内质网应激相关凋亡分子在慢性肾衰竭大鼠中的表达及芪泽汤的干预作用.docVIP

内质网应激相关凋亡分子在慢性肾衰竭大鼠中的表达及芪泽汤的干预作用 暨南大学2009 级硕士学位论文 中文摘要 目的 采用腺嘌呤致大鼠肾损伤模型,观察内质网应激相关凋亡分子 CHOP 和 caspase-12 在肾内的表达情况以及中药的干预作用 , 探讨芪泽汤对慢性肾功能衰 竭CRF 大鼠内质网应激ERS 相关凋亡分子表达的影响,为中药治疗 CRF 提供 实验基础。 方法 腺嘌呤250mg/kg/d 灌胃24d 建立SD 大鼠肾衰模型。分为5 组:正常组、 模型组、尿毒清组 (2.5g/kg/d ) 、芪泽汤高剂量组 (50.4g/kg/d ) 、低剂量组 (12.6g/kg/d ) ,每组10 只。造模同时各治疗组 灌胃给药,干预24d 后,观察体 重变化,全自动生化分析仪检测大鼠血尿素氮(BUN ) 、血肌酐(Scr ) ,应用脱 氧核糖核普酸末端转移酶介导的缺口末端标记法(TUNEL )检测肾组织细胞凋 亡, 免疫印迹 (Western blot ) 检测 C/EBP 同源蛋白 CHOP 和半胱氨酸天冬氨酸 蛋白酶12(Caspase-12 )肾内表达水平。 结果 1 模型组BUN 、Scr 较对照组明显升高P 0.01 ; 2 TUNEL 结果显示空白组肾小管上皮细胞有少量凋亡,而模型组细胞凋 亡数明显增多P 0.01 ; 3 模型组CHOP ,Caspase-12 表达显著增强P 0.01 。芪泽汤低剂量和尿 毒清能抑制慢性肾功能衰竭大鼠肾小管上皮细胞凋亡和 CHOP 、 Caspase-12 表达 与模型组相比较P 0.05 。 结论 芪泽汤低剂量能保护腺嘌呤导致的大鼠肾损害, 减缓慢性肾衰的发展, 可能 与其抑制ERS 相关凋亡分子CHOP ,Caspase-12 高表达有关。 关键词: 内质网应激;慢性肾功能衰竭;芪泽汤;凋亡 I暨南大学2009 级硕士学位论文 Abstract Objective To establish renal damaged model by the adenine ,then observe the expression of CHOP C/EBP-homologous protein and Caspase-12,and the affects after the Chinese herbal compound into stomach. To study the effect of Qize decoction at Endoplasmic reticulum stress (ERS in rats with Chronic renal failureCRF,to provide experimental evidence for the clinical. Methods SD rats were fed with adenine of 2.5% to establish chronic renal failure model.They were divided into five groups :normal group, model group, Niaoduqing group (2.5g/kg/d ), Qize decoction of high dosage (50.4 g/kg/d )group and Qize decoction of low dosage (12.6 g/kg/d ) group ,each group has 10 rats.All groups were infused with adenine into stomach in addition to normol group, at the same time ,each rat in Chinese herbal compound group was also infused with Chinese herbal compound into stomach and niaoduqing group was given niaoduqing liquid for 24 days.Body weight were observed dynamically,BUN and SCr were checked by Automatic biochemical analyzer.The apoptosis of renal was evaluated by means of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling TUNEL.The e