NLRP3炎性小体与小鼠间质性膀胱炎的相关性研究

The role of NLRP3 inflammasome in cyclophosphamide-induced cystitis of rat

目的通过建立小鼠间质性膀胱炎(IC)模型,探讨Nod样受体蛋白3(NLRP3)炎性体在IC中的作用和机制,进而为IC的治疗寻求新靶点。方法 C57BL/6J小鼠40只,随机分成4组:空白对照组(生理盐水注射)10只,IC模型组(腹腔注射环磷酰胺,150mg/kg,24h后观察各项指标)10只,BHB对照组(每12h注射NLRP3炎性小体抑制剂BHB,125mg/kg,3次,第3次注射BHB2h后腹腔注射环磷酰胺150mg/kg)10只,IC治疗组(IC+NLRP3抑制剂处理)10只。HE染色观察病理学特征,RT-PCR和Western blot检测间质性膀胱炎小鼠膀胱中NLRP3,caspase-1和IL-1β表达及其激活情况。结果环磷酰胺注射诱导NLRP3,caspase-1和IL-1β表达增加和活化。间质性膀胱炎小鼠膀胱体积增大、充血水肿,膀胱湿重显著增加,粘膜层细胞破坏,粘膜下层明显增厚,炎症细胞浸润增多,而BHB预处理的小鼠上述情况明显好转。结论 NLRP3炎症小体与间质性膀胱炎密切相关,可能为IC临床治疗的重要干预靶点。

Objective To investigate the role of Nod-like receptors 3（NLRP3） inflammasome in the development of interstitial cystitis（IC） and explore new targets for IC. Methods The 40 C57BL/6J mice were divided averagely into four groups： blank control group（normal saline）, IC model（treated with cyclophosphamide, CYP, 150 mg/kg, ip）, Sham control（intraperotoneally injected with BHB, 125 mg/kg, for 3 times at 12 h interval）, BHB＋IC group（intraperitoneally injected with 125 mg/kg of BHB and 150 mg/kg of CYP）. The bladder morphology was observed by HE staining and the expression of NLRP3 was determined by RT-PCR and Western blot. Results The intraperitoneal injection of CYP resulted in bladder hemorrhages, congestion and edema, the upregulation of NLRP3, caspase-1 and IL-1β expression levels in bladder. Inhibition of NLRP3 with BHB greatly attenuated the bladder congestion and edema, and downregulated the expression levels of NLRP3, caspase-1 and IL-1β in bladder. Conclusion NLRP3 inflammasome was closely associated with IC and might be a novel target for the treatment of IC.