Role Of Hepcidin In Nerve Damage Of Rats Induced By Nano-pbs And Lead Acetate Exposure

Objectives To investigate the role of hepcidin in hippocampus and cortex oxidative damage induced by nano-pbs and Pb Ac exposure. Our founding will enrich the mechanism of lead induced neurotoxicity and provide for the prevention and treatment base for nerve damage by nano-pbs and Pb Ac exposure.Methods 1 Experimental animals and grouping: 30 SD pregnant rats were randomly divided into 3 groups, namely the control group, nano-pbs group and lead acetate(Pb Ac)group. Pregnant rats in nan-pbs group were given 10 mg/Kg nano-pbs by oral, and pregnant rats in Pb Ac group were given 100 mg/Kg Pb Ac by oral and rats in control group were given same amount saline. When the offspring rats were grown 21 days after birth, they were weaned and continue to give corresponding lead processing as their mother until 42 days after birth. 2 Morris water maze test was used to detect pups learning and memory performance. 3 The lead and iron content of hippocampus and cortex of pups was determined by ICP-MS. 4 Flow cytometry was applied to determine the ROS content. 5 ELASA was applied to detect the AGEs,hepcidin and IL-6 content.Meanwhile, the ability of restrain the hydroxy radical produce in hippocampus and cortex were measured. 6 Perls’ staining method was used to observe cortex and hippocampus iron distribution. 7 RT-PCR was applied to analysis the Hepcidin m RNA content in cortex and hippocampus. 8 HE staining to observe the pathological changes in rat brains.Statistical analysis: All data were showed sx ±. The statistics methods include ANOVA,LSD and correlation analysis. P<0.05 was considered statistically significant.Results 1 Impact of nano-pbs and PbAc exposure on offspring rats. 1) The navigation time of pups in nano-pbs and Pb Ac exposure at PND 21, PND 42 were longer than the control group(P<0.05). Meanwhile, times of crossing platform were less than the control group(P<0.05). 2) The ROS content in PND1, PND21, PND42 pups’ cortex and hippocampus were higher than control group, and with the exposure time extended, the ROS levels in PND21, PND42 rats’ cortex and hippocampus by nano-pbs exposure group were higher than Pb Ac group, the difference was statistically significant. 3) The AGEs content were higher than control group in PND1, PND21,PND42 pups’ cortex and hippocampus, the difference was statistically significant(P<0.05); Compared with Pb Ac group, the AGEs content in PND21 and PND42 rats cortex and hippocampus were statistically significant difference by nano-pbs exposure. 4) Compared with control group, the ability of restrain the hydroxy radical ability in rats cortex and hippocampus were reduced by Pb Ac exposure. After nano- pbs exposure, the ability of anti-hydroxy radical ability in rats hippocampus were reduced, and compared with Pb Ac group difference was statistically significant. 5) Compared with control group, after the nanopbs and Pb Ac exposure the pups’ hippocampus and cortical neurons appear to the number of neuron degeneration reduced and necrosis, neurons arranged in disorder. 2 The nano-pbs and Pb Ac exposure resulted in lead and iron content increase in pups cortex and hippocampus. 1) nano-pbs and Pb Ac exposure, the lead levels were higher than control group in PND1, PND 21, PND 42 rats’ cortex, hippocampus, the difference was statistically significant(P<0.05); and lead levels in hippocampus were higher than in the cortex. 2) After Pb Ac exposure, the hepcidin content in PND1, PND21 and PND42 pups’ cortex were respectively(7.64±1.53) μg/g,(33.74±5.55) μg/g,(46.62±8.70) μg/g, in hippocampus were respectively(66.67±20.94) μg/g,(103.48±20.66) μg/g,(47.73±5.62)μg/g. After nano-pbs exposure, the hepcidin content in PND1, PND21 and PND42 pups’ cortex were respectively(6.39±0.69) μg/g,(32.63±6.03) μg/g,(46.20±10.69) μg/g, in hippocampus were respectively(164.72±25.92) μg/g,(128.73±21.35) μg/g,(56.92±4.37)μg/g, higher than those of the control group(P<0.05); Compared with Pb Ac group, the iron content in hippocampus that nano-pbs group was statistically significant difference.The staining of Perl’s shows that there are many iron deposit in PND1, PND21, PND42pups’ cortex and hippocampus, and with the extention of time, the stating significantly enhanced. Correlation analysis results showed that iron content were positively correlated with lead content, navigation time and AGEs content in pups’ cortex and hippocampus by Pb Ac exposure. After nano-pbs exposure, the iron content were positively correlated with lead content, navigation time and AGEs content in pups’ cortex and hippocampus.3 The hepcidin, hepcidin m RNA and IL- 6 changed in cortex and hippocampus by nano-pbs and Pb Ac exposure. 1) After Pb Ac exposure, the hepcidin content in PND1, PND21 and PND42 offspring cortex of control group respectively increased 1.40, 1.56, 2.00 folds,1.42, 1.22, 140 folds c. After nano-pbs exposure, the hepcidin content in PND1, PND21 and PND42 pups’ cortex of control group respectively increased 1.57, 2.05, 2.34 folds,1.54, 1.45, 1.60 folds increased in hippocampus. And the hepcidin content in PND21 and PND42 rats cortex and hippocampus of nano-pbs group were higher than that Pb Ac group. The result shows that after nano-pbs and Pb Ac exposure, the express of hepcidin m RNA in cortex and hippocampus were higher than that of control group, and the difference was statistically significant. 2) After nano-pbs and Pb Ac exposure, the IL-6content were higher than control group in the PND1, PND21 and PND42 pups’ cortex and hippocampus, and the difference was statistically significant(P<0.05).Conclusions 1 Nano-pbs and Pb Ac exposure can induce of oxidative damage in pups’ cortex and hippocampus, and oxidative damage of cortex and hippocampus of nano-pbs exposed pups are higher than that of Pb Ac exposure. 2 The expression of hepcidin involve in the oxidative damage in pups’ cortex and hippocampus.