Botulinum Toxin Type A In The Treatment Of Benign Prostatic Hyperplasia: An Experimental Study In Rats

Part1 The establishment and evaluation of benign prostatic hyperplasia model of ratObjective:to establish a reliable and easy model of benign prostatic hyperplasia of Sprague Dawley rat, which is the basis of the further study. Method: 4mg/kg/d testosterone propionate subcutaneous injection in post-emasculation mice has been used to build the benign prostatic hyperplasia model of SD rats. We compared the wet weight and size of the prostate in different modeling time, and used HE staining to observe the epithelial cells and stromal cells to understand the best cycle time of the model and the reliability of the model. Result:4mg/kg/d testosterone propionate subcutaneous injection can conspicuously increase the wet weight and the size of the model prostate. The best cycle time of the model is 21days.HE staining indicates the epithelial cells and stromal cells proliferation was visible. Conclusion:We can use 4mg/kg/d testosterone propionate subcutaneous injection for 21 days to build the benign prostatic hyperplasia model of SD rats. This model is reliable and easy to manipulate. Part 2Study on different doses of botulinum toxin type-A injection in the prostate of BPH ratObjective:to explore the changes before and after different doses of botulinum toxin type A injection in the prostate of BPH SD rat, and observe the apoptosis in the prostate. Method:Different doses of botulinum toxin type-A were injected into the prostate of the BPH rat model. One week later we harvested the prostate, got its wet weight and volume and used TUNEL to observe the apoptosis in the prostate. Result:One week after different doses of botulinum toxin type-A injection, the wet weight and volume of the prostate had decreased sharply. The wet weight has decreased from 1.473±0.087g in control group to 0.386±0.046g in the 20U BOTOX injection group(P<0.01). The volume has decreased from 1.16±0.07ml in control group to 0.262±0.035ml in 20U BOTOX injection group(P<0.01).The TUNEL staining indicate that the botulinum toxin type-A can lead cell apoptosis in the prostate of the rat model. The apoptosis index of the 20U group was 0.711±0.154, compared to 0.035±0.014 in the control group. Conclusion: Botulinum toxin type-A injection can activate the cell apoptosis of the benign prostatic hyperplasia, which leads to the decrease of the prostate wet weight and volume. Part 3Study on the mechanism of botulinum toxin type-A for the treatment of benign prostatic hyperplasiaObjective:to explore the mechanism of the botulinum toxin type-A to activate the apoptosis of benign prostatic hyperplasia. Method:10U botulinum toxin type A was injected to the prostate of the benign prostatic hyperplasia rat model and one week later the prostate were harvested. We used immunohistochemistry to study the apoptosis-related protein expression in the prostate. Result:After botulinum toxin type-A injection in the prostate, the expression of Bcl-2 was decreased compared with the control group and the expression of Fas and Caspase-3 were increased. Conclusion:botulinum toxin type-A can inhibit the expression of Bcl-2 and promote the expression of Fas and Caspase-3 to activate the apoptosis of the prostate cells, which leads to decrease of the prostate wet weight and volume.