5-羟色胺_(2A)受体拮抗剂减轻糖尿病肾病的实验研究  

Effects of 5-HT_(2A) receptor antagonist ketanserin on diabetic nephropathy in rats

作　　者：李晔[1] 甘卫华[2] 王晓颖[1] 储谦[1] 

机构地区：[1]上海第二医科大学附属瑞金医院病理科,上海200025 [2]南京医科大学小儿肾脏病研究所

出　　处：《肾脏病与透析肾移植杂志》2002年第5期401-406,共6页Chinese Journal of Nephrology,Dialysis & Transplantation

摘　　要：目的 :研究 5 羟色胺2A(5 HT2A)受体拮抗剂 (酮色林 )对糖尿病肾病 (DN)病理损害的影响。　 方法 :对链脲佐菌素诱导糖尿病大鼠模型 ,给予酮色林 1mg/ (kg·d)分别治疗 4周和 19周 ,用免疫酶标法检测α SMA肾小球系膜细胞的表达 ,免疫荧光染色和激光扫描共聚焦显微镜定量分析系膜区基质胶原Ⅳ蛋白 ,计算机病理图像分析系统定量检测肾小球面积、系膜区面积 ,RT PCR半定量测定肾小球TGF - β1mRNA的表达。 　结果 :与糖尿病未治疗组相比 ,酮色林治疗组第 4周时肾小球系膜细胞α SMA表达显著降低 ,第 19周时肾小球面积、系膜区占肾小球面积的比值以及系膜区胶原Ⅳ的含量及肾小球TGF β1mRNA的表达显著低于未治疗组。　 结论 :酮色林能抑制系膜细胞的活化及过度合成胶原Ⅳ ,减轻糖尿病大鼠肾小球肥大和系膜区扩张 ,抑制TGF - β1过度表达 。Objective:5- hydroxytryptamine(5 HT) has been proposed to be involved in the development of diabetic nephropathy.In this study,we investigated the effects of 5 HT 2A receptor antagonist(ketanserin) on diabetic rats with nephropathy.Methodology:Diabetes was induced in SD rats by intraperitoneal injection of STZ[65 mg/(kd·d)].The diabetic rats were randomly divided into treatment group (group K) and non treatment group (group D),and normal rats without diabetes were used as the control.Diabetic rats in group K received ketanserin [1 mg/(kg·d)] by gavages for 4 or 19 weeks,respectively.Relative kidney weight (kidney weight/body weight),blood glucose,24 hour urine protein and creatinine clearance rate(Ccr) were measured.Glomerular pathology was investigated by using computer morphometric image analysis system.Immunohistochemical staining was employed to assess the activation of mesangial cells by examining the expression of α SMA.Semiquantitative RT PCR was employed to determine TGF β1 mRNA in the isolated glomeruli.Type Ⅳ collagen in the mesangium was detected by immunofluorescent assay and quantified by laser scanning confocal microscopy. Results:In group D,all above biochemical parameters,TGF β 1 mRNA levels and glomerular surface area were increased significantly then in group C,while quantity of type Ⅳ collagen and the ratio of mesangial surface area/glomerular surface area (MSA/GSA) were merely increased at 19th week,however overexpression of α SMA in MC only be observed at 4th week.Comparing with group D,expression of α SMA was significantly suppressed in group K at 4th week.Ketanserin treatment also diminished glomerular surface area,the ratio of MSA/GSA and quantity of type Ⅳ collagen in mesangium at 19th week,with decreasing glomerular TGF β 1 mRNA levels ( P <0 05, P <0 01). Conclusion:Antagonist of 5 HT 2A receptor ketanserin can ameliorate diabetic nephropathy by inhibiting the activation of mesangial cells at its early stages,inhibiting the glomerular hyper

关 键 词：5-HT受体拮抗剂 糖尿病肾病 实验研究 治疗 

分 类 号：R587.2[医药卫生—内分泌] R977.15[医药卫生—内科学]