Daryanto Besut, Purnomo Athaya Febriantyo, Patriawan Yulian Salis, Purnomo Basuki Bambang
Department of Urology, Faculty of Medicine Universitas Brawijaya, Saiful Anwar General Hospital, Malang Indonesia.
Med Arch. 2023;77(6):446-450. doi: 10.5455/medarh.2023.77.446-450.
The α-adrenergic receptor antagonist is the most effective medical therapy to reduce the dynamic component in patients with BPH. However, long-term administration of receptor antagonists can cause upregulation of mRNA receptor expression, resulting in tolerance of drug effectiveness. PKC-α is involved in the process of prostate smooth muscle contraction through activation of the voltage-gated Ca2+ conducted canal, influenced by androgen hormones, especially testosterone, and has an isoform with Twist1, a transcription factor that plays a role in up-regulation of androgen receptors.
The aim of the study was to compare the effect of long-term tamsulosin monotherapy and tamsulosin - dutasteride combination therapy in PKC-α enzyme expression in prostate stromal tissue of Rattus norvegicus rats of Wistar strain.
Out of 80 samples of Rattus norvegicus rats were divided into 8 groups with different interventions: negative control group, positive control group, tamsulosin monotherapy administration for 1 day, 3 day, and 6 day groups, and tamsulosin - dutasteride combination therapy for 1 day, 3 day, and 6 day groups. BPH was induced with 3 mg/kg of testosterone proprionate for 3 weeks, continued with drugs administration according to intervention grouping. Prostate stromal tissue was taken and prepared for PKC-α enzyme measurement with ELISA method.
There was a significant difference (p<0.05) in the effect of tamsulosin monotherapy and tamsulosin-dutasteride combination therapy on the PKC-α expression. There was a strong positive relationship between the duration of tamsulosin-dutasteride combination therapy on the PKC-α expression, which means the longer the duration of the combination of tamsulosin-dutasteride combination the higher the PKC-α expression.
Administration of long-term tamsulosin - dutasteride combination therapy causes upregulation PKC-α expression more than tamsulosin only.
α-肾上腺素能受体拮抗剂是降低前列腺增生（BPH）患者动态成分最有效的药物治疗方法。然而，长期服用受体拮抗剂会导致mRNA受体表达上调，从而产生药物疗效耐受性。蛋白激酶C-α（PKC-α）通过激活电压门控Ca2+传导通道参与前列腺平滑肌收缩过程，受雄激素激素，尤其是睾酮的影响，并且具有与Twist1的同工型，Twist1是一种在雄激素受体上调中起作用的转录因子。
本研究旨在比较长期坦索罗辛单药治疗和坦索罗辛-度他雄胺联合治疗对Wistar品系大鼠前列腺基质组织中PKC-α酶表达的影响。
将80只大鼠样本分为8组，进行不同干预：阴性对照组、阳性对照组、坦索罗辛单药治疗1天、3天和6天组，以及坦索罗辛-度他雄胺联合治疗1天、3天和6天组。用3mg/kg丙酸睾酮诱导BPH 3周，然后根据干预分组继续给药。取前列腺基质组织，用酶联免疫吸附测定（ELISA）法制备用于PKC-α酶测量的样本。
坦索罗辛单药治疗和坦索罗辛-度他雄胺联合治疗对PKC-α表达的影响存在显著差异（p<0.05）。坦索罗辛-度他雄胺联合治疗持续时间与PKC-α表达之间存在强正相关，这意味着坦索罗辛-度他雄胺联合治疗持续时间越长，PKC-α表达越高。
长期给予坦索罗辛-度他雄胺联合治疗比仅给予坦索罗辛更能导致PKC-α表达上调。
