| Objective To explore the influence of manganese treatment on the inflammatory response and learning and memory ability in rats and the protection by sodium para-amino salicylic acid. Methods 120 male SD rats were divided into 6 groups according to the weight after fed to adapt the environment for a week. They are 4 weeks animal experiment groups (normal control group and Mn-exposed group) and 8 weeks animal experiment groups (normal control group, Mn-exposed group, PAS intervention group and PAS control group).There are 20 rats in each group.4 weeks animal experiment:the Mn-exposed group received intraperitoneal injection (i.p.) of 15 mg/kg MnCl2·4H2O and the normal control group i.p. the same volume physiological saline. The rats in 4 weeks animal experiment received treatment for 5 days a week for 4 weeks for simulating working time of workers.8 weeks animal experiment:the Mn-exposed group and received intraperitoneal injection (i.p.) of 15 mg/kg MnCl2·4H2O. The PAS intervention group received intraperitoneal injection (i.p.) of 15 mg/kg MnCl2·4H2O and then received back subcutaneous injection(s.c.) of 160 mg/kg PAS-Na. The normal control group received i.p. the same volume physiological saline and PAS control group received physiological saline in the same volume. The rats in 8 weeks animal experiment received treatment for 5 days a week for 8 weeks for simulating working time of workers. At the end of the infected or treatment, the Morris water maze experiment was proceeded to determined the ability of learning and memory of rats (10 rats were randomly selected in each group). After the Morris water maze experiment, the rats were immediately put to death (euthanasia). The blood samples were acquired by drawning from the heart. The hippocampus were rapid separation on the ice. The manganese contents in the blood were determinated by graphite furnace atomic absorption spectrometry. The inflammatory factor levels (TNF-a, IL-1β, IL-6 and PGE2) in the blood and hippocampus were detected by enzyme-linked immunosorbent assay. The levels of IL-lp,IL-6, COX2, TNF-a and iNOS mRNA in hippocampus were detected by PCR method. The levels of positive cells expression of GABA, GFAP, BCL-2/BAX and Caspese3 were determinated immunohistochemical method. Results (1) The swimming distance and escape latency of Mn-exposed group increased compared with the control group rats (P<0.05). After the intervene of PAS-Na, the swimming distance and escape latency of Mn-exposed group decresed (P<0.05). The wear ring numbers and the third quadrant in spatial memory time percentage and the third like distance limit percentage of Mn-exposed group increased compared with the control group rats (P<0.05)and the PAS-Na has the protective effects. (2) The levels of Mn in the blood increased after Mn exposure (P<0.05) and the blood Mn has the time dose effect relationship with the Mn exposure time. And the PAS-Na decreased the blood Mn levels (P<0.05), (3) The contents of serum IL-1β,IL-6,PGE2 and TNF-a increased after Mn exposure (P<0.05) and the PAS-Na decreased the inflammatory factors (P<0.05). (4) The levels of IL-1β,IL-6,PGE2 and TNF-a in the hippocampus increased after Mn exposure (P<0.05) and the PAS-Na decreased the inflammatory factors in the hippocampus (P<0.05). (5) The concentrations of IL-1β,IL-6, COX2, TNF-a and iNOS mRNA in hippocampus increased obviously in the Mn-exposed group (P<0.05). And the PAS-Na has the reverse effect (P<0.05). (6) The levels of positive cells expression of GFAP and Caspese3 increased obviously in Mn-exposed group (P<0.05), and the BCL-2/BAX Ratio decreased (P<0.05). And the PAS-Na has the reverse effect (P<0.05). Conclusion Excessive manganese exposure may cause the weight grow slow, viscera coefficient increased (heart, liver, spleen and kidney), learning and memory ability decresed, the blood Mn levels increased, serum and hippocampus inflammation factor expression quantity increased and the PAS-Na has the reverse effect. |
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