高迁移率族蛋白B-1在良性前列腺增生中的作用及信号通路研究

Tissue inflammation plays an important role in the pathogenesis of benign prostatic hyperplasia (BPH). Our previous studies have also found prostatic inflammation was existed in 47.7% of BPH cases, but inflammation-mediated pathogenesis of BPH is still unclear. High mobility group box 1 protein (HMGB1) is an important late inflammatory cytokine, which could induce proliferation and migration of smooth muscle cell, but whether it mediates tissue inflammation promoting development of BPH remains to be discussed. The expression and distribution of HMGB1 are detected from prostate tissue of patients with BPH and rat BPH model to confirm whether the HMGB1 is involved in the occurrence and development of BPH. The cultured prostate epithelial cells are stimulated by inflammatory factor, and the expression and content of HMGB1 in the cell and medium are measured in order to clarify that the prostate cells can generate endogenous HMGB1. Then, we use HMGB1 to stimulate the cultured smooth muscle cells to verify if HMGB1 may promote prostate smooth muscle cell proliferation and migration. Furthermore, using block strategy to reveal the signal transduction mechanisms of HMGB1 induced cell proliferation and migration. The above researches will help to reveal pathogenesis of tissue inflammation induced BPH and provide research strategy for treatment of lower urinary tract obstructive symptoms induced by BPH.

组织炎症在良性前列腺增生（BPH）的发病过程中起重要作用。我们的前期研究发现47.7% BPH患者伴有组织炎症，但组织炎症促BPH的发病机制尚不明确。高迁移率族蛋白B-1 (HMGB1) 是重要的晚期炎症因子，具有促组织平滑肌细胞增殖、迁移的能力，但其是否介导了组织炎症促BPH发生过程尚需探讨。本项目拟收集BPH患者前列腺组织标本、复制大鼠BPH动物模型，检测HMGB1的分布与表达，以证实HMGB1参与了BPH的发生、发展过程；以致炎因子刺激人前列腺上皮细胞，检测细胞与培养液中HMGB1的变化，阐明组织炎症可致前列腺细胞产生内源性HMGB1；采用HMGB1刺激人前列腺平滑肌细胞，证实其可促进前列腺平滑肌细胞增殖、迁移；运用阻断为主的策略明确HMGB1致前列腺平滑肌细胞增殖、迁移的信号转导机制。以上研究有助于完善组织炎症致BPH的发病机制，并为BPH引起的下尿路梗阻症状的治疗提供新思路。

良性前列腺增生(BPH)是引起中老年男性排尿障碍原因中最常见的一种疾病，主要临床表现为下尿路症状；其发病机制复杂，一直是泌尿外科研究领域的热点问题。近年来，越来越多的研究表明前列腺组织炎症在BPH的发病过程中起重要作用，但组织炎症致BPH发病机制和作用靶点仍待进一步明确。高迁移率族蛋白B-1 (HMGB1) 是重要的晚期炎症因子，由于其在炎症和组织修复中的独特作用，使其受到越来越多的关注，但HMGB1是否介导了组织炎症促BPH发生过程尚需探讨。本项目在前期研究的基础上扩大临床样本容量，通过体内、外实验完成以下工作：1.明确HMGB1与BPH患者前列腺体积等临床指标之间的关系；2. 确定HMGB1对雄激素诱导去势大鼠BPH的影响及可能机制；3. 阐明内源性HMGB1的产生及HMGB1促前列腺上皮、间质细胞增生、迁移的作用及其信号转导机制。通过本项目的实施有助于进一步阐明组织炎症致BPH的发病机制，为BPH介导的下尿路梗阻症状的治疗方案提供新思路，并为后续研究奠定基础。