| Lanthanum is one of the most widely used rare earth elements.Existing studies have found that lanthanum has neurotoxicity to human body and animals,and lanthanum is often used as a typical rare earth element to study its neurotoxicity Nervous system-related damage induced by environmental pollution caused by lanthanum exposure has attracted more and more attention,and the intestinal flora and nervous system have also been proved to have a close relationship.This study explored the toxicological mechanism of cognitive impairment caused by lanthanum exposure in rats,and explored whether lanthanum exposure has an impact on the nervous system of rats through the influence of intestinal flora,and the impact is related to the cognitive function of rats Whether the barriers are closely relatedObjective:To explore the mechanism of cognitive dysfunction in rats induced by lanthanum exposure through oxidative stress and inflammation of nerve cells induced by cerebral intestinal axis,and to provide theoretical basis for preventing nervous system damage caused by lanthanum exposure.Methods:(1)Animal grouping and treatment: Male Wistar rats were randomly divided into control group,low-dose exposure group,medium-dose exposure group,high-dose exposure group,resveratrol group(10 rats per group).Control group was given the same amount of normal saline every day for 30 days.Low,medium and high dose exposure groups were treated with 10mg/kg,100mg/kg,200mg/kg lanthanum chloride for 30 days.The resveratrol group was given 100mg/kg lanthanum exposure treatment for 30 days and 100mg/kg resveratrol intervention treatment for 16 days.(2)Detection and analysis: The survival rate of weight change was recorded during 30 days of treatment.The water maze experiment was conducted from day 16 to 30 to test the learning and cognitive functions of the rats.Brain tissues were extracted on day 30,and the changes of nerve cells and their ultrastructure were observed by HE staining and transmission electron microscopy.Western blot and immunohistochemistry were used to detect the changes of protein expression related to oxidative stress and inflammation.Feces were extracted and changes in intestinal flora were detected using sequencing of 16 S r RNA gene ampliconsResults:(1)Lanthanum exposure affects oxidative inflammatory response-mediated cognitive dysfunction in rats: compared with control group,survival rate and weight gain of rats decreased with lanthanum exposure concentration.The results of water maze showed that the escape latency and movement distance of rats in exposure group were significantly higher than those in control group,and were proportional to the increase of exposure.HE staining and morphological observation under transmission electron microscopy showed that with the increase of exposure concentration,the damage of nerve cells in the cerebral cortex and hippocampus of rats was also significantly aggravated,which showed that the proportion of necrotic cells was increased,and the mitochondrial score was decreased.Western blot combined with immunohistochemistry showed that with the increase of lanthanum exposure concentration,the expressions of NR-2 and HO-1 in the brain of rats gradually decreased,and the expressions of keap-1 ROS SOD NF-κB NLRP3 ASC IL-1β IL-18 and other factors gradually increased,which had statistical significance(P<0.05).(2)Resveratrol effectively relieved lanthanum exposure mediated nerve damage:compared with lanthanum exposure group,the body weight of rats in the resveratrol group increased,and the water maze results showed that the escape latency and movement distance of rats in the resveratrol group were significantly lower than those in the lanthanum exposure group.HE staining and morphological observation under transmission electron microscopy showed that resveratrol treatment could effectively relieve the damage of nerve cells in the cerebral cortex and hippocampus of rats,and improve the mitochondrial score.Western blot combined with immunohistochemistry confirmed that resveratrol could significantly up-regulate the expression of Nrf-2 and HO-1,and down-regulate the expression of keap-1 ROS SOD NF-κB NLRP3 ASC IL-1β IL-18,which was statistically significant(P<0.05).(3)The brain-gut axis was involved in the nerve damage mediated by lanthanum exposure and the anti-damage process of resveratrol: compared with the control group,lanthanum exposure did not change the composition of dominant flora,but with the increase of exposure concentration,the abundance,species richness,diversity and evenness of different flora significantly changed.Among them,Escherichia＿Shigella,Christensenellaceae＿R＿7＿group and other bacteria were positively correlated with oxidative inflammation-related proteins,while Treponema,Parabacteroides and RF39 were negatively correlated.Compared with lanthanum exposure group,the composition of intestinal flora after resveratrol intervention was more similar to that of control group.Prevotellaceae＿NK3B31＿group,Christensenellaceae＿R＿7＿group and other bacteria were positively correlated with oxidative inflammatory proteins.The bacterial community of UBA1819 and Ruminiclostridium＿9 was negatively correlated.Conclusions:(1)Lanthanum exposure caused intestinal flora disorder in rats,and induced oxidative stress and inflammation through the cerebral intestinal axis,and eventually led to cognitive dysfunction induced by nerve cell damage in rats.(2)The intervention of antioxidant resveratrol,on the basis of restoring the intestinal flora structure of rats,regulates oxidative stress inflammation through the brain and intestinal axis,and effectively alleviates the cognitive dysfunction of rats... |
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