Study On The Mechanism Of Hyperglycemia Induced By Endoplasmic Reticulum Stress In Mice Induced By Nano-titanium Dioxide

Titanium dioxide nanoparticles are a new kind of materials,which have been applied in all walks of life.Nano-titanium dioxide can cause blood glucose metabolic disorder in mice.The recognized mechanism of nano-titanium dioxide toxicity is oxidative stress caused by accumulation of reactive oxygen species.Oxidative stress is an important factor causing blood glucose metabolic disorder.However,in the previous work of this topic,it was found that endoplasmic reticulum stress also participated in the process of nano-titanium dioxide-induced blood sugar elevation.So in the process of nano-titanium dioxide induced blood sugar rise,whether endoplasmic reticulum stress is its main mechanism,or oxidative stress is its main mechanism,or both of them are involved,and whether they are related.It is the key to our research.In this experiment,male mice of ICR strain were given the following treatments: NP group mice were given nano-titanium dioxide of 50 mg/kg body weight;4-PBA group mice were treated with nano-titanium dioxide of 100 mg/kg body weight at the same time as NP group mice,and Cont group mice were given PBS of equal volume.Firstly,the toxicological damage of nano-titanium dioxide(nano-titanium dioxide detection in blood and organs,organ damage and blood glucose metabolism)to mice was investigated after intragastric administration of nano-titanium dioxide.Then,by detecting the accumulation of reactive oxygen species,endoplasmic reticulum stress and the occurrence and time of blood glucose elevation,the time of endoplasmic reticulum stress and reactive oxygen species accumulation was preliminarily determined,and finally through endoplasmic reticulum.After reticulum stress inhibitors inhibited endoplasmic reticulum stress pathway,the accumulation of reactive oxygen species and blood sugar metabolism were observed,and the mechanism of endoplasmic reticulum stress in mice with hyperglycemia induced by nano-titanium dioxide was determined.The results showed that after taking nano-titanium dioxide,Titanium enters the blood first through the digestive system.,then deposited in viscera,and nano-titanium dioxide could cause some damage to various organs of mice;nano-titanium dioxide could cause the blood sugar level of mice in NP group to rise,and the blood sugar value of mice in NP group was significantly higher than that of mice in Cont group,and the increase of blood sugar had nothing to do with body weight and diet.The oral glucose tolerance test showed that the blood glucose level of NP group was significantly higher than that of Cont group,but there was no significant difference in insulin content between NP group and Cont group.It proved that the insulin secretion of NP group was not affected by nanotitanium dioxide.At the same time,endoplasmic reticulum stress,accumulation of reactive oxygen species and metabolic disorders of blood sugar occurred successively in NP mice.It was preliminarily determined that endoplasmic reticulum stress was stimulated before the accumulation of ROS.When 4-phenylbutyric acid(4-PBA)was used to alleviate the stress of endoplasmic reticulum,blood sugar tended to be normal and nano-titanium dioxide-induced ROS was inhibited.These results suggest that nanotitanium dioxide-induced endoplasmic reticulum stress can promote the production of ROS in mice and play a leading role in improving blood sugar in mice.This study provides a new idea for the study of endoplasmic reticulum stress and oxidative stress involved in the process of nano-titanium dioxide-induced blood sugar elevation.