The Protective Effects Of Kisspeptin Against The Impairment Induced By Heat Stress In Rats Hypothalamus

Stress is a non-specific systemic reactions which can disrupt the metabolic balance of internal environment.Thermal stress and thermal damage,mainly happened in hot weather,can lead to heat stroke,heart failure,oxidative stress and inflammation,which bring serious harm for the human production and the development of animal husbandry.The hypothalamus is the nerve center for the regulation of body temperature,but there is no sufficient evidence to clarify the mechanism of hypothalamus in body temperature regulation.Related studies have shown that the hypothalamus damage is the main cause for the body dysfunction,rather than caused by the body damage directly.Kisspeptin is a neuropeptide encoded by the gene of KISS-1 and the studies have shown that it play an important role in reproductive regulation and tumor metastasis.The latest research suggest that Kisspeptin also have the function in antioxidative mechanism.Heat stress can damage the whole neurodocrine immune system,so a single changes of physical and chemical indicator can not reflect the whole changes of the body while metabonomics is the research method which can observe the changes of metabolites after the body were stimulated by stress.Metabolomics can reflect the result of interaction between genetic and environmental on the overall level,and it is an important part in development of functional genomics and system biology.Based on GC/TOF-MS technique,this experiment study the function of Kisspeptin in hypothalamus of rat induced by heat stress systematically by using metabonomics method.This experiment establish the model of thermal stress based on metabonomics,by using GC/TOF-MS technique to determine the changes of metabolites in hypothalamus of rats after heat stress.The results shown that amino acids,fatty acids and single amine neurotransmitter metabolites in the hypothalamus were significantly increased in the heat stress group,and the change of metabolites were same with the change of HPA axis and HPG axis after heat stress.D-Ribose,an important energy source of the hypothalamus,is significantly reduced.The change of suger metabolites in hypothalamus indicated the disorder of glucose metabolism,while the increase of amino acid show that amino acid as an compensatory protection mechanism to adjust glucose metabolic disorder caused by heat stress.Compared with heat stress group,the amino acids,fatty acids and single amine neurotransmitter metabolites in the hypothalamus were significantly decreased in Kisspeptin group,while the D-ribose was increased obviously.The results show that after the injection of Kisspeptin,the injury of hypothalamus caused by heat stress were relieved and the metabolic disorder of amino acids,fatty acids were repressed and the glycometabolism return to mormal.The adrenal,thymus and spleen index were significantly lower after heat stress(P<0.01).Compared with heat stress group,the thymus and adrenal gland index were significantly higher in Kisspeptin group(P<0.05).The activity of T-AOC,SOD and GSH-PX were significantly decreased after heat stress(P<0.05),while the level of MDA were significantly increased(P<0.05).Compared with heat stress group,the activity of T-AOC,SOD and GSH-PX were significantly increased(P<0.05),while the level of MDA were significantly decreased(P<0.05).In the metabolites of hypothalamus,arachidonic acid changed obviously in each group.The papers reported that arachidonic acid play an important role in the inflammatory response.HETEs,EETs and PGs,as the downstream metabolites of arachidonic acid,also play an important role in the oxidative stress.The genes of CYP4A2,CYP2C12 and COX are the key genes in generate the HETEs,EETs and PGs in arachidonic acid metabolism.The genes of CYP4A2,CYP2C12 were increased significantly in heat stress group while COX1 and COX2 decreased obviously(P<0.05).Compared with heat stress group,the gene of COX1 increased significantly(P<0.05),while CYP4A2 and CYP2Cl2 decreased obviously(P<0.05).HETE plays an important role in promoting inflammation while the EETs and PGs has an important role in anti-inflammation.Above the results,the damage were apparent after heat stress and the body were injured in all aspects while the damage were relieved after the intervention of Kisspeptin.Based on metabonomics method,This experiment confirmed that Kisspeptin can alleviate the injury induced by heat stress in hypothalamus and inferred the mechanism of Kisspeptin in antioxidative stress at the level of gene and protein.