Objective To investigate the expression and clinical significance of H1 receptor in kidney and bladder tissue of rats after long term ketamine intraperitoneal injection.Methods This study was conducted from May 2012 to December 2012.Sixty male 2-month-old SD rats,weighted (200±10) g,were randomly divided into Group A and Group B.Each group concluded 30 rats.In the Group A,Ketamine (100 mg/kg) was given as intraperitoneal injection every other day,while normal saline (100 mg/kg) was given in Group B.The dosage was adjusted every week according to the weight of rats.After 2,4 and 6 months,10 rats from each group were randomly chosen.First,the micturition number during 2 h was recorded.Then,urine samples over a 24 h period were collected and the content of Na+ and K+ were determined.Finally,the blood samples were obtained from the apex of heart for the creatinine determination.The kidneys and bladders were harvested after the rats were sacrificed.HE staining was conducted on all the tissues.Immunohistochemical S-P method was used to detect the expression of H1 receptor in the bladder and kidney tissues from Group A and Group B.The average optical density (A Value) in each group was separately calculated by Imagepro-plus 6.0 software.All the parameters,mentioned above,were carefully compared.Results The successive rate of establishing rats model was 90％ (9/10),according to the pathological result after 6 months injection.The urine volume of 24 h in group A and B were (15.9±1.3) and (10.1±0.8) ml,respectively.Micturition frequency during 2 hours in group A and B were (6.9±1.4) and (3.0±0.5) times.The urine volume of 24 h and micturition frequency during 2 hours were significantly increased in group A (P＜ 0.05).The urine sodium within 24 h in group A was (1.7±0.1) mmol,which is increased significantly than that in group B (1.0±0.1 mmol).While the urine potassium was less in group A (1.1±0.1 mmol/d) than in group B (2.6±0.1 mmol/d) (P＜0.05).But the serum creatinine level were (60.5±6.8) and (58.1± 3.9) μmol/L in group A and B,which had no difference between the two groups (P＜0.05).The expression of H1 receptor in kidneys and bladder in group A was significantly raised compared with group B (P＜0.05).In the group A,the expression of H1 receptor level in kidney was 0.008±0.001,0.016±0.001,0.023±0.004 after 2,4 and 6 months drug used.The expression level in group A were significantly difference than that in group B (0.003±0.001,0.004±0.002,0.003±0.001) (P＜0.05) and goes up with prolonging the drug using.While in the bladder tissue,the level of H1 receptor expression was 0.017±0.006,0.031±0.012,0.036±0.007 in group A and 0.015±0.007,0.016±0.005,0.016±0.004 in group B,which could be noticed a significantly increasing in group A (P＜0.05).In 4 and 6 months,the H1 receptor expression level significantly raised than that in 2 months (P＜0.05).Conclusions Long term ketamine addiction exerts toxicity not only on the bladder but also on the kidney.The increased expression of H1 receptor in rats' kidney and bladder tissues of group A indicates that H1 receptor may be related to the ketamine-associated urinary system dysfunction.The urine sodium and potassium within 24 h may be a sensitive index for the assessment of degree of kidney damage in the early stage of ketamine-induced dysfunction than serum creatinine.

Objective To investigate the expression and clinical significance of four histamine receptors:H1R, H2R, H3R and H4R in urinary bladder of patients with ketamine-induced cystitis. Methods Immunohistochemical S-P method was used to detect the expression levels of histamine receptors:H1R, H2R, H3R and H4R in bladder tissues of 10 patients with ketamine-induced cystitis (experimental group) and distal tissue away from bladder tumors of 10 patients with cystectomy (control group). The average optical density (OD) values of four kinds of different histamine receptors were separately calcu-lated by Imagepro-plus 6.0 in two groups. At the same time, mast cells were marked by toluidine blue special dyeing and were counted. Results Comparing with control group, the expression levels of H1R, H2R, and H4R were significantly in-creased in experimental group (P＜0.05). Mast cells diffused interstitial bladder infiltrates (P＜0.05). There was no signifi-cant difference in the expression of H3R in two groups. Conclusion Mast cells, H1R, H2R, and H4R are closely related to the ketamine-induced cystitis, which may be new diagnostic indicators and new treatment targets of ketamine-induced cysti-tis.