Effects Of Icariin On Corpus Cavernosum Penis In Diabetes Mellitus Rats

Background:Metabolism of S-nitrosoglutathione (GSNO), a major biologicallyactive nitric oxide (NO) species, is catalyzed by the evolutionally conservedGSNO reductase (GSNOR). Formaldehyde dehydrogenase, formally ClassIII alcohol dehydrogenase (ADH3)[8,10], has recently been discovered topartially regulate nitrosothiol homeostasis by catalyzing the reduction of theendogenous nitrosylating agent S-nitrosoglutathione (GSNO)[8]. GSNORhas received considerable attention in the biomedical literature where it isoften referred to as GSNO reductase (GSNOR). Several studies haveimplicated this enzyme, and in particular GSNO reduction, as playing animportant role in conditions such as asthma, cardiovascular disease, andimmune function. Limin Liu[3]generated mice with a targeted gene deletionof GSNOR, and show that they exhibit substantial increases in whole-cellS-nitrosylation, tissuedamage, and mortality following endotoxic orbacterial challenge. GSNOR affords protection against nitrosative stressand influences vascular tone in a way that is evocative of SOD protectionagainst oxidative stress and regulation of blood pressure Oxidative stress and mitochondrial dysfunction are common features inpatients with diabetes[9]. Within mitochondria, superoxide is converted intohydrogen peroxide by MnSOD (manganese-containing superoxidedismutase), which is then detoxified by either the mGSH (mitochondrialglutathione) system, which uses the enzymes TRX-2R (thioredoxinreductase-2) and TRX-2[11]. Several studies have shown that the TRX-2system appears to have a more important role in preventing mitochondrialdysfunction[12]. GSNOR and thioredoxin enzyme systems participate incellular defence against nitrosative stress[10].Erectile dysfunction (ED) is now known as a treatable disorder and animportant risk-marker for diabetes. Cavernosal tissues from men witherectile dysfunction have been demonstrated to exhibit reduced lacunarspaces, reduced smooth muscle content, and a concomitant increase inconnective tissue deposition. Indeed, changes in penile tissue structuralintegrity is thought to contribute to venoocclusive dysfunction[13].Icariin，amajor active component isolated from plantsin the Epimedium family，hasbeen previously confirmed to improve cardiovascular function[6], inducetumor cell differentiation and increase bone formation, improvereproductive functions like sex hormone[13]. Recently, studies have showthat Icariin increases the erectile function and restores the eNOS expressionin rats.This study investigated the effect of Icariin (ICA) supplementation to corpora cavernosum in a streptozotocin-induced diabetic rat model system.Key mediators oxidoreductase TrxR2and GSNOR were investigated.Objective:To detection the expression of GSNOR and TRX-2R instreptozotocin-induced diabetic rats model system with Icariin (ICA)supplementation.Methods:1．Forty sprague dawley rats were randomly distributed into a controlgroup and four streptozotocin-induced diabetes groups. Diabetic ratswere randomly divided into four groups; the frist group received salineas a placebo for3weeks by oral gavage; the second group receivedICA30mg/kg/day for3weeks by oral gavage; the third groupreceived ICA70mg/kg/day for3weeks by oral gavage;the fourthgroup received ICA100mg/kg/day for3weeks by oral gavage. Weobserved the effects of ICA from both diabetic and normal animals.The blood of the heart were tested for testosterone and estradiol.2． TEM and light microscope were used to observe the corporacavernosum of penis.3．Immuno-histochemical technique was used to locate the expressionof GSNOR and TrxR2in penis.4．Western blot was used for detecting the expression of GSNOR andTrxR2in penis. 5．TUNEL were used for testing the apoptosis in penis.Results:1. Significant difference exists in fasting food glucose among groupsbetween the control group and the mid dose group(p=0.002).Significant differences exists in testosterone and estradiol amongcontrol group and mid dose group(p<0.05).2. Numerous pathological changes (decreased smooth muscle cells,fibroblasts increased and a concomitant increase in connective tissue)were noted in the corpora cavernosum of penis of diabetic rats; thesechanges were attenuated in diabetic animals that received ICA. ICAenhanced corpora cavernosum of penis growth in diabetic rats indifferent dosages.3. Immunohistochemistry showed that there were GSNOR proteinexpressions in the cytoplasm of the rat’s dorsal nerve cell of penis andcavernous sinus smooth muscle cell.TrxR2protein high expressions incavernous sinus smooth muscle cell. Both of them enhancedsignificantly with the rising of the concentrations of ICA.4. Western Blot result showed the expression of GSNOR and TrxR2protein in groups received ICA were higher than that of non-ICA rats,reached a maximum level in the group received ICA100mg/kg/day.5. TUNEL result showed that the numbers of apoptotic cells werereduced by ICA. Experiment results showed significant differences in apoptosis rate among control group and mid dose group (p=0.002)，aswell as high dose group(p<0.05).Conclusion: These findings suggest that GSNOR and TrxR2might playan important role in the active ffect of Icariin (ICA) supplementation tocorpora cavernosum in a diabetic rats.