下尿路症状（LUTS）发病率逐年升高，其中因前列腺增生症梗阻膀胱出口后导致的膀胱过度活动症是最困扰患者的症状。目前临床多采用M受体阻滞剂或β3受体激动剂治疗，但效果有限且存在尿潴留风险。我们前期研究发现：TGF-β1在膀胱出口梗阻致膀胱过度活动的雄性大鼠尿液中表达升高，并可以增强膀胱平滑肌的收缩，而抑制LIM激酶（LIMK）表达或活性后可以显著削弱TGF-β1的促收缩效应；此外，LIMK介导的丝切蛋白(cofilin)磷酸化是控制平滑肌收缩关键信号分子。因此，我们推测TGF-β1可能通过促进LIMK介导的丝切蛋白磷酸化，从而增强膀胱平滑肌收缩并促进了膀胱出口梗阻后膀胱过度活动症的发生发展。本项目拟从细胞、组织及动物三个层面探究并进一步验证LIMK在TGF-β1诱导的膀胱出口梗阻致膀胱过度活动中的关键作用，并为研究以LIMK为靶点的LUTS药物治疗提供理论依据。

An increasing number of patients are suffering from lower urinary tract symptoms (LUTS) in recent years, among which, overactive bladder (OAB) suggestive of bladder outlet obstruction (BOO) induced by benign prostate hyperplasia is the most bothersome symptom for these patients. The current strategies, muscarinic receptor antagonist, or β3 receptor agonist, however, show low efficacy, and may increase the risk of acute urinary retention. In our preliminary investigation, increased expression level of TGF--β1 was detected in urine from rat with OAB suggestive of BOO, increased contractions of both smooth muscle tissue and smooth muscle cells induced by TGF--β1 were also detected in vitro, which may involve in LIM kinases (LIMK), theses contractile effects of TGF--β1 can be inhibited by LIMK inhibitors, which indicates that TGF--β1 may enhance the smooth muscle contraction by mediating LIMK. Additional evidence also demonstrates, that LIMK inhibitors show inhibiting effect on smooth muscle contraction by decreasing the level of phospho-cofilin in vitro. Therefore, it is hypothesized that TGF--β1 may involve in the development of OAB suggestive of BOO by inducing increased expression levels of LIMK and the subsequent increased phospho-cofilin level. The present project aims to explore this possible mechanism, meanwhile, this project will verify the key role of LIMK in bladder smooth muscle contraction, and therefore, to provide the evidence that LIMK may be a potential new pharmacological target for the treatment of LUTS.