、高剂量组给予DFP前两天有少数出现皮肤发红、出汗等现象,以后均未出现异常。各组大鼠体重均增长,但增长幅度未见明显差异。
2 DFP对染铝大鼠心肌、血清铝的促排作用
与阴性对照组比较,阳性对照组大鼠心肌中铝含量升高(P＜0.01),给予DFP治疗后,低、中、高剂量组与阳性对照组比较,铝含量均降低(P＜0.05,P＜0.01),且DFP中、高剂量组与阴性对照组中铝含量无差异(P＞0.05)。
阳性对照组血清铝含量较阴性对照组升高(P＜0.01),给予DFP后,DFP高剂量组血清铝含量降低(P＜0.01),但与阴性对照组相比仍较高(P＜0.01)。
3 DFP对染铝大鼠血清心肌酶谱的影响
各组大鼠血清心肌酶活力测定结果显示,阳性对照组乳酸脱氢酶、肌酸激酶的活力高于阴性对照组(P＜0.01)。在给予DFP后,高剂量组肌酸激酶活力低于阳性对照组(P＜0.01),但与阴性对照组相比未见明显差异(P＞0.05)；低、中、高剂量组乳酸脱氢酶的活力与阳性对照组相比降低(P＜0.01),但与阴性对照组比较无差别(P＞0.05)。
4 DFP对染铝大鼠心肌组织抗氧化系统的影响
各组大鼠心肌组织中丙二醛、谷胱甘肽过氧化物酶、超氧化物歧化酶的测定结果显示,与阴性对照组相比,阳性对照组心肌组织脂质过氧化产物丙二醛的含量升高(P＜0.01),谷胱甘肽过氧化物酶活力降低(P＜0.01)；给予DFP后,中、高剂量组丙二醛含量与阳性对照组相比明显降低(P＜0.05),低、中、高剂量组谷胱甘肽过氧化物酶的活力与阳性对照组相比明显升高(P＜0.01),且均与阴性对照组无差异(P＞0.05)。
5 DFP对染铝大鼠心、肺组织及血清中必需元素的影响
阳性对照组大鼠心肌铁含量较阴性对照组降低(P＜0.05),DFP低、中、高剂量组大鼠心肌中铁含量高于阳性对照组(P＜0.05),且与阴性对照组比较无差异(P＞0.05)；
阳性对照组大鼠血清铁含量低于阴性对照组(P＜0.05)；给予DFP后,低、中剂量组血清铁含量无明显变化,但DFP高剂量组血清铁含量低于阳性对照组(P＜0.05)。
各组大鼠心、肺组织及血清中铜、锌、钙、镁的含量比较差异均无统计学意义(P＞0.05)。
6 DFP对染铝大鼠心肌组织损伤恢复的形态学观察
阴性对照组大鼠心肌细胞形态正常,细胞横纹清晰,胞核完整,胞浆嗜酸性染色,肌原纤维排列整齐,无明显病理改变,间质细胞正常。
铝染毒组心肌细胞损伤,心肌细胞间隙增大,细胞横纹模糊不清,间质细胞水肿,心肌纤维水肿明显。
DFP低、中、高剂量组与阳性对照组相比,大鼠心肌细胞结构逐渐恢复正常,且随着DFP剂量的增加,心肌损伤的恢复程度增强。
【结论】
1经胃肠道吸收的铝化合物,可在心肌蓄积,造成心肌细胞损伤,并影响心肌中铁的含量。
2 DFP通过螯合促进铝的排除,从而减轻血清、心肌中的铝负荷。
3 DFP通过促进荷铝大鼠心肌组织中铝的排除,使铝所致的心肌酶谱异常、心肌抗氧化系统损伤及心肌病理损伤得到改善。
4 DFP对染铝大鼠心肌组织中必需元素锌、铁、铜、钙、镁的含量无明显影响,但对血清铁有一定程度的促排作用,因此在使用DFP治疗铝中毒时,注意铁剂的补充。
Objective
With the development of industry and technology, the application of aluminum productions become more and more extensive in daily life. Although aluminum is non-essential elements of human body, the toxicity of aluminum should not be ignored. Studies have shown that aluminum can accumulate in human body and produce chronic toxicity. Furthermore, aluminum is widely distributed in the body, since the different exposure approach, dose and duration of aluminum in the body, the "target" organs are different, and the various organs of the organization will be injured. Heart is the organ pumping blood, heart disease, which caused by a variety of reasons, has aroused more and more widespread concerns. Therefore, the study of aluminum toxicity in the heart is particularly important. At present, eliminating mechanism of aluminum compound which exists in multiple exposure or can be transferred to other organs is undefined, clinical treatment tend to apply aluminum chelating agent to copy with the aluminum load. DFP (deferiprone,1,2-dimethyl-3-hydroxy-4-pyridone) is gradually known for the feature of effective and oral, initially it was applied as an iron chelator. Due to the similar nature of aluminum and iron elements, this study will consider DFP as an aluminum chelating agent in animal experiments, mainly from the DFP in the myocardium and serum aluminum in the row effect on other essential elements and myocardial cells to assess the protective effect of DFP on the heart toxicity.
Methods
1 Animal treatments
35 adult Male Wistar rats were obtained from the animals center of Shandong university, and they were 160～220g of weight upon arrival. The animals were acclimatized to the conditions of the animal room for about 1 week after arrival and were maintained on an adlibitum diet and tap water.
The rats were divided into 5 groups randomly, the negative control group were given 0.9% saline lml/d, others were administered AICl3,5 times one week for 8 weeks. Then the groups except the negative control group were redivided into 4 groups, one of which received the 0.9%saline 1ml/day(positive control), the other three groups were administered at different doses of DFP(13.82,27.44, 54.88mg/kg/day). Two weeks later, the rats were sacrificed by decapitation and the samples were stored frozen in plastic flasks until analysis and the enzymes were determined immediately.
2 Records of body weight and general situation
Weighing body weight per day in order to determine the gavage measurement, rats were observed daily for appetite, mental state, actions, facial expressions and general condition of reaction speed. Weight growth was recorded once a week.
3 Effects of DFP on aluminum chelation in rat's heart and serum
Myocardial tissue of rats in each group were obtained, weight and dissolved with microwave instrument, then we determined Al content in myocardial tissue with graphite furnace atomic absorption spectrophotometry to observe the effect of DFP on aluminum.
Serum of each group were obtained and dissolved with microwave digestion instrument. The levels of serum aluminum were observed by graphite furnace atomic absorption spectrophotometer method to analyze effect of DFP's exclusive aluminum.
4 Effect of DFP on the serum myocardial enzyme
Rats in each group after the last gavage, fasting for 24h, were decapitated blood, the immediate collection of blood into the test tube,3500rpm×10min centrifugal, drawing the upper serum in the E-P tube, immediately AST, LDH and CK according to kit instructions determination.
5 Effects of DFP on antioxidant system in rats'myocardial tissue
Myocardial, lung tissue and serum of rats in each group with a certain amount of normal saline were made into 10% tissue homogenate, the prepared tissue homogenate were used low-temperature centrifuge 3500rpm×10min, the prepared homogenization of the centrifugal clear liquid diluted with saline until determination.
6 Effects of DFP on essential elements in myocardial, lung tissue and serum
Myocardial, lung tissue and serum of rats in each group were obtained, weight and dissolved with microwave instrument. Then the various tissues of rats with copper, zinc, calcium, iron and magnesium were analyzed by flame atomic absorption spectrometry to exposed effects of DFP on essential element.
7 Effects of DFP on rats'myocardial tissue damage morphology
Rats heart tissue in each group hematoxylin-eosin staining (HE) staining for pathological observation, aluminum on rat heart cells in morphological changes and the role of DFP on their resume were observed.
Results
1 Records of body weight and the general situation
Rats in negative group were in good condition, well eating, thick and shiny coat, bright eyes, responsive, flexible movement, muscular flexibility; in the first 4 weeks, rats with narcotics showed matte coat, poor response and motility; A small number of rats in middle and high dose group showed skin redness, sweating and other phenomena, days later they were not unusual. Rats in each group were body weight growth, but no significant differences in the rate.
2 Effects of DFP on aluminum chelation in rats
After administration of AICl3 for 8 weeks, significant accumulation of Al in heart tissue of Al-only was observed in comparison with negative control rats (P<0.01).
The treatment of DFP administration significantly decreased the aluminum content in comparison to the positive control group.
Aluminum exposure levels of serum aluminum content was higher than the negative control group (P<0.01), high-dose DFP group and decreased serum aluminum, but is still high compared with the negative control group (P<0.01).
3 DFP on the serum myocardial enzyme of rats
In the experiment, the level of LDH in serum of al-only group were significantly increased (P<0.01). While, after the treatment with DFP, the level in serum decreased singnificantly (P<0.01).
CK is also a marker enzyme of heart injury, an increased level was found in positive group (P<0.01), the treatment with Lower dose DFP and median dose DFP were not significantly decreased, but the level of CK in higher dose of DFP decreased significantly (P<0.01).
However, in this study, the results did not show any significantly difference in AST. So Al accumulation do not affect the level of AST in serum, and DFP is still no harm to the AST.
4 Effects of DFP on antioxidant system in myocardial tissue
The tissue levels of MDA in Al-only animals increased siginificantly compared to the animals in the negative control group(P<0.01), and decreased significantly in animals with the median and high doses of DFP treatment comparing to the positive control animals (P<0.05, P<0.01).
In the present study, the effects of DFP on antioxidant system which were damaged by aluminum were performed in.
The level of GSH-Px in positive control group was found decreased obiviousely. However, the level of antioxidant enzyme GSH-Px increased significantly under three different doses. There was no change in overall T-SOD level was achieved between groups.
5 Effects of DFP on other essential elements
The comparison of the content of essential element in the myocardium between groups is illustrated. It shows that the decrease the content of iron, while, DFP was found effective in reducing heart Al, and recovering the Fe.
Al-exposed rats serum Fe lower than the negative control group (P<0.05), in which high-dose group reduced DFP (P<0.05).
However, it shows that there was no difference of Cu, Zn, Mg and Ca between groups.
6 Effect of DFP on myocardial tissue damage morphology
Negative control group rats myocardial cells in morphologically normal cells, a clear cross striations, nucleus integrity, eosinophilic cytoplasm stained myofibrils arranged in neat rows, no obvious pathological changes in the normal stromal cells.
Al-exposed group of myocardial cell injury, myocardial cells, gap increased, cell stripes and blurred staining increased eosinophilic cytoplasm, nucleus condensation, fragmentation. Myofibrils distorted, mesenchymal cells edema, a small number of muscle cells broken.
In lower, medium and high-dose DFP group myocardial interstitial gradually reduced, the structure of rat myocardial cells gradually returned to normal.
Conclusion
1 The aluminum compounds can be accumulated in the myocardium, which can result in myocardial cell injury and affect the myocardial iron content..
2 DFP promotes aluminum exclusion by chelating, thereby reduces aluminum load in serum and myocardium, so that makes the myocardial cell injury recover gradually.
3 DFP improves biochemical indicators and myocardial pathological changes, such as myocardial enzymes, peroxides enzymes caused by aluminum, by means of promoting the exclusion of aluminum in myocardial tissue of rats carrying aluminum,
4 DFP has no effect on the content of essential elements, Zn, Fe, Ca, Mg, and Cu, of the heart organs of rat dyeing of aluminum, but has some exclusive effect on the element Fe in serum to a certain degree, so in the DFP treatment of aluminum intoxication, the supplement of iron should be attention.
铝是人体非必需元素,因此对铝的毒性的研究不容忽视。研究表明,铝在体内分布广泛,且在人体内蓄积并产生慢性毒性,根据暴露的途径、剂量和持续时间不同,铝在体内的“靶”器官也不同,因此其对组织及各个器官都将造成损伤。心脏是体内的泵血器官,心脏疾病引起了人们越来越多地普遍关注。因此研究铝的心脏毒性显得尤为重要。目前,重复暴露或潜在转移到其他组织的铝复合物的清除机制尚不明确,但在临床上多使用螯合剂来治疗机体金属中毒。DFP(deferiprone,1,2-二甲基-3-羟基-4-吡啶酮)以口服有效的显著特点逐渐被认识,最初被作为一种铁螯合剂,由于铝和铁的元素性质相近,本研究将DFP作为一种铝螯合剂进行动物实验,通过对心肌和血清铝的测定,心肌酶谱、心脏抗氧化系统及心、肺、血清中其他必需元素等指标的研究来评价DFP对染铝大鼠心脏毒性的保护作用。
【方法】
1实验动物处理
选用健康成年雄性Wistar大鼠,体质量160～220g,自由进水、进食。平衡一周后,按体质量随机分为5组,即阴性对照组、阳性对照组、DFP低剂量组、DFP中剂量组、DFP高剂量组。除阴性对照组外,其余各组均以灌胃方式给予氯化铝(AlCl3)染毒,阴性对照组给予相应剂量的生理盐水。每周给药5次,平衡2天后继续给药。染毒8周后,DFP低、中、高剂量组分别给予不同剂量的DFP,阴性对照组和阳性对照组给予相应剂量的生理盐水,持续2周。
2大鼠一般情况及体重的记录
每天称量大鼠体重,以确定灌胃剂量,每天观察各组大鼠的食欲、精神状态、行动、眼神及反应速度等一般状况。每周记录一次体重增长情况。
3 DFP对染铝大鼠心肌、血清铝的促排作用
取各组大鼠心肌组织及血清,用微波消解仪消化后,使用石墨炉原子吸收分光光度法测定心肌组织及血清中铝含量,观察DFP的排铝效果。
4 DFP对染铝大鼠血清心肌酶谱的影响
各组大鼠最后一次灌胃给药后,禁食禁水24h,断头取血,立即收集血液到试管中,3500rpm离心10min,吸取上层血清于E-P管中,立即依照试剂盒使用说明分别进行血清中乳酸脱氢酶、肌酸激酶、谷草转氨酶的测定。
5 DFP对染铝大鼠心肌组织抗氧化系统的影响
取各组大鼠心肌组织,加入一定量的生理盐水制备成10%组织匀浆,将制备好的组织匀浆用低温离心机3500rpm离心10min,取上清液,根据需要用生理盐水稀释后,进行脂质过氧化物丙二醛、超氧化物歧化酶、谷胱甘肽过氧化物酶的测定。
6 DFP对染铝大鼠心、肺组织及血清中必需元素的影响
取各组大鼠心、肺组织及血清用微波消解仪消化后,采用火焰原子吸收分光光度法进行组织中铜、锌、钙、铁、镁含量的测定。
7 DFP对染铝大鼠心肌组织损伤恢复的形态学观察
取各组大鼠心脏组织苏木素-伊红(HE)染色,进行病理学观察,观察铝对大鼠心肌细胞的病理形态学改变及DFP对其恢复作用。
【结果】
1大鼠一般情况及体重的记录
阴性对照组大鼠一般情况良好,进食良好,被毛浓密而有光泽,反应灵敏,动作灵活,肌肉有弹性。前4周染毒大鼠多数表现为被毛无光泽,反应迟缓,活动力较差；中、高剂量组给予DFP前两天有少数出现皮肤发红、出汗等现象,以后均未出现异常。各组大鼠体重均增长,但增长幅度未见明显差异。
2 DFP对染铝大鼠心肌、血清铝的促排作用
与阴性对照组比较,阳性对照组大鼠心肌中铝含量升高(P＜0.01),给予DFP治疗后,低、中、高剂量组与阳性对照组比较,铝含量均降低(P＜0.05,P＜0.01),且DFP中、高剂量组与阴性对照组中铝含量无差异(P＞0.05)。
阳性对照组血清铝含量较阴性对照组升高(P＜0.01),给予DFP后,DFP高剂量组血清铝含量降低(P＜0.01),但与阴性对照组相比仍较高(P＜0.01)。
3 DFP对染铝大鼠血清心肌酶谱的影响
各组大鼠血清心肌酶活力测定结果显示,阳性对照组乳酸脱氢酶、肌酸激酶的活力高于阴性对照组(P＜0.01)。在给予DFP后,高剂量组肌酸激酶活力低于阳性对照组(P＜0.01),但与阴性对照组相比未见明显差异(P＞0.05)；低、中、高剂量组乳酸脱氢酶的活力与阳性对照组相比降低(P＜0.01),但与阴性对照组比较无差别(P＞0.05)。
4 DFP对染铝大鼠心肌组织抗氧化系统的影响
各组大鼠心肌组织中丙二醛、谷胱甘肽过氧化物酶、超氧化物歧化酶的测定结果显示,与阴性对照组相比,阳性对照组心肌组织脂质过氧化产物丙二醛的含量升高(P＜0.01),谷胱甘肽过氧化物酶活力降低(P＜0.01)；给予DFP后,中、高剂量组丙二醛含量与阳性对照组相比明显降低(P＜0.05),低、中、高剂量组谷胱甘肽过氧化物酶的活力与阳性对照组相比明显升高(P＜0.01),且均与阴性对照组无差异(P＞0.05)。
5 DFP对染铝大鼠心、肺组织及血清中必需元素的影响
阳性对照组大鼠心肌铁含量较阴性对照组降低(P＜0.05),DFP低、中、高剂量组大鼠心肌中铁含量高于阳性对照组(P＜0.05),且与阴性对照组比较无差异(P＞0.05)；
阳性对照组大鼠血清铁含量低于阴性对照组(P＜0.05)；给予DFP后,低、中剂量组血清铁含量无明显变化,但DFP高剂量组血清铁含量低于阳性对照组(P＜0.05)。
各组大鼠心、肺组织及血清中铜、锌、钙、镁的含量比较差异均无统计学意义(P＞0.05)。
6 DFP对染铝大鼠心肌组织损伤恢复的形态学观察
阴性对照组大鼠心肌细胞形态正常,细胞横纹清晰,胞核完整,胞浆嗜酸性染色,肌原纤维排列整齐,无明显病理改变,间质细胞正常。
铝染毒组心肌细胞损伤,心肌细胞间隙增大,细胞横纹模糊不清,间质细胞水肿,心肌纤维水肿明显。
DFP低、中、高剂量组与阳性对照组相比,大鼠心肌细胞结构逐渐恢复正常,且随着DFP剂量的增加,心肌损伤的恢复程度增强。
【结论】
1经胃肠道吸收的铝化合物,可在心肌蓄积,造成心肌细胞损伤,并影响心肌中铁的含量。
2 DFP通过螯合促进铝的排除,从而减轻血清、心肌中的铝负荷。
3 DFP通过促进荷铝大鼠心肌组织中铝的排除,使铝所致的心肌酶谱异常、心肌抗氧化系统损伤及心肌病理损伤得到改善。
4 DFP对染铝大鼠心肌组织中必需元素锌、铁、铜、钙、镁的含量无明显影响,但对血清铁有一定程度的促排作用,因此在使用DFP治疗铝中毒时,注意铁剂的补充。
Objective
With the development of industry and technology, the application of aluminum productions become more and more extensive in daily life. Although aluminum is non-essential elements of human body, the toxicity of aluminum should not be ignored. Studies have shown that aluminum can accumulate in human body and produce chronic toxicity. Furthermore, aluminum is widely distributed in the body, since the different exposure approach, dose and duration of aluminum in the body, the "target" organs are different, and the various organs of the organization will be injured. Heart is the organ pumping blood, heart disease, which caused by a variety of reasons, has aroused more and more widespread concerns. Therefore, the study of aluminum toxicity in the heart is particularly important. At present, eliminating mechanism of aluminum compound which exists in multiple exposure or can be transferred to other organs is undefined, clinical treatment tend to apply aluminum chelating agent to copy with the aluminum load. DFP (deferiprone,1,2-dimethyl-3-hydroxy-4-pyridone) is gradually known for the feature of effective and oral, initially it was applied as an iron chelator. Due to the similar nature of aluminum and iron elements, this study will consider DFP as an aluminum chelating agent in animal experiments, mainly from the DFP in the myocardium and serum aluminum in the row effect on other essential elements and myocardial cells to assess the protective effect of DFP on the heart toxicity.
Methods
1 Animal treatments
35 adult Male Wistar rats were obtained from the animals center of Shandong university, and they were 160～220g of weight upon arrival. The animals were acclimatized to the conditions of the animal room for about 1 week after arrival and were maintained on an adlibitum diet and tap water.
The rats were divided into 5 groups randomly, the negative control group were given 0.9% saline lml/d, others were administered AICl3,5 times one week for 8 weeks. Then the groups except the negative control group were redivided into 4 groups, one of which received the 0.9%saline 1ml/day(positive control), the other three groups were administered at different doses of DFP(13.82,27.44, 54.88mg/kg/day). Two weeks later, the rats were sacrificed by decapitation and the samples were stored frozen in plastic flasks until analysis and the enzymes were determined immediately.
2 Records of body weight and general situation
Weighing body weight per day in order to determine the gavage measurement, rats were observed daily for appetite, mental state, actions, facial expressions and general condition of reaction speed. Weight growth was recorded once a week.
3 Effects of DFP on aluminum chelation in rat's heart and serum
Myocardial tissue of rats in each group were obtained, weight and dissolved with microwave instrument, then we determined Al content in myocardial tissue with graphite furnace atomic absorption spectrophotometry to observe the effect of DFP on aluminum.
Serum of each group were obtained and dissolved with microwave digestion instrument. The levels of serum aluminum were observed by graphite furnace atomic absorption spectrophotometer method to analyze effect of DFP's exclusive aluminum.
4 Effect of DFP on the serum myocardial enzyme
Rats in each group after the last gavage, fasting for 24h, were decapitated blood, the immediate collection of blood into the test tube,3500rpm×10min centrifugal, drawing the upper serum in the E-P tube, immediately AST, LDH and CK according to kit instructions determination.
5 Effects of DFP on antioxidant system in rats'myocardial tissue
Myocardial, lung tissue and serum of rats in each group with a certain amount of normal saline were made into 10% tissue homogenate, the prepared tissue homogenate were used low-temperature centrifuge 3500rpm×10min, the prepared homogenization of the centrifugal clear liquid diluted with saline until determination.
6 Effects of DFP on essential elements in myocardial, lung tissue and serum
Myocardial, lung tissue and serum of rats in each group were obtained, weight and dissolved with microwave instrument. Then the various tissues of rats with copper, zinc, calcium, iron and magnesium were analyzed by flame atomic absorption spectrometry to exposed effects of DFP on essential element.
7 Effects of DFP on rats'myocardial tissue damage morphology
Rats heart tissue in each group hematoxylin-eosin staining (HE) staining for pathological observation, aluminum on rat heart cells in morphological changes and the role of DFP on their resume were observed.
Results
1 Records of body weight and the general situation
Rats in negative group were in good condition, well eating, thick and shiny coat, bright eyes, responsive, flexible movement, muscular flexibility; in the first 4 weeks, rats with narcotics showed matte coat, poor response and motility; A small number of rats in middle and high dose group showed skin redness, sweating and other phenomena, days later they were not unusual. Rats in each group were body weight growth, but no significant differences in the rate.
2 Effects of DFP on aluminum chelation in rats
After administration of AICl3 for 8 weeks, significant accumulation of Al in heart tissue of Al-only was observed in comparison with negative control rats (P<0.01).
The treatment of DFP administration significantly decreased the aluminum content in comparison to the positive control group.
Aluminum exposure levels of serum aluminum content was higher than the negative control group (P<0.01), high-dose DFP group and decreased serum aluminum, but is still high compared with the negative control group (P<0.01).
3 DFP on the serum myocardial enzyme of rats
In the experiment, the level of LDH in serum of al-only group were significantly increased (P<0.01). While, after the treatment with DFP, the level in serum decreased singnificantly (P<0.01).
CK is also a marker enzyme of heart injury, an increased level was found in positive group (P<0.01), the treatment with Lower dose DFP and median dose DFP were not significantly decreased, but the level of CK in higher dose of DFP decreased significantly (P<0.01).
However, in this study, the results did not show any significantly difference in AST. So Al accumulation do not affect the level of AST in serum, and DFP is still no harm to the AST.
4 Effects of DFP on antioxidant system in myocardial tissue
The tissue levels of MDA in Al-only animals increased siginificantly compared to the animals in the negative control group(P<0.01), and decreased significantly in animals with the median and high doses of DFP treatment comparing to the positive control animals (P<0.05, P<0.01).
In the present study, the effects of DFP on antioxidant system which were damaged by aluminum were performed in.
The level of GSH-Px in positive control group was found decreased obiviousely. However, the level of antioxidant enzyme GSH-Px increased significantly under three different doses. There was no change in overall T-SOD level was achieved between groups.
5 Effects of DFP on other essential elements
The comparison of the content of essential element in the myocardium between groups is illustrated. It shows that the decrease the content of iron, while, DFP was found effective in reducing heart Al, and recovering the Fe.
Al-exposed rats serum Fe lower than the negative control group (P<0.05), in which high-dose group reduced DFP (P<0.05).
However, it shows that there was no difference of Cu, Zn, Mg and Ca between groups.
6 Effect of DFP on myocardial tissue damage morphology
Negative control group rats myocardial cells in morphologically normal cells, a clear cross striations, nucleus integrity, eosinophilic cytoplasm stained myofibrils arranged in neat rows, no obvious pathological changes in the normal stromal cells.
Al-exposed group of myocardial cell injury, myocardial cells, gap increased, cell stripes and blurred staining increased eosinophilic cytoplasm, nucleus condensation, fragmentation. Myofibrils distorted, mesenchymal cells edema, a small number of muscle cells broken.
In lower, medium and high-dose DFP group myocardial interstitial gradually reduced, the structure of rat myocardial cells gradually returned to normal.
Conclusion
1 The aluminum compounds can be accumulated in the myocardium, which can result in myocardial cell injury and affect the myocardial iron content..
2 DFP promotes aluminum exclusion by chelating, thereby reduces aluminum load in serum and myocardium, so that makes the myocardial cell injury recover gradually.
3 DFP improves biochemical indicators and myocardial pathological changes, such as myocardial enzymes, peroxides enzymes caused by aluminum, by means of promoting the exclusion of aluminum in myocardial tissue of rats carrying aluminum,
4 DFP has no effect on the content of essential elements, Zn, Fe, Ca, Mg, and Cu, of the heart organs of rat dyeing of aluminum, but has some exclusive effect on the element Fe in serum to a certain degree, so in the DFP treatment of aluminum intoxication, the supplement of iron should be attention.
引文
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