The mechanistic study on Wa medicine Niang-Mu-Liang medicinal liquor mitigating diabetes mellitus erectile dysfunction in rats by inhibiting ferroptosis

Background:This study aims to investigate the therapeutic effect of Wa medicine Niang-Mu-Liang medicinal liquor(NML)on rats with diabetes mellitus erectile dysfunction(DMED)and its impact on the ferroptosis signaling pathway.Methods:Thirty Sprague-Dawley rats were randomly divided into three groups:Control,DMED,and NML.After establishing the DMED model,treatments were administered for 8 weeks.After the administration,apomorphine hydrochloride tests were conducted to measure the mass and organ index of testes and epididymides,sperm concentration and viability in each group.Penile corpus cavernosum tissues were stained with hematoxylin and eosin.Nitric oxide and cyclic guanosine monophosphate levels in the penile corpus cavernosum tissues were determined using biochemical kits and enzyme-linked immunosorbent assay,while the expression of proteins related to the ferroptosis signaling pathway was measured by Western blot.Results:Compared to the DMED group,the DMED rats treated with NML showed significantly increased erection frequency,testicular and epididymal mass and index,sperm count and viability,along with noticeable improvement in the pathological morphology of penile corpus cavernosum.The content of nitric oxide and cyclic guanosine monophosphate,and the expression of ferritin heavy chain,ferritin light chain,and glutathione peroxidase 4 proteins in penile corpus cavernosum tissue were elevated,while the expression of transferrin and STEAP3 proteins was reduced.Conclusion:NML can improve erectile function in DMED rats by inhibiting the ferroptosis signaling pathway.

Mechanism of the Xuefu Zhuyu decoction in treating diabetes mellitus erectile dysfunction based on the CaSR/Gq-PLC-PKC pathway

Background:To investigate the mechanism of Xuefu Zhuyu decoction in the treatment of diabetes mellitus erectile dysfunction.Methods:Rats with diabetes mellitus erectile dysfunction were developed using streptozocin and randomly assigned into model,low-dose herbal,and high-dose herbal groups.All rats were administered normal saline or the corresponding drugs by oral gavage for 4 weeks.The related indices were detected using enzyme-linked immunosorbent assays,immunohistochemistry,western blotting,and transmission electron microscopy.Results:The levels of lectin-like oxidized low-density protein receptor-1,endothelin-1,NADH oxidase,vascular cell adhesion molecule-1,and intercellular adhesion molecule-1 in the model group were significantly higher than they were in the mock group but lower than they were in the herbal treatment group.The level of nitric oxide was lower in the model group than was in the mock group but higher than the level in the herbal treatment group.The calcium-sensitive receptor,phospho-protein kinase Cδ/protein kinase Cδ,phosphorylated c-Jun amino-terminal kinase/c-Jun amino-terminal kinase,and phospho-P38 mitogen-activated protein kinase/P38 mitogen-activated protein kinase expression levels in the model group were higher than were in the mock group but lower than were in the herbal treatment group.The structures of the Corpus cavernosum penis endothelial cells were significantly improved in the herbal treatment group than they did in the model group.Conclusion:Xuefu Zhuyu decoction can decrease injury to the endothelium,improve vascular endothelial diastolic and contractive function,and inhibit vascular fibrosis in rats with diabetes mellitus erectile dysfunction.This mechanism may be related to the CaSR/Gq-PLC-PKC pathway.

STUDY ON HEMODYNAMICS OF ERECTION IN DIABETIC ERECTILE DYSFUNCTION

Objective To study the cavernosa hemodynamics in diabetic erectile dysfunction ( ED).Methods 22 diabetic and 35 psychic ED patients were studied by intracavernosum injection of a mixture papaver-ine and phentolamine (30/1mg) to assess the hemodynamics changes of the corpus cavernosum by means of colour duplex ultrasonography. Results The average hemodynamics data of the diabetic ED patients vs that of the psy-chogenic ED patients in terms of peak flow velocity (PFV):20. 06±7.15cm/s vs 35. 82±9. 41cm/s, end diastolic velocity (EDV) : 8. 82±0. 35cm/s vs 5. 51±0. 42cm/s,artery diameter (Ad) : 0. 78±0. 25cm vs 1. 01±0. 42cm, vein diameter ( Vd) : 1.05±0. 32mm vs 1.21±0. 45mm, resistance index(RI) : 0. 72±0. 28 vs 0. 98±0. 31,mean velocity of artery (MV):6. 71±0. 27cm/s vs 10. 31±3. 32cm/s, dorsal deep vein flow(DDVF) : 28. 81±6. 32cm/ s vs 25. 74±0. 58cm/s. Stasticstical differences existed in PFV, Ad,RI and MV(P <0. 01). The arterial wall is thick and rigid in diabetic ED patients. Conclusion Atheroscleorsis and veno-occlusive dysfunction of the corpus cavernosum are essential to the development of diabetic ED.

Relationship between Gut Microbiota and Type 2 Diabetic Erectile Dysfunction in Sprague-Dawley Rats

In order to investigate the relationship between gut microbiota and type 2 diabetic erectile dysfunction（T2DED）, we analyzed the characteristics of gut microbiota in the Sprague-Dawley（SD） rats with T2DED. Thirty-five SD rats were randomly divided into two groups： control group（n=15） with normal diet, and experimental group（n=20） with construction of T2D model. Faecal and serum samples were collected at 2nd and 8th week after establishment of T2D model, respectively. Faecal samples were used for analysis of gut microbiota, and serum samples for detection of trimethylamine N-oxide（TMAO）, lipopolysaccharide（LPS）, and inflammatory factors like interleukin-1（IL-1）, IL-2, IL-10, and monocyte chemoattractantprotein-1（MCP-1）. The main compositions of gut microbiota were Bacteroidetes, Proteobacteria and Firmicutes at the phylum level, and Oscillospira, Allobaculum, Bacteroides, Ruminococcus, SMB53, Prevotella, Coprococcus, Sutterella and Blautia at the genus level with relatively higher abundance in all SD rats. The relative abundance of Enterococcus, Corynebacterium, Aerococcus, Facklamia（opportunistic pathogens in most case） increased, and that of Allobaculum, Bifidobacterium, Eubacterium, Anaerotruncus（beneficial bacteria） decreased in T2DED group as compared with that at 2nd week after establishment of T2D model（T2D2 group）. The serum contents of TMAO, LPS, IL-1, IL-2, IL-10 and MCP-1 in T2DED group were significantly higher than those in control group. The gut microbiota of T2DED rats was inhibited. The gut microbiota of T2DED rats had changed, as the relative abundance of beneficial bacterium was decreased while that of opportunistic pathogens was increased. The variations of gut microbiota might lead to inflammation and prompt the emergence of erectile dysfunction in the rats with T2D. TMAO might play an important role in the formation of T2DED.

Nitro-oleic acid ameliorates erectile dysfunction in a streptozotocin-induced rat model of diabetes by inhibiting oxidative stress and apoptosis and activating the NO/cGMP pathway

The major vascular complications associated with diabetes make the management of diabetic mellitus erectile dysfunction(DMED)a challenging endeavor.Notable factors contributing to DMED include oxidative stress,nitric oxide(NO)/cyclic guanosine monophosphate(cGMP)pathway activation,and apoptosis,while nitro-oleic acid(NO,-OA)has been shown to be beneficial in treating these aspects of this condition.We,herein,investigated the effects and possible mechanisms of NO,-OA on erectile function as assessed in a streptozotocin-induced rat model of diabetes.Our results revealed that the erectile function of DMED rats was significantly impaired compared with that of the control group.However,in response to 4 weeks of NO,-OA treatment,there was an improvement in erectile function.The expression of oxidative stress-related indicators was significantly increased and the NO/cGMP pathway was impaired in the DMED group.The expression of proapoptotic factors was increased,while that of antiapoptotic factors was decreased in the DMED group.Moreover,the cell morphology in the cavernous tissue of the DMED group also changed adversely.NO,-OA treatment significantly reversed all these changes observed in the DMED group.In conclusion,NO,-OA treatment partially improved erectile function in DMED rats through mechanisms that included inhibition of oxidative stress,activation of the NO/cGMP pathway,and a reduction in apoptosis.