Protective Effect Of Isatis Root Polysaccharide On Injuries Induced By Lead Acetate In Mice

Lead is a kind of widely used,but also the main toxic pollution of the environment.With the rapid development of industry,transportation and urban residents,the health threat of lead pollution to animals and human beings has been paid more attention.Although there are many reports about the toxicity of lead to animals,but still lacks of a evaluation of comprehensive and systematic toxicity of multiple organ.Its mechanism is not yet clear.How to research and develop effective,non-toxic side effects of Chinese herbal medicines,to effectively prevent and control animal lead poisoning,is still an urgent matter for domestic and foreign scholars.Objective: This paper studied the protective effect of IRPS on injuries induced by acetate in mice.A mouse model of lead induced-injury was established to observe the protective effect of IRPS on the growth performance and multiple organs of lead induced mice,further more,the mechanism of liver protection from oxidative stress mediated mitochondrial apoptotic pathway was also discussed.Method: Sixty healthy male Kunming mice at the age of 3 weeks were randomly divided into six groups,each treatment with 10 mice.The control group(group A),lead induced model group(group B),individual 100 mg/kg IRPS group(group C),lead + low,medium and high dose IRPS treatment group(group D,E and F,50,100,200 mg/kg·BW).Lead induced model of mice was prepared by intraperitoneal injection of 20 mg/kg·BW lead acetate with for 7 d.After the model was established,the treatment group of IRPS was given different concentrations of IRPS,1 times a day and for 28 d.During the trial,the total intake of food was recorded every day and weighed 1 times a week.The daily feed intake,body mass growth and the organ coefficient of each group were calculated.Paraffin sections of the liver,duodenum and heart were made to observe the histopathological changes.Determination of liver and kidney function related biochemical indexes in serum by automatic blood biochemical analyzer.The liver tissue levels of MDA,SOD,(GSH-Px),CAT were detected;the expression of Bax,Bcl-2,Caspase-9,Caspase-3 protein were detected by western blotting;TUNEL method of paraffin section was used to detect the apoptosisof liver cells.The experimental data were analyzed by SPSS17.0.Results:(1)The result indicated that the lead could greatly decreased the mice average daily feed intake,whereas the IRPS treatment groups average daily feed intake increased significantly with the increase of IRPS dose.(2)Compared with the control group,the weight of mice in the lead treatment groups were significantly decreased(P<0.05 or P<0.01).IRPS could promote the recovery of body mass in mice,and the 100 mg/kg IRPS treated group increased significantly(P<0.05)from 3th week.(3)Compared with the control group,in addition to the kidney index decreased significantly(P<0.05)in model group mice,liver index is increased,but no significant difference(P>0.05).Compared with the model group,50 mg/kg IRPS treatment group testicular index and 100 mg/kg IRPS treatment group liver index were significantly lower(P<0.05),whereas 100 mg/kg IRPS treatment group kidney index significantly increased(P<0.05).(4)Lead acetate can significantly change the normal morphology of liver,duodenum and heart,while IRPS can improve the pathological damage of lead induced tissue.(5)Compared with the lead induced group,the MDA content in the liver of IRPS treatment group was significantly reduced(P<0.05 or P<0.01).In addition,IRPS could promote the recovery of GSH-Px and SOD activity but not CAT.(6)WB results showed that IRPS could protect liver cells from lead induced apoptosis by increasing the ratio of bcl-2/bax and decreasing the ratio of cleaved to caspase-3/caspase-3.(7)TUNEL results show that lead can promote the apoptosis of liver cells,while IRPS plays a protective role in the apoptosis of liver cells induced by lead,and the best dose is 100 mg/kg IRPS.Conclusion: The above results indicate that 100 mg/kg IRPS can promote the growth and development of mice,repair the injury of liver,duodenum and heart caused by lead,and reduce the oxidative stress of liver induced by lead and decrease the apoptosis of hepatocytes.These findings reveal a potential protective capability of IRPS against lead-induced oxidative stress via mitochondrial mediated signal pathway.