| Objective: Erectile dysfunction(ED) is one of the most commoncomplications of the diabetes mellitus(DM).Among the male diabeticpatients,there are approximately35%-75%who suffer from differentdegrees of ED.The mechanism of ED caused by diabetes is currentlyunclear and may related to the impaired vascular endothelium, corpuscavernosum smooth muscle(CCSM), peripheral nerveand otherpathogenic factors. Recent research shows that NO/cGMP signalpathway has a key role in the development of diabetic ED.Phosphodiesterase inhibitors (PDE5I) can inhibit the degradation ofcGMP prolong the relaxation time of the penile corpus cavernosum andimprove erectile function. However, the cure rate of the treatment of EDby PDE5I is approximately56%. These indicated that there may beother mechanisms involved in the development of diabetic ED. Theendogenous hydrogen sulfide (H2S) are the third kinds of gaseoussignal molecule after NO and CO, existing widely in human andmammalian organ tissues. Former study showed that H2S play a similarrole in regulating penile erection as NO and CO. H2S is produced bycatalyzing the L-cysteine with cystathionine-beta-synthase (CBS) andcystathionine-gamma-lyase (CSE),which are both dependent on pyridoxal5-phosphate(PLP).In the study,we discussed the effect ofhyperglycemia on H2S signal pathway in rat corpus cavernosum and therelationship between H2S signal pathway and penile erection byinvestigating the expression of CBS and CSE in penile tissue of diabeticrats.Methods: Twenty healthy male Sprague Dawley (SD)rats aged8weeks were randomly divided into four groups: healthy control groupsof4weeks(A) and6weeks(C), diabetes mellitus groups of4weeks(B)and6weeks(D). Streptozotocin was injected intraperitoneally to groupB and D to induce diabetes mellitus while the same volume of normalsaline was injected to group A and C as control. After the establishmentof the diabetic rat model, we measured the serum testosterone and bloodglucose level through caudal vein in four weeks and six weeksrespectively. The animals were anesthetized with1%sodium pen-tobarbital intraperitoneally. To expose the pelvicganglions on both sides of rectum via a ventral midline incision,weconnected the RM6240multi-channel physiological signal acquisitionsystem with electric stimulation probe to measure the maximal penileintracavernous pressure/mean arterial blood pressure (ICPmax/map). Weadded the reaction reagent to each group after the carvernosum tissuewas evenly grinded. After reaction, the absorbance was determined atthe wavelength of670nm by elisa reader. Then we prepared NAHS atdifferent concentrations with standard curve method and took the penile specimens to determine the H2S concentration in tissue. The expressionof CBS and CSE were detected by immunohistochemical SP methodafter the carvernosum tissue was fixed with formaldehyde for12h. Thepenile tissue was ground to fine powder with liquid nitrogen. Then weadded cell lysis solution and extracted the protein, took the supernatantto detect the concentration of CBS and CSE in carvernosum tissue withwestern blotting method after the tissue fluid was centrifuged at therotation rate of12000/minute for5minutes at4degreeentigrade.Results: The serum concentrations of glucose were higher ingroup B（23.9±1.6mmol/l） and group D（22.5±3.6mmol/l） than groupA （5.7±0.3mmol/l）and group C（5.4±0.3mmol/l）(P＜0.05).The serumconcentrations of testosterone in all groups were no significantdifference(p＞0.05). After electrostimulation of5and7voltage, theICPmax/MAP in group A and C were significantly higher than group Band D respectively(P<0.05). The concentrations of H2S in plasma andpenile corpus cavernosum in group A and C were significantly higherthan group B and D respectively(P<0.05). The expressions of CBS andCSE in the penile corpus cavernosum, detected byimmunohistochemistry and western blot, were significantly higher ingroup A and C than in group B and D respectively(P<0.05). Theexpressions in group C was significantly higher than in group D(P<0.05).Conclusion: Hyperglycemia inhibits the erectile function of rats may be related to the decreasing of the concentration of serum H2S anddown-regulation of the expression of CBS and CSE in penile corpuscavernosum. |
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