| Diabetes mellitus(DM),a metabolic disease caused by a synergy of complex and multi-factors,is considered a global public health problem that imposes a significant financial burden on healthcare systems worldwide and negatively impacts on quality of life.In recent years,the incidence of diabetes has increased dramatically due to the frequent intake of high-calorie diets and the prevalence of inactive lifestyle in society.Currently,adverse effects due to synthetic drugs were emerged in the clinical setting referring to anti-diabetes.Therefore,effective and less toxic anti-diabetic components from natural products were gained much attention.The genus Ganoderma atrum with the potential of hypoglycemic has been proved to be able to alleviate the impact of hyperglycemia and insulin resistance.Ganoderma atrum polysaccharide(PSG)is a water-soluble active component extracted from Ganoderma atrum.The biological activities of PSG have been widely reported,including antioxidant,anti-inflammatory,anti-aging,anti-tumor and immunity strengthening effects.However,there were few studies on the protective effect of PSG on complications involved in diabetic myocardial injury.Therefore,this study established type 2 diabetes mellitus(T2DM)model of rats that was induced by the combination of high-glucose and high-fat diet,along with the urea-streptozotocin(STZ)and further explored the myocardial injury in rats.Briefly,the myocardial protection effects of PSG were reflected from three aspects of oxidative stress,inflammation,gut microbiota,and the metabolites of gut microbiota.The main contents and results of presently study are summarized as follows:1.Explore the anti-diabetic effects of PSG: T2 DM model was established by high-glucose and high-fat diet combined with low dose STZ(30mg/kg bw).The general situation of the rats was observed,and the pancreatic injury was reflected by HE staining,fasting plasma glucose levels(FBG),blood lipid,glucose tolerance and insulin resistance were measured,respectively.The results showed that PSG could effectively improve the symptoms of polydipsia and polyuria when compared to the diabetic rats without any treatment,as evidence by preventing from weight loss,and restoring the mental state of diabetic rats.Moreover,PSG could significantly alleviated hyperglycemia and hyperlipidemia in T2 DM,and reduced insulin resistance level induced by hyperglycemia,hyperlipidemia and STZ.Meanwhile,PSG improved the function of pancreatic ? cells by maintaining the normal morphology and structure of pancreatic tissue,suggesting that PSG has anti-diabetic function.2.The protective effects of PSG on myocardial injury and its possible mechanism were explored: The pathological changes of myocardium were observed by HE staining.Serum lactate dehydrogenase(LDH)in T2 DM was determined,and the activities of antioxidant enzymes superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),catalase(CAT),malondialdehyde(MDA)and inflammatory cytokines IL-1? and IL-6 in myocardium of T2 DM were detected.Subsequently,the protein expression of nuclear factor E2-related factor 2(Nrf2),NLRP3,Capase-1 was analyzed.The results suggested PSG could prevent the damage of myocardial tissue and reduce the release of LDH into the blood in diabetic rats.PSG significantly increased the level of tissue antioxidant enzymes by up-regulating the Nrf2 signaling pathway,and inhibited oxidative stress in the myocardium of T2 DM.In addition,the level of myocardial inflammation was alleviated by inhibiting the inflammatory signaling pathway NLRP3/ Caspase-1 /IL-1? T2 DM rats by the treatment of PSG.These results suggested that PSG might play a protective role by inhibiting oxidative stress and inflammation in the myocardium of diabetic rats.3.The modification effect of PSG on gut microbiota disorder were investigated in T2 DM rats: The effect of PSG on intestine of T2 DM rats was examined by HE staining and immunohistochemistry.High-throughput sequencing technology was employed to analyze the effects of PSG on gut microbiota of T2 DM rats.Furthermore,the contents of short chain fatty acids(SCFAs)in feces,lipopolysaccharide(LPS)and trimethylamine-N-Oxide(TMAO)in serum were detected.PSG could improve the morphological and structural damage of intestinal tissue caused by diabetes,and up-regulate the expression of zonula occludens 1(ZO-1)protein to maintain the integrity of intestinal mucosal barrier.Moreover,PSG regulated the relative abundance of Bacteroidetes,Prevotella and CF231,Meanwhile,the relative abundance of Lactobacillus,Roseburia,Oscillospira,Ruminococcus,Coprococcus and Bifidobacterium were up-regulated to alleviate the dysregulation of gut microbiome in diabetic rats.Therefore,PSG could enhance the content of SCFAs,and inhibit the increase of LPS and TMAO.Collectively,these results indicated that PSG could play a beneficial role in myocardium by inhibiting gut microbiota dysregulation and intestinal permeability,as well as the abnormal increase of LPS,TMAO and propionic acid,and promoting the production of other SCFAs.In addition,PSG could exert myocardial protection by increasing NRF2-mediated antioxidant level and inhibiting NLRP3/ caspase-1/IL-1? signaling pathway mediated inflammation level.The increase of LPS and TMAO could aggravate myocardial injury.Therefore,this study speculated that inhibition of the secretion of LPS and TMAO might be one of the ways that PSG plays a protective role in myocardium. |
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