Hata Junya, Matsuoka Kanako, Harigane Yuki, Yaginuma Kei, Akaihata Hidenori, Meguro Satoru, Honda-Takinami Ruriko, Onagi Akifumi, Sato Yuichi, Ogawa Soichiro, Uemura Motohide, Kojima Yoshiyuki
Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan.
Int J Urol. 2024 Dec;31(12):1429-1437. doi: 10.1111/iju.15576. Epub 2024 Sep 11.
The expressions of complement component C5a and NLRP3 inflammasome and the antiproliferative effect of resveratrol in benign prostatic hyperplasia (BPH) model rat were analyzed to clarify the BPH proliferative mechanism.
This study used the pathological stromal-dominant BPH model rat by urogenital sinus implantation (UGS). Expression of C5a, NLRP3, Caspase-1, IL-1β, and IL-18 using rat BPH tissues at 2, 3, and 8 weeks (n = 6, respectively) after UGS implantation were analyzed by qRT-PCR, western blotting analysis, and immunohistochemical (IHC) analysis. Serum IL-1β levels in BPH model and sham rats were measured by enzyme-linked immunosorbent assay. Furthermore, resveratrol, as the NLRP3 pathway inhibitor, was administered to BPH model rat to assess the antiproliferative effect on the BPH proliferative process. The proliferative effect on prostate was evaluated by Ki-67 protein expression.
The expression levels of C5a, NLRP3, Caspase-1, IL-1β, and IL-18 in qRT-PCR, western blotting, and IHC were significantly upregulated in BPH tissues compared to control prostate tissues and showed increases with time (all p < 0.05). Serum IL-1β levels in BPH model rats had significantly increased compared to sham rats. On IHC, deposition of C5a, NLRP3, Caspase-1, IL-1β, and IL-18 was abundant in stromal areas of BPH. The administration of resveratrol significantly decreased prostate weight and expressions of NLRP3, IL-1β, IL-18, and Ki-67 (all p < 0.05).
NLRP3 inflammasome activation by complement C5a produces IL-1β and IL-18 through Caspase-1 during the BPH proliferative process. NLRP3 inflammasome have the possibilities to be a therapeutic target for BPH proliferation by inhibiting the NLRP3 inflammasome pathway.
分析补体成分C5a和NLRP3炎性小体的表达以及白藜芦醇对良性前列腺增生（BPH）模型大鼠的抗增殖作用，以阐明BPH的增殖机制。
本研究采用经尿道生殖窦植入（UGS）建立的以病理基质为主的BPH模型大鼠。通过qRT-PCR、蛋白质免疫印迹分析和免疫组织化学（IHC）分析，检测UGS植入后2、3和8周（每组n = 6）大鼠BPH组织中C5a、NLRP3、半胱天冬酶-1、白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18）的表达。采用酶联免疫吸附测定法检测BPH模型大鼠和假手术大鼠血清IL-1β水平。此外，将白藜芦醇作为NLRP3途径抑制剂给予BPH模型大鼠，以评估其对BPH增殖过程的抗增殖作用。通过Ki-67蛋白表达评估对前列腺的增殖作用。
与对照前列腺组织相比，BPH组织中qRT-PCR、蛋白质免疫印迹和IHC检测的C5a、NLRP3、半胱天冬酶-1、IL-1β和IL-18表达水平显著上调，且随时间增加（均p < 0.05）。BPH模型大鼠血清IL-1β水平较假手术大鼠显著升高。在免疫组织化学检测中，BPH基质区域C5a、NLRP3、半胱天冬酶-1、IL-1β和IL-18沉积丰富。给予白藜芦醇可显著降低前列腺重量以及NLRP3、IL-1β、IL-18和Ki-67的表达（均p < 0.05）。
在BPH增殖过程中，补体C5a激活NLRP3炎性小体，通过半胱天冬酶-1产生IL-1β和IL-18。抑制NLRP3炎性小体途径，NLRP3炎性小体有可能成为BPH增殖的治疗靶点。
