新型毒品氯胺酮通过MTDH/MAPK信号通路调控上皮-间质转化诱导膀胱纤维化的作用及机制

Ketamine is a novel type of drug, which has been illicitly abused in teenagers, and the number of recreational abusers has been increasing year by year. Ketamine induced uropathy is one of the important complications of ketamine abusing, and bladder fibrosis is a vital sign of the uropathy progression. Our primary results detected the deposition of collagen fibers in suburothelium in ketamine induced cystitis rats, and further research revealed that MTDH upregulation and epithelial-mesenchymal transition may be related to bladder fibrosis. However, the mechanism is unknown. Recent studies thought the MAPK signal pathway may be associated with bladder fibrosis in ketamine induced cystitis. We want to uncover the molecular mechanism of epithelial-mesenchymal transition regulated by MTDH/MAPK signal pathway in ketamine induced bladder fibrosis. In the process, we will make use of clinical specimens, animal model and cell model, some experiment techniques will also be used to reveal the hypothesis, including immunohistochemistry, immunofluorescence, qPCR, Western Blot and siRNA transfection. This research would provide a potential mechanism for ketamine induced bladder lesions progression and targeted therapy for this lesion.

氯胺酮作为一种新型毒品在青少年中滥用呈逐年增长的趋势，泌尿系病变是氯胺酮滥用的重要并发症之一，膀胱纤维化是病情进展的重要标志。申请者前期的研究发现氯胺酮相关性膀胱炎组织标本，存在间质中胶原纤维的广泛沉积，进一步研究发现膀胱纤维化可能与MTDH上调及上皮-间质转化有关，但具体机制不明。有研究发现MAPK信号通路可能参与了氯胺酮相关性泌尿系病变中膀胱纤维化。本项目拟通过临床标本、动物和细胞模型，结合免疫组化、免疫荧光、qPCR、Western Blot和siRNA转染等技术，阐明MTDH/MAPK信号通路调控上皮-间质转化在氯胺酮诱导膀胱纤维化的分子机制，为氯胺酮导致膀胱进行性病变的靶向药物治疗提供基础。