Cyclophosphamide is a multifunctional alkylating agent,which is widely used in the treatment of cancer and some non-malignant diseases.However,cyclophosphamide causes many side effects leading an irreversible damage to the body.Ganoderma lucidum polysaccharide is an important active substance in Ganoderma lucidum with many functional properties such as anti-oxidation,immune regulation,liver protection and intestinal barrier repair,which has broad application prospects.In order to avoid the loss of Ganoderma lucidum polysaccharide in transmembrane transport into the organism and ensure its maximum utilization in the body,the material selected in the experiment is waxy corn starch-Ganoderma lucidum polysaccharide complex (RS-GLP).The objective of the paper is to explore the mechanism of the inhibition of cyclophosphamide-induced side effects by using RS-GLP,providing a basis for the wide application of Ganoderma lucidum polysaccharides and their complexes.In order to simulate the metabolism of complexes in human body,the subject carried out animal experiments.All animals were divided into five groups:normal group (NC),model group (MC),low dose intervention group (LPC),high dose intervention group(HPC),and high dose control group (HP).The low-dose and high-dose groups were given 75 mg/Kg and 150 mg/Kg RS-GLP for 7 days.On the 7th day,one-time high-dose cyclophosphamide (200 mg/Kg) was injected to the rats of the MC group,the LPC group,and the HPC group.The changes of body weight,immune organ index,oxidative stress,liver function index,liver histopathological changes,liver oxidative stress,inflammation and other related gene expression and intestinal microbial composition were observed.The analysis shows that RS-GLP can alleviate the weight loss of rat caused by cyclophosphamide,inhibit the decline of thymus index of spleen index,illustrating that it has protective effect on immune organs.RS-GLP inhibited cyclophosphamide-induced oxidative stress by up-regulating the expression of Nrf2 and HO-1 in the liver and down-regulating the expression of NF-kB,Bax and Casp3.The serum malondialdehyde(MDA) content in the intervention group decreased,and the superoxide dismutase activity(T-SOD) increased.At the same time,RS-GLP down-regulated the expression of TNF-α,IL-6,IL-4,INF-γ , reduced tissue inflammation,and reduced liver damage caused by cyclophosphamide.RS-GLP intervention reduced serum alanine aminotransferase (ALT)and alkaline phosphatase activity (AKP),alleviating the disorder of hepatocytes in the model group.The results of 16sRNA showed that RS-GLP increased the diversity of intestinal flora and improved the abundance of beneficial bacteria which are anti-inflammatory and beneficial to intestinal health.In summary,RS-GLP can inhibit the side effects of cyclophosphamide in a number of ways.However,the optimal dosage should be further explored. |