| Background:Erectile dysfunction affects quality of life between patients and partners seriously. Curing ED is not only the need of patients, and has important social significance. Currently, it has been estimated that there exists more than100million patients all over the world. Diabetic ED is an important type of ED. Investigation shows that about50%of diabetic patients have ED, but the specific mechanism is unclear. Diabetes can cause systemic small blood vessels, including small penis artery, structural changes, such as endothelial injury, thickening of basement membrane, increasing blood viscosity, erythrocyte aggregation, platelet adhesion and aggregation, resulting in thrombosis and or micro-vascular occlusion, etc, which is the important reason for the tissue ischemia hypoxia. The molecular mechanism of penile erectile mainly in a variety of sexual stimulation under the action of corpus cavernosum non adrenergic nerve endings non cholinergic nerve (NENA) neurogenic nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) release. NO, which is generated by eNOS’s decomposition of L-arginine, can cross the cell membrane to stimulate cavernous smooth muscle cells’soluble granulate cyclic acid (sGC) to change guanosine triphosphate (GTP) into second messenger cGMP and then stimulate protein kinase I which is depended on cGMP(cGMP dependent protein kinase I, cGKI). The Ca2+concentration in CCSMC reduced and caused cavernous smooth muscle relaxation. In the process of erection, penile corpus cavernosum smooth muscle relaxation makes blood flow into penile cavernous gap and expands a lot. Penile swelling gave a pressure on tunica albuginea and on the vein of sious cavernosus and superficial dorsal veins of penis which limited the blood flowing from cavernosa and increased the blood vessel return resistance. So, venous blood cannot flow out and the blood pressure increased and produced strong erection. Many research showed that: IGF-1can improve the formation of new vessels and plays an important role in vascular damage repair, and at the same time it can promote cell proliferation, migration and inhibiting apoptosis and maintain the integrity of the cell. IGF-1also took part in NO/sGC/cGMP’s signaling conduction path which caused anapetia and improved erectile dysfunction. In IGF-1’s half-life period is short in blood circulation and mainly combined with IGFBP-3.IGFBP-3is not only the carrier protein of IGF-1but also prolongs the half-life of IGF-1, IGFBP-3carried most IGF-1. IGFBP-3can regulate IGF-1’s validity by competitive inhibition of the combination of IGF-1and IGF receptor (insulin like growth factor receptor, IGFR). High level expression of IGFBP-3can reduce the role of IGF-1in the corpus cavernous tissue.Objective:This topic mainly through the establishment of diabetic ED rats and Diabetes without ED the animal model of rats and normal rats, understand the DM group life habits and the change of erectile function in rats. Research corpus cavernous tissue in rat diabetic erectile dysfunction in the expression of IGFBP-3, observe its effect on penile erectile function, and then test the NO-cGMP pathway aspects, discusses IGFBP-3on the pathogenesis of diabetic erectile dysfunction, the role of process, develop new ED treatment for clinical provide basis of early research.Methods:Selecting30healthy male Wistar rats at2months of age, which have been tested by Apomorphine (APO) function and have normal erectile function, randomly divided into2groups:(1)normal control group:9rats, only to give regular diet;(2)diabetic model group:21rats, to give Intraperitoneal injection of60mg/kg STZ induced diabetic rats model, cutting the tail of the rat blood test random blood glucose levels after2weeks, to establish success criteria for diabetes animal model under a random blood glucose level>16.7mmol/L. After the successful establishment of diabetic rats about8weeks, the apomorphine APO function test will be used. The growth of penis body, glans hyperaemia, and peeping out of penile erection, the times of rats’penile erectile will be recorded within30minutes.1erection in30minutes is regarded normal and diabetes non-ED model group and ED model group will be screened. First we compare the diabetes group’s and normal control group’s weight and blood glucose before and after building models and then compare the normal control group, diabetes non-ED model group and the diabetes ED model group:rat penis intracavernous pressure (ICP)/Mean arterial pressure (MAP) and total ICP test, RT-PCR tests the expression of IGFBP-3mRNA, Western Blot tests expression of IGFBP-3protein, ELISA method detects the content of cGMP.Results:(1)Rats weight and blood glucose determination results of diabetes group and normal group before and after establishing models:normal control group rats’ weight increases with the increasing of the weeks; DM group rats’daily water consumption and urine were significantly increased, the weight has lost and the color of hair changed to dim compared with normal rats. The weight was significantly reduced (p<0.001), while the blood sugar level was significantly higher than the control group (p<0.001).(2) The apomorphine (APO) screening experiment results:9rats’penile erectile function was normal from normal group;11rats of19diabetic rats which are the models did not see the penis erection for diabetes ED group, and the rest8diabetic rats were visible penile erectile which can be regard as not ED of diabetes group.(3) The penis intracavernous pressure (ICP)/mean arterial pressure (MAP) and the total value of ICP in diabetes ED rat model group are lower than normal control group and diabetic non-ED group(P<0.01), and there is no significant statistical significance (P>0.05) between diabetes non-ED group and normal control group.(4) Rt-pcr to determine the expression of IGFBP-3mRNA results show:diabetic ED group of corpus cavernous IGFBP-3mRNA expression level was significantly higher than normal control group and diabetes non-ED group, diabetes non-ED group’s IGFBP-3mRNA expression level of was obviously higher than normal control group.(5)The expression of IGFBP-3protein which is detected by Western Blot showed:diabetes ED group’s the expression of IGFBP-3protein is significantly higher than normal control group and diabetes non-ED group, and diabetes non-ED group’s expression of IGFBP-3protein was obviously higher than normal control group.(6) The detection of the content of the cGMP by ELISA method showed:the content of diabetes ED group was significantly lower than normal control group and diabetes non-ED group (P< 0.01), and there is no significant statistical significance between diabetes non-ED group’s cGMP content and normal control group (P>0.05).Conclusion:Through this topic’s research, we may draw the following conclusions:1、 IGFBP-3’s expression level increases in the tissue of diabetic rat corpus cavernous;2、 IGFBP-3’s expression level increases significantly in corpus cavernous tissues of diabetic ED rats;3、 IGFBP-3mRNA and IGFBP-3protein1expression level and cGMP showed a negative relationship in diabetic ED rats of the corpus cavernous tissue;4、 diabetes can cause the increasing of IGFBP-3expression. When IGFBP-3’s expression quantity increases to a certain point, it will decrease the content of corpus cavernous tissue local cGMP, which may be one of the important causes of erectile dysfunction. |
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