氯胺酮相关性泌尿系统损害致病机制的初步研究

发布时间：2018-11-27 11:48

【摘要】：目的：初步探讨氯胺酮相关性泌尿系统损害的致病机制。方法：25只雄性健康SD大鼠,体重250～300g,随机分为5组,每组5只,分别为生理盐水组(对照组)、氯胺酮10mg/kg实验组(K10组)、氯胺酮30mg/kg实验组(K30组)、氯胺酮60mg/kg实验组(K60组)和氯胺酮30mg/kg的停药实验组(K30停药组)。各组大鼠予以生理盐水或不同剂量氯胺酮每天一次连续腹腔注射30天。观察比较各组大鼠腹腔注射给药后行为精神改变。于第30天给药24h后,测量各组大鼠体重并同时取对照组、K10组、K30组和K60组大鼠肾、输尿管和膀胱,K30停药组大鼠于停药2周后取肾、输尿管和膀胱。从每组5只大鼠中随机选择一只大鼠,行肾、输尿管和膀胱HE染色,比较各组大鼠肾、输尿管和膀胱光镜下病理差异。取每组余下4只大鼠膀胱行qRT-PCR检测膀胱组织中H1R-mRNA的表达量,行统计学分析,进行组间比较。结果：(1)各组大鼠腹腔注射给药前基线体重无统计学差异(P0.05)。腹腔注射给药30天后,K10组、K30组、K60组和K30停药组大鼠与对照组大鼠相比体重增长无统计学差异(P0.05)。 (2)对照组大鼠肾脏未见明显异常改变,与对照组大鼠相比,K10组大鼠肾脏局灶未见明显单核炎症细胞浸润,K30组、K60组和K30停药组大鼠肾脏局灶可见单核炎症细胞浸润；各组大鼠输尿管均未见明显单核炎症细胞浸润；相较对照组,K10组、K30组、K60组和K30停药组大鼠膀胱上皮层变薄,并见上皮下单核炎症细胞浸润。(3)对照组、K10组、K30组和K60组大鼠膀胱组织中H1R基因的mRNA表达情况有统计学差异(P0.05),K10组、K30组和K60组大鼠相较对照组可提高大鼠膀胱组织中H1R基因mRNA表达水平,且其表达水平呈剂量依赖性。K30停药组较K30组大鼠膀胱组织中H1R基因mRNA表达水平下调,差异有统计学意义(P0.05)。结论：氯胺酮所致单核炎症细胞浸润(肾脏和膀胱)、膀胱上皮层变薄和组胺受体高表达(膀胱)等可能是氯胺酮相关性泌尿系统损害的重要致病机制；戒断氯胺酮可能能有效治疗氯胺酮相关性泌尿系统损害,逆转疾病致病过程。图21幅,表4个,参考文献51篇。
[Abstract]:Objective: to explore the pathogenetic mechanism of ketamine associated urinary system damage. Methods: Twenty-five healthy male SD rats, weighing 250g, were randomly divided into 5 groups: normal saline group (control group), ketamine 10mg/kg experimental group (K10) and ketamine 30mg/kg experimental group (K30). Ketamine 60mg/kg group (K60 group) and ketamine 30mg/kg withdrawal group (K30 group). Rats in each group were given normal saline or different doses of ketamine once a day for 30 days. The changes of behavior and spirit after intraperitoneal injection were observed and compared in each group. 24 hours after administration on the 30th day, the weight of the rats in each group was measured and the kidney, ureter and bladder of the control group, K10 group, K30 group and K60 group were taken out at the same time. The kidney, ureter and bladder of the rats in the K30 withdrawal group were removed 2 weeks after the withdrawal. One rat in each group was randomly selected for renal, ureteral and bladder HE staining. The pathological changes of kidney, ureter and bladder in each group were compared. QRT-PCR was used to detect the expression of H1R-mRNA in the bladder tissues of the remaining 4 rats in each group. Results: (1) there was no significant difference in baseline body weight before intraperitoneal injection (P0.05). After 30 days of intraperitoneal injection, there was no significant difference in weight gain between K10 group, K30 group, K60 group and K30 withdrawal group compared with control group (P0.05). (2) there were no obvious abnormal changes in the kidney of the control group. Compared with the control group, there was no significant mononuclear inflammatory cell infiltration in the renal foci of the K10 group, and mononuclear inflammatory cell infiltration was found in the renal focus of the K30 group, K60 group and K30 withdrawal group. No significant mononuclear inflammatory cell infiltration was found in the ureter of rats in each group. Compared with the control group, K10 group, K30 group, K60 group and K30 withdrawal group, the bladder epithelium thinned and the inflammatory cells infiltrated into the bladder. (3) the control group, K10 group, The mRNA expression of H1 R gene in bladder tissue of K30 group and K60 group was significantly different (P0.05). Compared with the control group, K10 group, K30 group and K60 group could increase the expression of H1 R mRNA in bladder tissue of rats. Compared with K30 group, H1 R gene mRNA expression was down-regulated in K30 group (P0.05). Conclusion: Ketamine induced mononuclear inflammatory cell infiltration (kidney and bladder), thinning of bladder epithelium and high expression of histamine receptor (bladder) may be the important pathogenetic mechanism of ketamine associated urinary system damage. Withdrawal of ketamine may be effective in the treatment of ketamine-associated urinary system damage and reverse the pathogenesis of the disease. There are 21 figures, 4 tables and 51 references.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R691.9

【参考文献】