| Objective To explore the potential mechanism of the effect of high-fat diet(HFD)on erectile function,and observe the change of gut microbiota in HFD mice.To investigate the effect of HFD on erectile function.Methods:(1)Twenty 10-month-old male SD rats were randomly divided into normal diet control group(n = 10)and HFD model group(n = 10).After 4 months of feeding,the levels of body weight,blood glucose and blood lipid were measured.Erectile function was measured by max intracavernous pressure(ICP)/ mean arterial pressure(MAP)to explore the effect of HFD on erectile function.Hematoxylin-eosin(H&E)staining was used to observe the pathological changes of liver and corpus cavernosum tissues.Masson's Trichrome staining was used to observe the degree of cavernous fibrosis.The expressions of TNF-? and IL-6 proteins in corpus cavernosum were detected by immunohistochemistry(IHC).The expressions of phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT),nuclear factor-kappa B(NF-?B),tumor necrosis factor-?(TNF-?)and interleukin-6(IL-6)proteins in corpus cavernosum were detected by Western blot.(2)Twenty 9-month-old KM mice were randomly divided into a control group(n = 10)and a model group(n = 10).They were fed continuously for 2 months to prepare an obesity model,and the composition of their gut microbiota was detected by 16 S r RNA.The changes of bacterial metabolites was detected by GC-MS.Results:(1)The level of FBG in the model group showed no significant difference(P > 0.05).The levels of body weight,serum total cholesterol(TCH),triglyceride(TG)and low-density lipoprotein cholesterol(LDL-C)were significantly increased in model group(P < 0.05).The levels of high-density lipoprotein cholesterol(HDL-C)were decreased in model group(P < 0.01).ICP/MAP was significantly reduced(P < 0.001).H&E staining showed that liver tissues were obvious steatosis,continuous interruption of cavernosum smooth muscle cells(CSMCs)and endothelial cells(ECs);Masson's Trichrome staining showed that the smooth muscle were decreased,cavernous fibrosis increased.IHC showed that the expression levels of TNF-? and IL-6 in corpus cavernosum were significantly increased(P < 0.01).Western blot showed that the expression levels of PI3 K,AKT,NF-?B,TNF-? and IL-6 in corpus cavernosum were significantly increased(P < 0.05).(2)16S r RNA sequencing analysis showed that the abundance of Firmicutes were decreased(P < 0.001),and the abundance of Bacteroidetes were increased(P < 0.001)compared with Control group at the phylum level.At the genus level,the abundance of Lactobacillus,Bifidobacterium,et al.were decreased(P < 0.05),and the abundance of AF12,Streptococcus and Erysipelotrichaceae,et al.were increased(P < 0.05)in Model group.Metabolomics analysis screened and characterized 32 differential substances.Compared with the control group,16 substances decreased and 16 substances increased in the model group;HFD had a significant effect on the flora-host co-metabolic pathway;correlation analysis showed: Lactobacillus showed a high positive correlation with aminobutyric acid,glucaric acid and arabinose,and a high negative correlation with isoleucine,threonine,aspartic acid,cholic acid and valine;Bifidobacterium showed a higher positive correlation with glycolic acid,3-hydroxypyridine and glucaric acid,but a higher negative correlation with valine.Streptococcus showed high positive correlation with tryptophan,proline and pyroglutamic acid;AF12 showed high negative correlation with tryptophan;Erysipelotrichaceae showed high negative correlation with putrescine.Conclusion: HFD may lead to elevated levels of inflammatory factors,which can cause CSMCs and ECs dysfunction,and eventually increase the risk of erectile dysfunction(ED)in rats.HFD can cause gut microbiota diversity and its metabolic products to change,which may lead to the activation of metabolic pathways related to inflammation and increase the body's inflammation level.Maintaining the homeostasis of the gut microbiota plays an important role in maintaining the health of the host. |
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