Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Mil Med Res. 2024 May 20;11(1):30. doi: 10.1186/s40779-024-00533-8.
Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH.
The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration.
P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH.
P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.
良性前列腺增生（BPH）是老年男性中最常见的疾病。越来越多的证据表明，牙周炎会增加 BPH 的风险，但具体机制尚不清楚。本研究旨在探讨关键牙周致病菌牙龈卟啉单胞菌（P. gingivalis）在 BPH 发展中的作用和机制。
提取并培养 BPH 合并牙周炎患者的龈下菌斑（Sp）和前列腺液（Pf）进行 16S rDNA 测序。建立结扎诱导牙周炎、睾丸酮诱导 BPH 及复合大鼠模型。将牙龈卟啉单胞菌及其毒性因子牙龈卟啉单胞菌脂多糖（P.g-LPS）注入大鼠前列腺腹叶，模拟其在前列腺中的定植。用 P.g-LPS 构建前列腺细胞感染模型，用于机制探讨。
BPH 合并牙周炎患者的 Pf 和 Sp 中同时检测到牙龈卟啉单胞菌、口腔链球菌、噬二氧化碳噬纤维菌等口腔病原体，且牙龈卟啉单胞菌的平均相对丰度最高。62.5%的患者 Pf 和 Sp 中均检测到牙龈卟啉单胞菌。同时发生牙周炎和 BPH 可协同加重前列腺组织学变化。牙龈卟啉单胞菌和 P.g-LPS 感染可引起前列腺上皮和基质明显增生（上皮厚度分别为对照组的 2.97-和 3.08 倍），胶原纤维纤维化增加（分别为对照组的 3.81-和 5.02 倍）。牙龈卟啉单胞菌感染促进前列腺细胞增殖，抑制细胞凋亡，并上调前列腺组织中炎症细胞因子白细胞介素 6（IL-6；为对照组的 4.47 倍）、白细胞介素 6 受体-α（IL-6Rα；为对照组的 5.74 倍）和糖蛋白 130（gp130；为对照组的 4.47 倍）的表达。P.g-LPS 可显著抑制细胞凋亡，促进细胞有丝分裂和增殖。P.g-LPS 通过 IL-6/IL-6Rα/gp130 复合物激活 Akt 通路，破坏前列腺细胞增殖与凋亡的失衡，诱发 BPH。
BPH 合并牙周炎患者 Pf 中牙龈卟啉单胞菌含量丰富。牙龈卟啉单胞菌感染可促进 BPH，可能通过炎症和 Akt 信号通路影响 BPH 的进展。
