【摘要】：目的：初步探討氯胺酮相關(guān)性泌尿系統(tǒng)損害的致病機(jī)制。 方法：25只雄性健康SD大鼠,體重250～300g,隨機(jī)分為5組,每組5只,分別為生理鹽水組(對照組)、氯胺酮10mg/kg實(shí)驗(yàn)組(K10組)、氯胺酮30mg/kg實(shí)驗(yàn)組(K30組)、氯胺酮60mg/kg實(shí)驗(yàn)組(K60組)和氯胺酮30mg/kg的停藥實(shí)驗(yàn)組(K30停藥組)。各組大鼠予以生理鹽水或不同劑量氯胺酮每天一次連續(xù)腹腔注射30天。觀察比較各組大鼠腹腔注射給藥后行為精神改變。于第30天給藥24h后,測量各組大鼠體重并同時取對照組、K10組、K30組和K60組大鼠腎、輸尿管和膀胱,K30停藥組大鼠于停藥2周后取腎、輸尿管和膀胱。從每組5只大鼠中隨機(jī)選擇一只大鼠,行腎、輸尿管和膀胱HE染色,比較各組大鼠腎、輸尿管和膀胱光鏡下病理差異。取每組余下4只大鼠膀胱行qRT-PCR檢測膀胱組織中H1R-mRNA的表達(dá)量,行統(tǒng)計(jì)學(xué)分析,進(jìn)行組間比較。 結(jié)果：(1)各組大鼠腹腔注射給藥前基線體重?zé)o統(tǒng)計(jì)學(xué)差異(P0.05)。腹腔注射給藥30天后,K10組、K30組、K60組和K30停藥組大鼠與對照組大鼠相比體重增長無統(tǒng)計(jì)學(xué)差異(P0.05)。 (2)對照組大鼠腎臟未見明顯異常改變,與對照組大鼠相比,K10組大鼠腎臟局灶未見明顯單核炎癥細(xì)胞浸潤,K30組、K60組和K30停藥組大鼠腎臟局灶可見單核炎癥細(xì)胞浸潤；各組大鼠輸尿管均未見明顯單核炎癥細(xì)胞浸潤；相較對照組,K10組、K30組、K60組和K30停藥組大鼠膀胱上皮層變薄,并見上皮下單核炎癥細(xì)胞浸潤。(3)對照組、K10組、K30組和K60組大鼠膀胱組織中H1R基因的mRNA表達(dá)情況有統(tǒng)計(jì)學(xué)差異(P0.05),K10組、K30組和K60組大鼠相較對照組可提高大鼠膀胱組織中H1R基因mRNA表達(dá)水平,且其表達(dá)水平呈劑量依賴性。K30停藥組較K30組大鼠膀胱組織中H1R基因mRNA表達(dá)水平下調(diào),差異有統(tǒng)計(jì)學(xué)意義(P0.05)。 結(jié)論：氯胺酮所致單核炎癥細(xì)胞浸潤(腎臟和膀胱)、膀胱上皮層變薄和組胺受體高表達(dá)(膀胱)等可能是氯胺酮相關(guān)性泌尿系統(tǒng)損害的重要致病機(jī)制；戒斷氯胺酮可能能有效治療氯胺酮相關(guān)性泌尿系統(tǒng)損害,逆轉(zhuǎn)疾病致病過程。圖21幅,表4個,參考文獻(xiàn)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.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R691.9

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