The Protective Effects Of Various Experimental Treatments Approach On The Cachexia Mice Associated Weight Loss

Cancer cachexia is a multifactorial host wasting syndrome,which is characterized by anorexia and progressive weight loss.Despite the continuous improvement of cancer treatment methods,there is a relative lack of effective treatments for cachexia,and so far,there is no approved FDA drug for cancer cachexia.Therefore,finding safe and effective treatment methods are the key points of cachexia prevention and treatment.The pathological basis of the formation of cachexia is due to the disorder of nutrition metabolism.In order to explore the feasibility of the treatment of cachexia based on the regulation of nutritional metabolism,aiming at the imbalance of energy metabolism and the insufficiency of food intake,we analyzes and studies the protective effect of creatine and pentoxifylline(PTX)targeting peripheral metabolic organs,the melanocortin receptor antagonists and cannabinoid receptor agonists targeting the metabolic centers,on cachexia mice.This study is divided into three parts.The first part mainly discusses the protective effect of creatine on the weight of mice with cachexia.Our study found that in the animal model of cachexia,creatine had a significant protective effect on the weight of cachexia mice.By HE staining,it was found that creatine had a relatively obvious protective effect on the degradation of skeletal muscle and the loss of fat in cachexia mice.The molecular pathological mechanism of creatine-protected muscle degradation and fat loss was studied by Western blot to detect the key regulators of muscle atrophy and fat loss.All these was proved that increasing the energy supply of cells can inhibits the activation of skeletal muscle degradation pathways and improve the pathological phenotype of cachexia.In the second part,we studied the protective effect of PTX,an antiinflammatory cytokine phosphodiesterase inhibitor,and found that PTX can significantly alleviate the weight loss of cachexia mice.Furthermore,we detected the protein expression levels related to muscle atrophy and fat loss by Western blot,and found that PTX has a relatively weak protective effect on muscle degradation in cachexia mice,but the protective effect of PTX on fat loss is more obvious,indicating that the protective effect of PTX on cachexia is mainly aimed at the loss of fat.In the third part,we investigate whether drugs that increase appetite under central nerve stimulation can improve cachexia-related pathological phenotypes.The effects of SHU9119,an antagonist of melanocortin receptor(POMC neuron),and WIN55212-2,an agonist of cannabinoid receptor,on the weight loss of cachexia mice were studied.It was found that the above-mentioned drugs did not significantly improve the body weight of cachexia mice.By analyzing the protective effect of the above drugs on the body weight of cachexia model mice,we can further clarify the pathogenesis of cachexia,screen and identify the prevention and treatment targets,and provide experimental basis.