| [Objective]Aluminum is widely distributed in nature and the content of soluble aluminum in nature increases year after year with the development of industrial process and the changes of natural environment conditions, so that the human body is able to contact and absorb more and more aluminum into the body. Aluminum can accumulate in the human organs of brain, kidney, liver, bone and other tissues and cause chronic toxic effect. Nervous system is extremely sensitive to aluminum and it is one of the main target organs of aluminum toxicity, it is considered that Alzheimer’s disease (AD), Parkinson’s disease (PD) and other nervous system diseases are associated with the accumulation of aluminum in the nervous system. Aluminum can cause nerve system toxicity in the both direct and indirect ways. Taurine is abundant in brain and plays an important role in promoting the normal development of the nervous system, in nutrition of nerve fibers and in regulating the osmotic pressure and so on. Deferiprone (DFP) has a good eliminating effect to aluminum. In this experiment, Wistar rats were chosen as experimental objects, and aluminum chloride was administered in the way of lavage to establish the chronic aluminum poisoning model, then we made use of single and combined taurine and DFP for treatment. In the latter stage, we observed and determined the behavioral performance, enzymes related to neurotransmitter, the contents of amino acids and single amine neurotransmitters, the contents of some essential elements to explore the improvement effects of taurine and DFP to aluminum induced cognitive impairment of learning and memory in rats.[Methods]1. Experimental animalsWe selected 70 of Male Wistar rats weight at 175g-215g as experimental objects, and they were randomly divided into 7 groups according to the weight:control group, aluminum exposed group, taurine intervention group, DFP low-dose intervention group, DFP high-dose intervention group, taurine+DFP low-dose intervention group and taurine+DFP high-dose intervention group,10 in each group. The rats were administrated in the intragastric way 6 days 1 week. The whole experimental process lasted for 8 weeks, the first 4 weeks for exposed stage, the second 4 weeks for detoxification stage. The rats of the control group were given saline for 1.0 ml/d lasting for 8 weeks; Aluminum exposed group were given 281.40 mg/(kg·d) AlCl3·6H2O in the first 4 weeks, and 1.0 ml/d saline in the second 4 weeks; Taurine intervention group were given 281.40 mg/(kg·d) AICl3·6H2O in the first 4 weeks, and 400 mg/(kg·d) taurine in the second 4 week; DFP low-dose intervention group were given 281.40 mg/(kg·d) AICl3·6H2O in the first 4 weeks, and 13.82 mg/(kg·d) DFP in the second 4 week; DFP high-dose intervention group were given 281.40 mg/(kg·d) AICl3·6H2O in the first 4 weeks, and 27.64 mg/(kg·d) DFP in the second 4 week; Taurine+DFP low-dose intervention group were given 281.40 mg/(kg·d) AICl36·H2O in the first 4 weeks, and 400mg/(kg d) taurine in the morning and 13.82 mg/(kg·d) DFP in the afternoon in the second 4 week; Taurine+DFP high-dose intervention group were given 281.40 mg/(kg·d) AlCl3·6H2O in the first 4 weeks, and 400mg/(kg ·d) taurine in the morning and 27.64 mg/(kg·d) DFP in the afternoon in the second 4 weeks. The Morris water maze experiment was carried after the administration stage and rats were killed by decapitation at the end of the experiment with fasting of 24 hours. The brain were collected and saved in the temperature of -80℃。2. General growth and development status of ratsWe observed the mental state, athletic ability and the growth of hair of rats every day during the experiment, also we weighed the rats in the 3 and 6 day in every week. The brain of the rats were also weighed for calculating the coefficient of brain tissue.3. Morris water maze experimentMorris water maze experiment was carried out after the administration stage. The Experiment is divided into two stages:training stage and testing stage. The total distance and the incubation period were measured and recorded in the training stage; the number of crossing the platform was measured and recorded in the testing stage.4. Determination of the activity of acetylcholinesterase (AChE) and nitric oxide synthase (NOS) in brain of ratsWeighed accurately appropriate amount of brain and made of 10% brain homogenate with saline (m (g):V (ml)= 1:9), then we determined the activities of AChE and NOS in accordance with the kit.5. Determination of the contents of aluminum and some essential elements in rat brainWeighed accurately appropriate amount of brain and cut into pieces, then the rat brain was digested by microwave digestion instrument. After the digestion, the digestion solutions were diluted into samples to be determined.6. Determination of the contents of monoamine neurotransmitters in the brain of ratsWeighed accurately appropriate amount of brain and made of 10% brain homogenate with perchlorate solution (0.1 mol/L) (m (g):V (ml)= 1:9), then we determined the contents of noradrenalin(NE), adrenaline(E), dopamine (DA) and serotonin (5-HT) by high performance liquid chromatograph (HPLC) with fluorescence detector.7. Determination of the contents of amino acid neurotransmitters in the brain of ratsWeighed accurately appropriate amount of brain and made of 10% brain homogenate with acetonitrile solution (50%) (m (g):V (ml)= 1:9), then the amino acid neurotransmitters were derived with dinitrofluorobenzene (DNFB). then we determined the contents of Aspartic acid (Asp), glutamate (Glu), glycine (Gly) and aminobutyric acid (GABA) and taurine (Tau) by high performance liquid chromatograph (HPLC) with Diode array detector.[Results]1. Effects of taurine and DFP on general growth of aluminum exposed ratsRats in the control group had a good condition in growth, mental state and have a supple hair during the whole experiment, while rats in aluminum exposed group showed the condition of retarded growth, listlessness and coarse hair phenomenon at the end of the experiment. The body weight of aluminum exposed group was significantly lower than that of the negative control group (P<0.05) since the 6th week. The brain coefficient also showed significant differences between various processing groups. The brain coefficient of aluminum exposed group was significantly higher than that of the negative control group (P<0.05); the brain coefficient of DFP low-dose intervention group, DFP high-dose intervention group, taurine+DFP low-dose intervention group and taurine+DFP high-dose intervention group was significantly lower than that of aluminum exposed group (P<0.05); the brain coefficient of taurine+DFP low-dose intervention group was significantly lower than that of taurine intervention group and DFP low-dose intervention group(P<0.05); the brain coefficient of taurine+DFP high-dose intervention group was significantly lower than that of taurine intervention group(P<0.05).2. Effects of taurine and DFPon the cognitive function of aluminum exposed ratsIn the training stage, the total distance and escape latency of aluminum exposed group was significantly longer than that of the control group (P<0.05); the total distance and escape latency of DFP low-dose intervention group, DFP high-dose intervention group, taurine+DFP low-dose intervention group and taurine+DFP high-dose intervention group was significantly shorter than that of the aluminum exposed group (P<0.05); the total distance and escape latency of taurine+DFP low-dose intervention group and taurine+DFP high-dose intervention group was significantly shorter than that of the taurine intervention group (P<0.05); the total distance and escape latency of taurine+DFP low-dose intervention group was significantly shorter than that of the DFP low-dose intervention group (P<0.05).In the test stage, the number of crossing platform of aluminum exposed group was significantly less than that of the control group (P<0.05); the number of crossing platform of DFP low-dose intervention group, DFP high-dose intervention group, taurine+DFP low-dose intervention group and taurine+DFP high-dose intervention group was significantly more than that of the aluminum exposed group (P<0.05); the number of crossing platform of taurine+DFP low-dose intervention group and taurine+DFP high-dose intervention group was significantly more than that of the taurine intervention group (P<0.05); the number of crossing platform of taurine+DFP low-dose intervention group was significantly more than that of the DFP low-dose intervention group (P<0.05).3. Effects of taurine and DFP on the essential elements of aluminum exposed ratsThe content of aluminum in the cortex of the aluminum exposed group was significantly higher than that of the control group (P<0.05); the content of aluminum in the cortex of taurine intervention group, DFP low-dose intervention group, DFP high-dose intervention group, taurine+DFP low-dose intervention group and taurine+DFP high-dose intervention group was significantly lower than that of the aluminum exposed group (P<0.05); the content of aluminum in the cortex of taurine+DFP low-dose intervention group was significantly lower than that of the DFP low-dose intervention group (P<0.05); the content of aluminum in the cortex of taurine+DFP high-dose intervention group was significantly lower than that of the taurine intervention group and DFP high-dose intervention group (P<0.05).Compared to the control group, there was a significant lower of magnesium, copper and iron and a significant higher of zinc in the cortex of the aluminum exposed group (P<0.05); Compared to the aluminum exposed group, there was a significant higher of copper and iron and a significant lower of zinc in the cortex of the taurine intervention group (P<0.05), there was a significant higher of copper and iron in the cortex of the DFP low-dose intervention group (P<0.05), there was a significant higher of magnesium copper and iron in the cortex of the DFP high-dose intervention group, taurine+DFP low-dose intervention group and taurine+DFP high-dose intervention group (P<0.05); Compared to the taurine intervention group, there was a significant higher of copper in the cortex of the taurine+DFP low-dose intervention group and taurine+DFP high-dose intervention group (P<0.05), there was a significant higher of iron in the cortex of the taurine+DFP high-dose intervention group (P<0.05); Compared to the DFP low-dose intervention group, there was a significant higher of copper and a significant lower of zinc in the cortex of the DFP low-dose intervention group (P<0.05).4. Effects of taurine and DFP on the activity of AChE and NOS of aluminum exposed ratsCompared to the control group, there was a significant lower of the activity of NOS and a significant higher of the activity of AChE in the cortex of the aluminum exposed group (P<0.05); Compared to the aluminum exposed group, there was a significant higher of the activity of NOS and a significant lower of the activity of AChE in the cortex of the taurine intervention group, DFP low-dose intervention group, DFP high-dose intervention group, taurine+DFP low-dose intervention group and taurine+DFP high-dose intervention group (P<0.05); Compared to the taurine intervention group, there was a significant higher of the activity of NOS and a significant lower of the activity of AChE in the cortex of the taurine+DFP low-dose intervention group and taurine+DFP high-dose intervention group (P<0.05);Compared to the DFP low-dose intervention group, there was a significant higher of the activity of NOS and a significant lower of the activity of AChE in the cortex of the taurine+DFP low-dose intervention group (P<0.05).5. Effects of taurine and DFP on the contents of monoamine transmitters of aluminum exposed ratsCompared to the control group, there was a significant lower of the contents of NE E DA 5-HT in the cortex of the aluminum exposed group (P<0.05); Compared to the aluminum exposed group, there was a significant higher of the contents of NE DA 5-HT in the cortex of the taurine intervention group (P<0.05), there was a significant higher of the activity of contents of E DA 5-HT in the cortex of the DFP low-dose intervention group (P<0.05), there was a significant higher of the activity of contents of NE E DA 5-HT in the cortex of the DFP high-dose intervention group, taurine+DFP low-dose intervention group and taurine+DFP high-dose intervention group (P<0.05);Compared to the taurine intervention group, there was a significant higher of the contents of E DA in the cortex of the taurine+DFP low-dose intervention group and taurine+DFP high-dose intervention group (P<0.05), there was a significant higher of the contents of 5-HT in the cortex of the taurine+DFP high-dose intervention group (P<0.05);Compared to the DFP low-dose intervention group, there was a significant higher of the contents of NE E in the cortex of the taurine+DFP low-dose intervention group (P<0.05), there was a significant higher of the contents of DA in the cortex of the taurine+DFP high-dose intervention group (P<0.05).6. Effects of taurine and DFP on the contents of amino acid transmitters of aluminum exposed ratsCompared to the control group, there was a significant higher of the contents of Asp Glu and a significant lower of the contents of Gly GABATau in the cortex of the aluminum exposed group (P<0.05); Compared to the aluminum exposed group, there was a significant lower of the contents of Asp and a significant higher of the contents of GABA Tau in the cortex of the taurine intervention group (P<0.05), there was a significant lower of the contents of Asp Glu and a significant higher of the contents of GABA in the cortex of the DFP low-dose intervention group (P<0.05), there was a significant lower of the contents of Asp Glu and a significant higher of the contents of GABA Tau in the cortex of the DFP high-dose intervention group and taurine+DFP low-dose intervention group (P<0.05), there was a significant lower of the contents of Asp Glu and a significant higher of the contents of Gly GABA Tau in the cortex of the taurine+DFP high-dose intervention group (P<0.05);Compared to the taurine intervention group, there was a significant lower of the contents of Asp in the cortex of the taurine+DFP low-dose intervention group and taurine+DFP high-dose intervention group (P<0.05), there is a significant higher of the contents of GABA in the cortex of the taurine+DFP high-dose intervention group (P<0.05); Compared to the DFP low-dose intervention group, there was a significant lower of the contents of Asp in the cortex of the taurine+DFP low-dose intervention group (P<0.05).[Conclusion]1. Both taurine and DFP can improve the growth retardation of aluminum-exposed rats2. Both taurine and DFP can promote drainage of excess aluminum and can regulate the balance of essential elements3. Both taurine and DFP can regulate the activity of neurotransmitter enzyme including AChE and NOS4. Both Taurine and DFP can suppress and improve the disorders of neurotransmitters of aluminum-induced rats5. Both taurine and DFP can improve the cognitive impairment of aluminum-exposed rats6. The combination of taurine and DFP perform a more significant effect than used alone... |
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