GlcNAc Affects The MAPKs Pathway Of Cavernosal Smooth Muscle Cells And Its Effect On Erectile Function In Rats

Erectile dysfunction(ED),also known as impotence,is a typical male sexual dysfunction disease,mainly due to the initiation and maintenance difficulties of penile erection.Foreign studies have shown that 52% of 40-70 years old Men have varying degrees of ED with an annual incidence of 25.9/1000.Our country's research also shows that the prevalence of erectile dysfunction in men over 40 years old is 40.2%,and in recent years there is a trend of high incidence and young age,which may be related to people's increasing awareness of the quality of life,but at the same time,with the recent life The level of improvement,the gradual westernization of the diet structure,the accelerated pace of life,obesity,high blood pressure,diabetes and other high-year trends,the penis as a functional organ affected by both mental and organic factors,the impact is also increasing year by year.At present,it is believed that the erection of the penis is mainly achieved by activating the NO/cGMP/PKG pathway,and the phosphodiesterase inhibitor represented by sildenafil can reduce the activity of PDE5 and reduce the hydrolysis of cGMP in penile smooth muscle cells to maintain the penis.The role of smooth muscle relaxation.In addition,studies on NO synthesis damage,oxidative stress,endothelin(ET)and receptors,RhoA/Rho pathway,nerve damage and hormones have shown that these factors do not fully explain the occurrence of erectile dysfunction.In recent years,more and more studies have shown that O-glycosylation may play an important role in the occurrence of ED.O-glycosylation was first discovered in 1984 by Johns Hopkins University,GW Hart,etc.,and has been an important research hotspot because of the uniqueness and functional importance of this glycosylation form.Like many post-translational protein modification processes,such as phosphorylation,acetylation,and ubiquitination,it is a complex and basic physiological process in the body.It plays an important role in many biological processes and has important biological functions.It is involved in a number of importantbiological processes such as gene expression,signal transduction,immune protection,viral replication,cell growth and differentiation,cell adhesion,protein degradation,and inflammation.O-glycosylation participates in a series of complex cellular activities such as signal transduction,gene transcription,protein translation,cellular response,and protein degradation in a mechanism similar to phosphorylation.In this study,the primary penile smooth muscle cells were cultured and the HBP pathway intermediate GlcNAc was added to the cells to determine the effect of drugs on the mitogen-activated protein kinases(MAPKs)pathway.The MAPKs pathway mainly includes the extracellular signal-regulated kinase(ERK)pathway,the c-Jun N-terminal kinase(JNK)pathway and the p38 signaling pathway.Studies have shown that changes in the MAPKs pathway It has important biological significance for regulating penile erection.Therefore,the interaction of GlcNAc with MAPKs protein in corpus cavernosum smooth muscle cells may have new guiding significance for us to improve the level of ED treatment.The main results and conclusions of this experiment are as follows:1.GlcNAc inhibits the MAPKs pathway of rat cavernosal smooth muscle cells through an O-glycosylation-dependent pathway.The primary model of rat CSMC was successfully constructed.It was found that GlcNAc can significantly increase the total O-glycosylation level of the protein in cells(P<0.05),and further studies found that it can inhibit ERK mainly through glycosylation-dependent pathway.Phosphorylation levels of the P38 MAPKs pathway(P<0.05),but did not affect the total expression level of protein.2.GlcNAc increased the O-glycosylation level of rat corpus cavernosum smooth muscle cells significantly(P<0.05),but it was not found to have significant effects on erectile function,sex hormone,CSMC fibrosis level and metabolic function.IHC studies have found that GlcNAc can increase the level of O-glycosylation in cavernous smooth muscle tissue,but Masson staining did not find statistically significant differences in fibrosis levels compared with controls.In addition,ICP/MAP studies showed that Compared with the healthy rats,the penile erectile function of rats fed GlcNAc was decreased,but the difference was not statistically significant.Studies of GlcNAc on changes in body weight and blood glucose in rats also showed no significant differencefrom the control group.3.GlcNAc can be used as an effective tool for studying O-glycosylation.Experiments have shown that GlcNAc can significantly increase the O-glycosylation level of rat corpus cavernosum smooth muscle(P<0.05)regardless of intragastric feeding or cell culture.This study provides a new study for O-glycosylation.tool.In summary,GlcNAc can be used as a new means to study O-glycosylation,which significantly improves the O-glycosylation level of rat cavernosal smooth muscle cells,and can significantly inhibit the phosphorylation of MAPKs pathway in cells.It can provide important reference for further study of mechanisms affecting erection.In addition,preliminary studies have shown that GlcNAc has not been found to have an effect on erectile function in rats,which is different from diabetic rats,but a downtrend was found in research,therefor,more evidence is needed for the final conclusion.In the past,ED research focused on NO/cGMP/PKG and other pathways.However,molecular mechanism research seems to have encountered bottlenecks in recent years.In order to better understand the mechanism of action of ED,this target may provide us with new ideas for improving the level of ED treatment and direction.