| Background Male erectile dysfunction (ED) is a common andfrequently-occuring disease, about one hundred and fifty million men have beensuffered from ED.Epidemic surveys found that ED is one of the chroniccomplications of diabetes mellitus patients. With the improvement of life quality, theDM morbidity rate has been growing up. It is supposed that there will be two hundredand ten million men suffered from DM until 2010 in world, including about 20～40million in China. The complication of diabetes mellitus has a bad effect on health andalso can cause diseases of cardiovascular system, nephros and retina. ED is becominga focus because of its appearing earlier in the course of DM. In all patients of DM,about 50% are ED patients. The morbidity rate of ED is higher 2～5 times in DMpeople than in non-DM people. Normal sexual life has been concerned by more andmore people. The number of diabetes mellitus patients with ED will be growing upmore with age and course of disease. So researching on the pathogeny of DM withED can offer theory and guidance to clinic practice.Penile erection is a neurovascular event modulated by psychological factors andhormonal status. On sexual stimulation, nerve impulses cause the release ofneurotransmitters from the cavernous nerve terminals and of relaxing factors from theendothelial cells in the penis, resulting in the relaxation of smooth muscle in the arteries and arterioles supplying the erectile tissue and a severalfold increase in penileblood flow. Within the muscle, nitric oxide activates a soluble guanylate cyclase,which raises the intracellular concentration of cyclic guanosine monophosphate(GMP). Cyclic GMP in turn activates a specific protein kinase, which phosphorylatescertain proteins and ion channels, resulting in the opening of potassium channels andhyperpolarization of the muscle-cell membrane, sequestration of intracellular calciumby the endoplasmic reticulum, and blocking of calcium influx by the inhibition ofcalcium channels. The consequence is a drop in cytosolic calcium concentrations andrelaxation of the smooth muscle. During the return to the flaccid state, cyclic GMP ishydrolyzed to GMP by phosphodiesterase type 5. In vivo experiments, have shownthat inhibitors of NO synthase and cGMP formation prevent the erectile response topelvic nerve stimulation, suggesting that the NO-cGMP pathway acts as thepredominant mechanism of erectile neurotransmission.NO is generally considered to act as an important neuronal and non-neuronalmediator in the regulation of smooth muscle tone, blood flow and secretory function.NO is produced by NOS from L-arginine. Two constitutive isoforms of NOS exist,acting as regulators of physiological processes. The activities of these isoforms areregulated by a variety of humoral and neuronal mediators, such as vasoactiveintestinal poly-peptide (VIP) and acetylcholine. Neuronal NOS (nNOS) must bedierentiated from endothelial NOS (eNOS). NOS isoforms are located in endothelial,neuronal, epithelial and muscular structures. Preliminary studies demonstratednumerous nNOS-positive nerve fibers in the corpus cavernosum. Neuronal NOS hasbeen thought to be the essential origin of NO in the corpus cavernosum, while therelevance of eNOS remains unclear.DM can affect normal function of NO-cGMP pathway.The chemical property ofNO is not steady, and its half-life time is short. And it will become to nitrate or nitrite in five seconds after activating cGMP.So it is difficult to measure the content of NO.Now, the method of measuring is indirect, researching on NO is being concentrated inex vitro corpus cavernosum tissue. DM which results in decreasing activity of NOSmay cause the content of NO to decrease in corpus cavernosum.Objectives To investigate the ideal diabetic rats model with erectiledysfunction and pathogeny of the disease.Methods1 To establish ideal rats model of diabetes mellitus with erectile dysfunction(ED)through streptozotocin(STZ) injection: 24 male SD rats were randomly divided intofour groups(control group,STZ 40 mg/kg group,STZ 60 mg/kg group,Buffergroup),6 rats each group. And all rats were observed four days, one week, two weeksand three weeks after STZ injection. The mass, erectile frequency induced byapomorphine and fasting blood glucose should be recorded.2 To investigate the nNOS change in corpus cavernosum of diabetic rats modelwith erectile dysfunction: 40 rats were first divided into two groups randomly, 20 ratseach that were 4 week group and 7 week group. In the first experiment,diabetesmellitus rats model and with erectile dysfunction were made through streptozotocin(STZ) injection, according to the model standard, And then 4 week group and 7week group divided into four groups, that were control group(5 rats each, withoutSTZ injection), diabetes mellitus rats with erectile dysfunction group(DM&EDgroup), diabetes mellitus rats without erectile dysfunction group(DM group) andrats without diabetes mellitus and erectile dysfunction group after STZinjection(None group). Immunohistochemical staining method and color imageanalysis were used to observe expression of nNOS in rats corpus cavernosum ofdifferent group. Results1 To construct ideal model of diabetes mellitus with erectile dysfunction(ED) inrats through streptozotocin(STZ) injection: Significant difference exists in massamong groups of different test time and different dose of STZ injection (F=58.691, P=0.000 and F=17.888, P=0.000), There is no significant difference in erectilefrequency induced by apomorphine among groups of different test time and differentdose of STZ injection (F=1.427, P=0.244 and F=2.831, P=0.064), Significantdifference exists in fasting food glucose among groups of different test time anddifferent dose of STZ injection (F=16.314, P=0.000 and F=86.432, P=0.000).2 To investigate the nNOS change in corpus cavernosum of diabetic rats modelwith erectile dysfunction: There is significant difference in nNOS expression betweenDM&ED group and other three group (F=3.864, P=0.020),Expression of nNOS incorpus cavernosum in DM&ED group is the lowest in all four groups (P＜0.05). Nosignificant difference exists between 7 week group and 4 week group(F=0.012, P=0.913),and so does interaction(F=1.016, P=0.401). Another significant changeexists in the histopathology of corpus cavernosum, including penile nerve andultrastructure of smooth muscle cell.Conclusion1,The successful diabetic rats model with erectile dysfunction can be establishedby injecting STZ.2,The best dose of STZ injection to construct ideal diabetic rats model is 60mg/kg and the best time to choose ED rats model is about two weeks after STZinjection.3,In rats, diabetes mellitus can be considered if fasting serum glucose exceeds7.2 mmol/L, and erectile dysfunction can be considered if penile erection do notappear after APO injection. 4,The expression of nNOS has a descent tendency in diabetic rats with erectiledysfunction.5,In DM with ED rats, there was a degeneration in nerves of penis and smoothmuscle cell of corpus cavernosum. |
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