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目的:研究紧密连接及紧密连接蛋白ZO-1在氯胺酮相关性膀胱炎中的改变及其意义。方法:60只6-8周龄的C57小鼠随机分为氯胺酮组和对照组,2组分别按时间梯度再分为4、8、12周组,每组各10只。氯胺酮组给予氯胺酮100mg/(kg·d)腹腔注射,对照组给予等量的生理盐水腹腔注射;电镜观察膀胱组织超微结构,免疫组化分析ZO-1蛋白表达。结果:氯胺酮组4周时出现指状突起减少,细胞电子密度减低,斑点状结晶减少,紧密连接疏松。8周时细胞管腔面变平,指状突起消失,紧密连接间距离进一步增大。12周时,除上述变化外,紧密连接几乎破坏,黏膜层出现断裂,黏膜下纤维化明显。氯胺酮组从4周开始,ZO-1蛋白表达于细胞质中,部分呈斑块状表达,细胞膜中表达极少,部分标本未见表达。对照组4,8,12周异常表达所占比例分别为0/10,1/10,1/10;实验组分别为7/10,7/10,9/10;Fisher确切检验后P值分别为0.003,0.02,0.001。结论:紧密连接破坏及ZO-1蛋白的异常表达与氯胺酮导致的膀胱炎相关,尿路屏障的破坏可能导致了氯胺酮相关性膀胱炎。
OBJECTIVE: To study the significance of tight junction and tight junction protein ZO-1 in ketamine-associated cystitis. Methods: Sixty-six C57 mice aged 6-8 weeks were randomly divided into ketamine group and control group. The two groups were divided into 4, 8 and 12 week groups by time gradient, 10 in each group. The ketamine group was given ketamine 100mg / (kg · d) intraperitoneally, while the control group was given the same amount of saline intraperitoneal injection. The ultrastructure of bladder tissue was observed by electron microscope and the expression of ZO-1 protein was analyzed by immunohistochemistry. Results: In the ketamine group, the number of finger protrusions decreased, the electron density of cells decreased, the speckled crystals decreased and the tight connections became loose. At week 8, the lumen of the cells became flattened, the finger-shaped protrusions disappeared and the distance between the tight junctions increased further. At week 12, in addition to the above changes, the tight junctions were nearly destroyed, the mucosal layers were broken, and submucosal fibrosis was evident. Ketamine group starting from 4 weeks, ZO-1 protein expression in the cytoplasm, some were plaque-like expression in the cell membrane expression is very small, some specimens were not expressed. The proportion of abnormal expression in the control group at 4, 8 and 12 weeks was 0/10, 1/10 and 1/10, respectively. The experimental groups were 7/10, 10/7 and 9/10, respectively. The P values after Fisher exact test were respectively Is 0.003, 0.02, 0.001. Conclusions: Tight junctions and the abnormal expression of ZO-1 protein are associated with ketamine-induced cystitis. The destruction of the urinary barrier may lead to ketamine-associated cystitis.