The Effects Of Sodium Para-Aminosalicylate On Pancreatic Injury Induced By Managanese Exposure In Sprague-dawley Rats

Objective To explore the effect of different concentrations of manganese?Mn?exposure on pancreatic injury in SD?Sprague-Dawley?rats and the therapeutic effect on sodium aminosalicylate?PAS-Na?,and to preliminarily study the effect of pancreatic toxicity induced by Mn and the intervention effect of PAS-Na.Methods 120 SD male rats were randomly divided into the Mn exposure and PAS-Na treatment models based on body weight after one week of adaptive feeding.:?1?Establish Mn exposure models?Mn exposed to SD rats in 8 weeks groups?:48 rats were divided randomly into normal control group,low-?medium-?high-dose Mn exposure?L-?M-and H-?,12 SD rats in each group.L-?M-and H-Mn exposure groups were respectively received intraperitoneal injected?i.p.?of MnCl₂·4H₂O solution?5mg/kg,10mg/kg,20mg/kg?.In the meantime,the normal control group were received i.p.of sterile physiological saline once a day,five days per week for 8 weeks.?2?Establish PAS-Na intervention models?Mn exposed to SD rats by PAS-Na in 14 weeks groups?:72rats were divided randomly into normal control group?Mn-treated group?low-?medium-?high-dose PAS-Na-treated?L-?M-and H-PAS-Na?groups with 12 SD male rats in every group.And then,Mn-treated group?L-?M-and H-dose PAS-Na groups were respectively i.p 20mg/kg MnCl₂·4H₂O solution.However,the control group and PAS-Na control group were respectively i.p of isovolumic sterile physiological saline solution.once a day,five days per week for 8 weeks.As well as,L-?M-and H-dose PAS-Na treatment groups and PAS-Na control group were respectively subcutaneous injection?s.c?of PAS-Na?100mg/kg,200mg/kg,300mg/kg,300mg/kg?solution.Meanwhile,the normal control group and Mn-treated group were respectively received s.c of isovolumic sterile physiological saline solution,once a day,five days per week for 6 weeks.The experiment observed indicators:?1?The indicators of growth and development of SD rats were determined:The rats were weighed at a fixed time every week,After Mn exposed or PAS-Na treament,the rats were anesthetized and sacrificed as soon as possible so that rats soft tissue viscera heart,liver,spleen,lung,kidney and other viscera were taken and the viscera coefficient ratio was calculated after weighing.?2?Whole blood Mn concentrations of the SD rats were detected by using graphite furnace atomic flame absorption spectrometry.?3?Pathological sections were used to observe the degree of pancreatic injury caused by Mn exposure and the therapeutic effects of PAS-Na.?4?Serum,pancreatic tissue inflammatory factors and glucose metabolism of rats were measured.?5?The levels of calcium?Ca?,magnesium?Mg?,manganese?Mn?,iron?Fe?,copper?Cu?,zinc?Zn?and selenium?Se?in liver and pancreas were measured by Inductively Coupled Plasma Mass Spectrometry?ICP-MS?.?6?The Pearson's correlation was used in analyzing the relation of serum Mn levels that Mn exposed to rats for 8 weeks and pancreatic or liver mental levels?Ca,Mg,Mn,Fe,Cu,Zn,Se?.Results?1?In the 8 weeks of Mn exposed to rats groups,From the 2nd week to the 8th week,compared with the normal control group,the body weight of L-?M-and H-Mn exposure dose groups increased slower,as well as the difference was statistically significant?P<0.05 or P<0.01?.In the 14 weeks of PAS-Na treatment groups,the body weight of the Mn treated group was still lower than that of the control group?P<0.05 or P<0.01?at the 9th and 10th weeks?treated 1st and 2cd weeks?.?2?In the 8 weeks of Mn exposed to rats groups,compared with the normal control group,liver and kidney coefficients were increased in the H-dose Mn exposure group as well as the difference was statistically significant?P<0.01?.?3?In the 8 weeks of Mn exposed to rats groups,compared with the normal control group,the whole blood Mn levels in the L-?M-and H-dose Mn exposure rats groups were obviously increased and the difference was statistically significant?P<0.05 or P<0.01?.Morever,the higher Mn exposure concentration,the higher blood Mn concentration.In the 14weeks PAS-Na treatment groups,the whole blood Mn levels in the Mn treated group was significantly increased?P<0.01?.At the meantime,compared with the Mn treated group,the whole blood Mn levels in the L-?M-and H-dose PAS-Na treated groups were significantly decreased,as well as the difference was statistically significant?P<0.01?.?4?In the 8 weeks Mn exposed to rats groups,under the optical electon microscope were observed the pancreatic islet and acinar cells had clear structures,neat arrangement and uniform distribution without interstitial edema or inflammatory cells infiltration,with pale pink cytoplasm and dark blue nucleus in the normal control group.The L-dose Mn exposure group had relatively complete glands,acinus celsl edema and loose interstitial.In the M-dose Mn exposure group,the acinar cells edema were obvious and a small number of acinar cells showed vacuolar degeneration or steatosis,losing their normal shape.In the H-dose Mn exposure group showed large areas of coagulative necrosis,infiltration of a large number of inflammatory cells,loose interstitium,destruction of lobular structure,blurred boundaries,massive atrophy and nccrosis of acinar cells,loss of cell contour,visible nuclear shrinkage,fragmentation and dissolution,obvious islet edema,but relatively complete islet cell structure.?5?In the 8 weeks Mn exposed to rats groups,compared with the normal control group,the levels of serum amylase and serum lipase in the L-?M-and H-dose Mn exposure groups were decreased significantly?P<0.05 or P<0.01?,as well as the levels of amylase,IL-1?and TNF-?in the pancreatic tissue of the L-Mn exposure group were increased with statistically significant difference?P<0.05?.In the 14 weeks PAS-Na treatment groups,compared with the normal control group,the content of serum amylase and lipase in the Mn treated group was significantly increased with statistical difference?P<0.05 or P<0.01?.Compared with the Mn treated group,the serum amylase and lipase levels in the L-?M-and H-dose PAS-Na treated groups decreased significantly and the difference was statistically significant?P<0.01?.?6?In the 8 weeks Mn exposed to rats groups,compared with the normal control group,the levels of Mg and Zn in the pancreatic tissue ofM-and H-Mn exposure rats groups decreased,while the levels of Mn in the pancreatic tissue of L-?M-and H-dose Mn exposure groups and the levels of Fe in the pancreatic tissue of M-?H-dose Mn exposure groupsincreased,showing statistical difference?P<0.05 or P<0.01?.In the 14 weeks PAS-Na treatment groups,compared with the normal control group,the contents of Zn in the Mn treated group decreased significantly?P<0.05?.Compared with the Mn treated group,the content of Mn in the L-dose PAS-Na treat group decreased with statistical difference?P<0.05?.?7?In the 8 weeks Mn exposed to rats groups,compared with the normal control group,the levels of Ca and Mn in the liver of H-dose Mn exposure group increased with statistical difference?P<0.05?,the levels of Zn in the liver of L-?M-and H-dose Mn exposure groups increased with statistical difference?P<0.01?.In the 14 weeks PAS-Na treatment groups,the Mn level in the Mn treated group increased with statistical difference?P<0.05?.?8?The correlation between blood Mn levels and the mental levels of pancreas and liver in the 8 weeks rats exposed to Mn:blood Mn levels were positively correlated with pancreatic Mn levels?r=0.635,P<0.01?and liver Mn levels?r=0.613,P<0.05?,while were negatively correlated with pancreatic Mg?r=-0.469,P<0.05?and Zn levels?r=-0.585,P<0.05?.Pancreatic Mg levels were negatvely correlated with Mn levels?r=-0.596,P<0.01?and Fe levels?r=-0.456,P<0.05?,but positively correlated with Zn levels?r=0.569,P<0.05?and Se levels?r=0.468,P<0.05?.Pancreatic Mn levels were positively correlated with Fe levels?r=0.658,P<0.01?,but negatively correlated with Zn?r=-0.620,P<0.01?.Pancreatic Fe levels were negatively correlated with Se?r=-0.533,P<0.05?.Liver Mg levels were positively correlated with Cu levels?r=0.587,P<0.05?Conclusions?1?Excessive Mn exposure may induce growth retardation,as well as increase liver and kidney coefficients in rats.?2?Mn exposure may lead to the increase of whole blood Mn concentration in SD rats,and PAS-Na intervention could reduce whole blood Mn concentration,suggesting that PAS-Na has the effect of prompting the exceretion of Mn.?3?excessive Mn exposure may damage the pancreatic tissue of rats,affecting the normal secretion function of the pancreas,andthe degree of pancreatic damage was related to the dose and time of exposure.?4?PAS-Na may improve pancreatic secretion dysfunction caused by Mn exposure.?5?Mn could accumulate in the pancreas,causing Fe levels increased,but Zn?Mg concentration decreased.Mn also could accumulate in the liver,causing Ca and Zn levels increased.?6?Correlation analysis showed that Mn exposed may caused a part of mentals disorders in pancreas and liver of rats,which may affect the normal physiological metabolism in vivo.