| Objective: Bilirubin is an oxidative end product of heme catabolism and is excreted by liver after glucuronidation by hepatic uridine diphosphate-glucuronyl transferase.Hyperbilirubinemia remains one of the most frequent clinical diagnoses in the neonatal period.Severe hyperbilirubinaemia may progress to acute kernicterus or bilirubin encephalopathy with a significant risk of mortality in newborns Our study is aim to investigate the Permanent effect of hyperbilirubinemia on synaptic plasticity in the dentate gyrus(DG)region of rat hippocampus.Materials and Methods: 7-days old healthy SD rats were randomly divided into control group and experiment groups.When rats are 60 days old,the input/output(I/O)functions,paired-pulse reactions(PPR),excitatory postsynaptic potential(EPSP),and population spike(PS)amplitude were measured in the DG area of two groups of rats in response to stimulation applied to the lateral perforant path.q-PCR and western blot were used to assess the NMDA receptor subunits m RNA expression and protein production in the DG area of two groups.Results: Compared with that in the control rats,the current-voltage curves of both EPSP slope and PS amplitude in experiment rats were significant depressed.The average peak facilitation was 187±16% in control and 164±18% in experiment group(F = 21.054,P =0.000<0.01),respectively.In the control group,the LTP amplitudes were140 ± 3.5% and 242 ± 6%,when estimated from the EPSP slope and PS amplitude,respectively,which were significantly depressed to 124±3.4%(EPSP slope,F =70.489,P =0.00 < 0.01)and138±8.6%(PS amplitude,F = 253.46,P =0.00< 0.01)in the experiment group.Expression level of NMDA receptor subunits protein level(NMDAR-1,NMDAR-2A,NMDAR-2B)of DG areas in experiment rats were 0.146±0.015(NMDAR-1),0.217±0.014(NMDAR-2A)and 0.159±0.015(NMDAR-2B),which were significantly decreased than that in the control rats 0.365±0.049(NMDAR-1),0.432±0.041(NMDA-R2A)and 0.476±0.025(NMDAR-2B)(NMDA-R1:t=4.302,P=0.005<0.01;t=5.004,P=0.009<0.01;NMDAR-2B:t=10.937,P=0.000<0.01)by image analysis of Western Blot;Expression level of NMDA receptor subunits m RNA level(NMDAR-1,NMDAR-2A,NMDAR-2B)of DG areas in experiment rats were 0.7165±0.018(NMDAR-1),0.8000±0.008(NMDAR-2A)and 0.159±0.015(NMDAR-2B),which were significantly decreased than that in the control rats(NMDAR-1:t=13.529 P=0.000<0.01;t=4.048 P=0.000<0.01;NMDAR2A:t=4.048 P=0.000<0.01;NMDAR-2B:t=10.937,P=0.000<0.01)by image analysis of q PCR.Conclusions: These findings suggest that hyperbilirubinemia could induce impairment of synaptic plasticity in rat DG area in vivo,including I/O function,PPR,and LTP,and could reduce NMDAR subunits genes and proteins expression in the DG area of hippocampus which may be closely related to cognitive impairment.Introduction: Jaundice is one of the most common problems encountered in newborn infants,due to immaturity of hepatic conjugation and transport processes for bilirubin.Zinc sulfate may be a promising approach to treat neonatal jaundice.However,the results remain controversial.We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zinc sulfate on hyperbilirubinemia among neonates.Methods: Pub Med,EMbase,Web of science,EBSCO,Cochrane library databases,Ovid,BMJ database,and CINAHL were systematically searched.Randomized controlled trials(RCTs)assessing the effect of zinc sulfate versus placebo on the prevention of jaundice in neonates were included.Two investigators independently searched articles,extracted data,and assessed the quality of included studies.The primary outcomes were total serum bilirubin(TSB)on three days and seven days,the incidence of hyperbilirubinemia.Meta-analysis was performed using random-or fixed-effect models.Results: Five RCTs involving 645 patients were included in the meta-analysis.Overall,compared with placebo,zinc sulfate supplementation failed to significantly reduce TSB on three days(mean difference(MD)= 0.09 mg/d L;95% confidence interval(CI)=-0.49 to 0.67;P= 0.77),TSB on seven days(MD =-0.37 mg/d L;95% CI =-98 to 0.25;P = 0.25)as well as the incidence of hyperbilirubinemia(OR = 1.14;95% CI = 0.74to1.76;P =0.56).Zinc sulfate showed no influence on phototherapy requirement(OR = 0.90;95% CI = 0.41to1.98;P =0.79),but resulted in significantly decreased duration of phototherapy(MD =-16.69 h;95% CI =-25.09 to-8.3 h;P< 0.0001).Conclusions: Zinc sulfate could not reduce the TSB on three days and seven days,the incidence of hyperbilirubinemia and phototherapy requirement,but lead to significantly decreased duration of phototherapy.Zinc sulfate does not reduce TSB and has no beneficial effect on neonatal jaundice.However,zinc sulfate results in significant reduced duration of phototherapy.Neonatal jaundice requiring phototherapy should be administrated with caution.High dose administration and different preparations of zinc salts are needed in future studies. |
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