sphingosine-1-phosphate and Erectile-Dysfunction

The population with diabetes mellitus-induced erectile dysfunction is increasing rapidly, but current drugs are not effective in treating erectile dysfunction. Studies of the traditional Chinese medicine extract berberine on diabetes and its complications provide us with new ideas.. To evaluate the therapeutic effect and potential mechanism of berberine on the erectile function of diabetic rats.. Fifty male Sprague-Dawley rats were randomly grouped, and 42 rats were injected intraperitoneally with streptozotocin to establish a diabetes model. Erectile dysfunction rats were screened out through the apomorphine test and randomly divided into the diabetes mellitus and berberine groups, and these animals were administered berberine (200 mg/kg/day) and normal saline by gavage for 4 weeks. Primary corpus cavernous smooth muscle cells from healthy rats were cultured and treated with berberine.. Fasting blood glucose in the diabetes mellitus group was significantly increased, while berberine showed no significant effect on glucose. Erectile function was obviously impaired in the diabetes mellitus group, and berberine administration partially rescued this impairment. The expression of sphingosine kinase 1, S1PR2, and sphingosine-1-phosphate in the diabetes mellitus group was increased. Berberine partially inhibited the expression of sphingosine kinase 1 and S1PR2, but the decrease in sphingosine-1-phosphate was not significant. Moreover, mitogen-activated protein kinase pathway factor expression was upregulated and eNOS activity was decreased in the diabetes mellitus group. Berberine treatment could partially reverse these alterations. Severe fibrosis and apoptosis were detected in diabetic rats, accompanied by higher expression of TGFβ1, collagen I/IV, Bax/Bcl-2, and caspase 3 than in the other groups. However, supplementation with berberine inhibited the expression of these proteins and attenuated fibrosis and apoptosis.. Berberine ameliorated erectile dysfunction in rats with diabetes mellitus, possibly by improving endothelial function and inhibiting apoptosis and fibrosis by suppressing the sphingosine kinase 1/sphingosine-1-phosphate/S1PR2 and mitogen-activated protein kinase pathways.

Topics: Animals; Apoptosis; Berberine; Diabetes Mellitus, Experimental; Erectile Dysfunction; Lysophospholipids; Male; MAP Kinase Signaling System; Phosphotransferases (Alcohol Group Acceptor); Rats; Signal Transduction; Sphingosine; Sphingosine-1-Phosphate Receptors; Streptozocin

Postprostatectomy erectile dysfunction (ED) is thought to be due primarily to injury to cavernous nerve (CN) during surgery. The molecular mechanisms leading to ED after CN injury are poorly understood.. We determined whether transforming growth factor-β(1) (TGF-β(1)), sphingosine-1-phosphate (S1P) and RhoA/Rho-kinase (ROCK) signaling pathways were involved in corporal fibrosis after bilateral CN injury in rats.. Forty-eight 10-week-old male Sprague-Dawley rats were equally divided into the following four groups: normal control group (C); sham surgery group (S); bilateral CN crush injury group (I); and bilateral CN transection group (T). Within each of the four groups, two subgroups were analyzed as a function of time (1 and 8 weeks postoperatively).. Penile tissue was processed for immunoblot (RhoA, ROCK1, phospho-myosin phosphatase target subunit [MYPT1]), reverse transcription-polymerase chain reaction (RT-PCR) (TGF-β(1), sphingosine kinase type 1 [SphK1], and S1P(2)), immunohistochemistry (alpha smooth muscle actin [α-SMA]), and Masson's trichrome staining.. At 1 and 8 weeks postoperatively, the I and T groups had a significantly decreased smooth muscle cell/collagen ratio, the expression of α-SMA and phospho-MYPT1 compared to the C group. Densitometry revealed a significantly higher expression of RhoA and ROCK1 in the T group compared to the C group at 1 and 8 weeks postoperatively. For the I group, the expression of RhoA significantly increased starting from 1 week postoperatively, but the expression of ROCK1 significantly increased as late as 8 weeks following injury. The expression of TGF-β(1) and S1P(2) mRNA in the I or T group remained significantly increased up to 8 weeks compared to the C group, despite significant reduction at 8 weeks compared to 1 week postoperatively. The expression of SphK1 mRNA in the I and T groups was significantly increased at 1 week but not 8 weeks postoperatively.. Our data suggest that S1P and RhoA/ROCK1 signaling may be involved in corporal fibrosis associated with loss of smooth muscle through coordination with TGF-β(1) after CN injury.

Topics: Animals; Blotting, Western; Erectile Dysfunction; Lysophospholipids; Male; Penis; Prostatectomy; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; rho-Associated Kinases; rhoA GTP-Binding Protein; Signal Transduction; Sphingosine