Objective: To investigate the improving effect of S1P3 silencing on the erectile function of spontaneous hypertension rats (SHR).
Methods: Five 12-week-old healthy male WKY rats were included in group A and another 15 12-week-old healthy male SHRs equally randomized into groups B1 (intracavernously injected with 20 μl S1P3 siRNA lentiviral vectors ［2 ×108TU/ml］), B2 (intracavernously injected with 20 μl GFP lentiviral vectors ［2 ×108TU/ml］), and C (control). At 1 week after transfection, the ratio of the maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP) of the rats was measured, and the expressions of S1P3, ROCK1, ROCK2 and eNOS in the corpus cavernosal tissue were determined by immunohistochemistry, Western blot and RT-qPCR.
Results: There were no statistically significant differences in the body weight and serum T level among the three groups of rats. Under 0 V, 3 V and 5 V electrical stimulation, the ratios of ICPmax/MAP were 0.16 ± 0.01, 0.55 ± 0.03 and 0.82 ± 0.02 in group A, 0.15 ± 0.01, 0.55 ± 0.01 and 0.79 ± 0.03 in group B1, 0.10 ± 0.00, 0.22 ± 0.01 and 0.43 ± 0.01 in group B2, and 0.11 ± 0.01, 0.22 ± 0.01 and 0.42 ± 0.02 in group C, significantly lower in the latter two than in the former two groups (P < 0.05). The protein expressions of S1P3, ROCK1 and ROCK2 in the corpus cavernosum were remarkably down-regulated while that of eNOS up-regulated in groups A and B1 compared with those in groups B2 and C (P < 0.05). Groups A and B1, in comparison with B2 and C, also showed markedly decreased mRNA expressions of S1P3 (0.72 ± 0.04 and 0.71 ± 0.07 vs 1.00 ± 0.06 and 1.00 ± 0.10, P < 0.05), ROCK1 (0.99 ± 0.05 and 1.08 ± 0.16 vs 1.85 ± 0.44 and 2.02 ± 0.38, P < 0.05) and ROCK2 (1.00 ± 0.03 and 1.08 ± 0.16 vs 2.16 ± 0.78 and 2.46 ± 0.69, P < 0.05), but increased eNOS (1.04 ± 0.15 and 0.81 ± 0.23 vs 0.32 ± 0.08 and 0.32 ± 0.04, P < 0.05).
Conclusions: S1P3 siRNA can improve the erectile function of SHRs by inhibiting the expression of the S1P3 gene and down-regulating the RhoA/Rho kinase signaling pathway in the corpus cavernosum.
Keywords: RNA interference; corpus cavernosum; sphingosine-1-phosphate receptor 3; spontaneous hypertension rat.